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Abstract Background Parkinson’s disease is the second most common age-related neurodegenerative disease after Alzheimer’s. Pathogenic factors in Parkinson’s include inflammation and oxidative stress, which lead to dopaminergic cell apoptosis. The case–control study aims to determine the expression level of long non-coding RNAs (lncRNAs) of the apoptosis pathway in Parkinson’s patients compared to healthy individuals. In the case–control study, 50 patients with Parkinson’s disease were examined, along with 50 healthy individuals matched in age and sex. In both groups, the expression of long non-coding RNAs, including taurine upregulated 1 (TUG1), metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), nuclear-enriched abundant transcript 1 (NEAT1), and growth arrest-specific 5 (GAS5), was compared using real-time polymerase chain reaction (PCR). Results The ratio of MALAT1, NEAT1, and TUG1 gene expression in the case group was statistically significantly higher than in healthy individuals. The ratio of GAS5 gene expression in people with Parkinson’s disease was lower, with a statistically significant difference. The ratio of HULC gene expression was higher in the case group, but it did not show a statistically significant difference with the control group. Conclusion The involvement of long lncRNAs that increase apoptosis may play a role in the pathogenesis of the disease, which may be used for identification and therapeutic purposes.

Abstract Autism spectrum disorder (ASD) is a pervasive neurodevelopmental condition characterized by social interaction deficits, communication impairments, repetitive behaviors, and sensory sensitivities. While the etiology of ASD is multifaceted, abnormalities in glutamatergic neurotransmission and synaptic plasticity have been implicated. This study investigated the role of metabotropic glutamate receptor 8 (mGlu8) in modulating long-term potentiation (LTP) in a rat model of ASD induced by prenatal valproic acid (VPA) exposure. To induce an animal model with autism-like characteristics, pregnant rats received an intraperitoneal injection of 500 mg/kg of sodium valproate (NaVPA) on embryonic day 12.5. High-frequency stimulation was applied to the perforant path-dentate gyrus (PP-DG) synapse to induce LTP, while the mGlu8 receptor agonist (S)-3,4-dicarboxyphenylglycine (DCPG) was administered into the DG. The results revealed that VPA-exposed rats exhibited reduced LTP compared to controls. DCPG had contrasting effects, inhibiting LTP in controls and enhancing it in VPA-exposed rats. Moreover, reduced social novelty preference index (SNPI) in VPA-exposed rats was reversed by intra-DG administration of S-3,4-DCPG. In conclusion, our study advances our understanding of the complex relationship between glutamatergic neurotransmission, synaptic plasticity, and VPA-induced autism model. The findings suggest that mGlu8 receptor dysfunction plays a role in the impaired synaptic plasticity seen in ASD.

The precise cause of autism spectrum disorder (ASD) is not fully understood. Despite the involvement of glutamatergic dysregulation in autism, the specific contribution of mGlu4 receptors to synaptic plasticity remains unclear. Using the positive allosteric modulator VU0155041, we aimed to restore long-term potentiation (LTP) in the perforant path-dentate gyrus (PP-DG) pathway in VPA-induced autistic rat model. High-frequency stimulation was applied to the PP-DG synapse to induce LTP, while the VU0155041 was administered into the DG. Unexpectedly, VU0155041 failed to alleviate the observed LTP reduction in VPA-exposed rats, further resulting in a significant decrease in population spike LTP. This unexpected outcome prompts discussion on the complex nature of mGlu4 receptor modulation, highlighting potential interference with physiological processes underlying synaptic plasticity.

Traumatic brain injury (TBI) is a significant contributor to global mortality and disability, and there is still no specific drug available to treat cognitive deficits in survivors. Vanillic acid (VA), a bioactive phenolic compound, has shown protective effects in various models of neurodegeneration; however, its impact on TBI outcomes remains elusive. Therefore, this study aimed to elucidate the possible role of VA in ameliorating TBI-induced cognitive decline and to reveal the mechanisms involved. TBI was induced using the Marmarou impact acceleration model to deliver an impact force of 300 g, and treatment with VA (50 mg/kg; P.O.) was initiated 30 minutes post-TBI. The cognitive performance, hippocampal long-term potentiation (LTP), oxidative stress markers, neurological function, cerebral edema, and morphological changes were assessed at scheduled points in time. TBI resulted in cognitive decline in the passive avoidance task, impaired LTP in the perforant path-dentate gyrus (PP-DG) pathway, increased hippocampal oxidative stress, cerebral edema, neurological deficits, and neuronal loss in the rat hippocampus. In contrast, acute VA administration mitigated all the aforementioned TBI outcomes. The data suggest that reducing synaptic plasticity impairment, regulating oxidative and antioxidant defense, alleviating cerebral edema, and preventing neuronal loss by VA can be at least partially attributed to its protection against TBI-induced cognitive decline.

Background: Alzheimer’s disease (AD) is a progressive neurological disorder characterized by a wide range of cognitive and non-cognitive impairments. The present study was designed to investigate the potential effects of cacao on cognitive and non-cognitive performance and to identify the role of oxidative stress in an AD animal model induced by unilateral intracerebroventricular (U-ICV) injection of amyloid beta 1-42 (Aβ 1-42 ). Methods: Oral administration of cacao (0.5 g/kg/day) was performed for 60 consecutive days. Following 60 days, the open-field (OF) test, elevated plus-maze (EPM) test, novel object recognition (NOR) test, Barnes maze (BM) test, and Morris water maze (MWM) test were used to evaluate locomotor activity, anxiety-like behavior, recognition memory, and spatial memory, respectively. Total oxidant status (TOS) and total antioxidant capacity (TAC) in plasma were also examined. Furthermore, the number of healthy cells in the hippocampus’s dentate gyrus (DG), CA1, and CA3 regions were identified using hematoxylin and eosin staining. Results: The results indicated that the injection of Aβ 1-42 in rats led to recognition memory and spatial memory impairments, as well as increased anxiety. This was accompanied by decreased total antioxidant capacity (TAC), increased total oxidative stress (TOS), and increased neuronal death. Conversely, cacao treatment in AD rats improved memory function, reduced anxiety, modulated oxidative stress balance, and decreased neuronal death. Conclusion: The findings suggest that cacao’s ability to improve the balance between oxidants and antioxidants and prevent neuronal loss may be the mechanism underlying its beneficial effect against AD-related cognitive and non-cognitive impairments.

This study investigated the efficacy of p-coumaric acid (p-CA), a natural phenolic compound, on traumatic brain injury (TBI)-induced spatial cognitive deficits and the possible involved mechanisms. Rats received p-CA (100 mg/kg, orally) 30 min after diffuse TBI induction. Spatial memory, neuroplasticity, oxidative stress, and histological alterations were evaluated at scheduled time points. TBI reduced spatial memory capacity on days 1, 3, and 7 in the water-maze task, which was associated with suppressed hippocampal long-term potentiation (LTP) at the perforant path-dentate gyrus (PP-DG) synapses. These deficits were accompanied by the inhibition of the activities of antioxidant enzymes and the promotion of lipid peroxidation in the hippocampal and cerebral cortex areas. Moreover, TBI resulted in neuronal loss in the DG. Interestingly, p-CA treatment ameliorated all the above-mentioned TBI outcomes. The findings demonstrate that p-CA alleviates TBI-induced spatial cognitive impairment, possibly by mitigating hippocampal synaptic dysfunction, modulating oxidative-antioxidative status, and preventing neuronal loss.

Vitamin B (Vit B) plays a regulatory role in cognitive memory and learning. We examined the biochemical and behavioral effects of biotin supplementation (BS) and swimming training (ST) on Alzheimer's disease (AD), the most common type of dementia, in male rats. Sixty rats were randomly assigned to six groups: control, sham (receiving phosphate-buffered saline), AD (receiving a single injection of Aβ into the lateral ventricle), ST (for 28 days and before Aβ injection), and BS (receiving BS through oral gavage for 28 days before Aβ injection). The treatments were continued until the end of the behavioral tests. Learning and memory functions were investigated through the Morris water maze (MWM) and depression and anxiety-like behaviors were tested by elevated plus-maze (EPM) and forced swimming tests. In addition, oxidative stress biomarkers, such as total thiol groups (TTG) and malondialdehyde (MDA) in serum were assessed and histological studies were performed using brain tissues. In the AD group, Aβ increased the distance traveled and escape latency in the MWM, but co-administration of BS and ST attenuated the results of the MWM, EPM, and FST tests. Furthermore, BS decreased the litigious biochemical effects of Aβ by enhancing the levels of TTG, in addition to reducing serum MDA levels. The use of BS as a potent antioxidant improved Aβ-induced memory impairment. It attenuated oxidative stress biomarkers in the brain (number of Aβ plaques) and serum of AD rats. We provide evidence for the use of BS in neurodegenerative disorders, such as AD, to elucidate the possible mechanisms.

Abstract Background Alzheimer's disease (AD) is a complex and common neurodegenerative disorder. The present study aimed to investigate the potential effects of selegiline (SEL) on various aspects of memory performance, anxiety, and oxidative stress in an AD rat model induced by intracerebroventricular injection of amyloid beta1‐42 (Aβ1‐42). Methods Oral administration of SEL at a dose of 0.5 mg/kg/day was performed for 30 consecutive days. Following the 30 days, several tests, including the open‐field, elevated plus‐maze, novel object recognition, Morris water maze, and passive avoidance learning were conducted to assess locomotor activity, anxiety‐like behavior, recognition memory, spatial memory, and passive avoidance memory, respectively. Results The results indicate that the induction of AD in rats led to recognition memory, spatial memory, and passive avoidance memory impairments, as well as increased anxiety. Additionally, the AD rats exhibited a decrease in total antioxidant capacity and an increase in total oxidant status levels, suggesting an imbalance in oxidative‐antioxidant status. However, the administration of SEL improved memory performance, reduced anxiety, and modulated oxidative‐antioxidant status in AD rats. Conclusions These findings provide evidence that SEL may alleviate anxiety‐like behavior and cognitive deficits induced by Aβ through modulation of oxidative‐antioxidant status.

There is growing evidence that the hippocampus comprises diverse neural circuits that exhibit longitudinal variation in their properties, however, the intermediate region of the hippocampus has received comparatively little attention. Therefore, this study was designed to compared short- and long-term synaptic plasticity between the dorsal and intermediate regions of the hippocampus in normal and PTZ-kindled rats. Short-term plasticity was assessed by measuring the ratio of field excitatory postsynaptic potentials’ (fEPSPs) slope in response to paired-pulse stimulation at three different inter-pulse intervals (20, 80, and 160 ms), while long-term plasticity was assessed using primed burst stimulation (PBS). The results showed that the basal synaptic strength differed between the dorsal and intermediate regions of the hippocampus in both control and kindled rats. In the control group, paired-pulse stimulation of Schaffer collaterals resulted in a significantly lower fEPSP slope in the intermediate part of the hippocampus compared to the dorsal region. Additionally, the magnitude of long-term potentiation (LTP) was significantly lower in the intermediate part of the hippocampus compared to the dorsal region. In PTZ-kindled rats, both short-term facilitation and long-term potentiation were impaired in both regions of the hippocampus. Interestingly, there was no significant difference in synaptic plasticity between the dorsal and intermediate regions in PTZ-kindled rats, despite impairments in both regions. This suggests that seizures eliminate the regional difference between the dorsal and intermediate parts of the hippocampus, resulting in similar electrophysiological activity in both regions in kindled animals. Future studies should consider this when investigating the responses of the dorsal and intermediate regions of the hippocampus following PTZ kindling.

Abstract Plasticity is a common feature of synapses that is stated in different ways and occurs through several mechanisms. The regular action of the brain needs to be balanced in several neuronal and synaptic features, one of which is synaptic plasticity. The different homeostatic processes, including the balance between excitation/inhibition or homeostasis of synaptic weights at the single-neuron level, may obtain this. Homosynaptic Hebbian-type plasticity causes associative alterations of synapses. Both homosynaptic and heterosynaptic plasticity characterize the corresponding aspects of adjustable synapses, and both are essential for the regular action of neural systems and their plastic synapses. In this review, we will compare homo- and heterosynaptic plasticity and the main factors affecting the direction of plastic changes. This review paper will also discuss the diverse functions of the different kinds of heterosynaptic plasticity and their properties. We argue that a complementary system of heterosynaptic plasticity demonstrates an essential cellular constituent for homeostatic modulation of synaptic weights and neuronal activity. Graphical Abstract

Introduction: Alzheimer’s disease (AD) causes progressive loss of cognitive function and synaptic plasticity, which is the most common form of dementia. The present study was designed to scrutinize the effects of cacao on passive avoidance memory function and to identify the roles of hippocampal synaptic plasticity and oxidative stress in an AD rat model induced by unilateral intracerebroventricular (UICV) injection of amyloid-beta (Aβ).Methods: Oral administration of cacao (500 mg/kg/ day) was given for 2 consecutive months. A memory retention test was conducted 24 h after passive avoidance training was completed. Subsequently, the amplitude of population spike (PS) and slope of field excitatory postsynaptic potentials (fEPSPs) were assessed at hippocampal long-term potentiation (LTP) in perforant pathway–dentate gyrus (PP-DG) synapses. Moreover, total thiol group (TTG) and malondialdehyde (MDA) concentrations were evaluated in the plasma. Furthermore, compact Aβ plaques were detected in the hippocampal DG by performing Congo red staining.Results: As a result of AD induction, passive avoidance memory was impaired; also, reduced fEPSP slopes, PS amplitudes, and content of TTG, and increase in MDA levels in the rats were observed. In contrast, cacao treatment ameliorated passive avoidance memory impairment, improved hippocampal LTP impairment, modulated oxidative–antioxidative status, and delayed Aβ plaques production in AD rats.Disscussion: Conclusively, cacao alleviates Aβ-induced cognitive deficit, probably by the amelioration of hippocampal LTP impairment, modulation of oxidative–antioxidative status, and inhibition of Aβ plaque accumulation

Menopause may increase the risk of Alzheimer’s disease (AD) dementia. This study aimed to use young plasma therapy (YPT) to improve dementia caused by AD in aged ovariectomized rats. Female Wistar rats were used in the following groups: (a) young (CY) (180–200 g, 2–3 months, n = 10) and (b) old groups (250–350 g, 22–24 months, n = 60). The old rats were randomly assigned to six sub-groups: (1) control, (2) sham, (3) ovariectomized group (OVX), (4) OVX + Alzheimer disease (OVX + AD), (5) OVX + AD+ 17β-Estradiol (OVX + AD + E), and (6) OVX + AD + young plasma (OVX + AD + YP). Cognitive behaviors were evaluated using NOR, MWM, and PAL tests. MiR-134a, SIRT-1, CREB, and BDNF expressions were measured using real-time PCR and western blot, respectively. Oxidative stress in hippocampal tissue was assayed using ELISA kits. OVX and AD caused significant cognitive impairment (p < 0.001), up-regulated miR-134a (p < 0.001), down-regulated SIRT-1, CREB, and BDNF protein expression (p < 0.001), and decreased antioxidant marker levels (p < 0.001) compared to the sham group. YPT significantly restored miR-134a (p < 0.001), SIRT-1 (p < 0.001), CREB (p < 0.001), and BDNF (p < 0.001) protein expression in OVX + AD rats. YPT, as much as or more than estrogen therapy (ERT), significantly improved oxidative stress and down-regulated miR-134a expression and the up-regulation of SIRT-1, CREB, and BDNF proteins in OVX + AD rats (p < 0.001). YPT significantly improved histological alteration compared to the OVX + AD group (p < 0.001). As a non-pharmacological treatment, YPT can improve the expression of miR-134a and SIRT-1, CREB, and BDNF proteins as much as or more than estrogen therapy, ameliorating AD-induced dementia in aged OVX rats.

Abstract Background Vinpocetine (Vin) is known as a phosphodiesterase 1 inhibitor (PDE1-I) drug with multilateral effects, including antioxidant and anti-inflammatory activity. In this research, we investigated the neuroprotective and therapeutic effects of Vin through hippocampal synaptic plasticity on a rat’s model of Alzheimer’s disease (AD) induced by an intracerebroventricular (ICV) injection of beta-amyloid (Aβ). Methods Sixty adult male Wistar rats were randomly divided into six groups: 1. control, 2. sham, 3. Aβ, 4. pretreatment (Vin + Aβ): Vin (4 mg/kg, gavage) for 30 days and then, inducing an AD model by an ICV injection of Aβ(1–42), 5. treatment (Aβ + Vin): inducing an AD model and then receiving Vin for 30 days by gavage, and 7. pretreatment + treatment (Vin + Aβ + Vin): receiving Vin by gavage for 30 days before and 30 days after the induction of an AD model. After these procedures, via stereotaxic surgery, the stimulating electrodes were placed at the perforant pathway (PP) and the recording electrodes were implanted in the dentate gyrus. Results Excitatory postsynaptic potential (EPSP) slope and population spike (PS) amplitude in the Aβ group meaningfully diminished compared to the control group after the induction of long-term potentiation (LTP). Conclusions Vin could significantly prevent the Aβ effects on LTP. It can be concluded that pretreatment and treatment with Vin can be neuroprotective against harmful consequences of Aβ on hippocampal synaptic plasticity.

Abstract Background The release of various neurotransmitters and thereby the excitability of neuronal circuits are regulated by the endocannabinoid system in an activity-dependent manner. Hippocampal long-term potentiation (LTP) is augmented in cannabinoid type 1 (CB1) receptor-deficient mice. CB1 receptors exist on GABAergic axon terminals in the hippocampus. In our previous work, we showed that CB1 antagonists increased the population spike (PS) amplitude, field excitatory post-synaptic potential (fEPSP), and the LTP induction in the dentate gyrus (DG) of the rat hippocampus while the GABAB antagonist decreased these parameters. Determining the underlying mechanisms of the pre- and/or postsynaptic locus of LTP expression is of great importance. In this study, we investigated whether LTP alteration acutely caused by CB1 and GABAB receptor antagonists (AM251 and CGP55845, respectively) happens at the postsynaptic or presynaptic regions, or at both. Therefore, the paired-pulse ratio (PPR) was assessed prior to and following the LTP induction in the studied groups. Methods Male Wistar rats were randomly assigned to the groups of control, AM251, CGP55845, CGP55845 + AM251. A high-frequency stimulation (HFS) of the perforant path (PP) was used to induce LTP in the DG region. Results Statistical analysis revealed that AM251 produced significant increase in excitatory postsynaptic potential (EPSP) slope and amplitude of PS. Conversely, administration of CGP55845 produced decrease in slope of EPSP. The current results indicated that the PPR was not influenced by LTP induction in the presence of AM251 or CGP55845 either alone or their combination. Conclusions It can be concluded that the site causing LTP expression is, at least in part, the postsynaptic site because PPR was not influenced by LTP induction in the presence of AM251 or CGP55845 either alone or their combination.

Neurological diseases affect the nervous system, including the brain, spinal cord, cranial nerves, nerve roots, autonomic nervous system, neuromuscular junctions, and muscles. Herbal medicine has long been used to cure these diseases. One of these plants is lavender, which is composed of various compounds, including terpenes, such as linalool, limonene, triterpenes, linalyl acetate, alcohols, ketones, polyphenols, coumarins, cineole, and flavonoids. In this review, the literature was searched using scientific search engines and databases (Google Scholar, Science Direct, Scopus, and PubMed) for papers published between 1982 and 2020 via keywords, including review, lavender, and neurological disorders. This plant exerts its healing effect on many diseases, such as anxiety and depression through an inhibitory effect on GABA. The anti-inflammatory effects of this plant have also been documented. It improves depression by regulating glutamate receptors and inhibiting calcium channels and serotonergic factors, such as SERT. Its antiepileptic mechanism is due to an increase in the inhibitory effect of GABA and potassium current and a decrease in sodium current. Therefore, many vegetable oils are also used in herbal medicine. In this review, the healing effect of lavender on several neurological disorders, including epilepsy, depression, anxiety, migraine, and Alzheimer’s disease was investigated. All findings strongly support the traditional uses of lavender. More clinical studies are needed to investigate the effect of the plants’ pharmacological active constituents on the treatment of life-threatening diseases in humans. The limitations of this study are the low quality and the limited number of clinical studies. Different administration methods of lavender are one of the limitations of this review.

Introduction: Brain abilities decrease after brain stroke in elderly. The neuroprotective effect of exercise training has been proved in clinical trials and animal experiment. Nevertheless, it is not still clear what kind of exercise has greater protective effect. The present study aimed at investigating pre-conditioning effect of endurance, resistance, and concurrent training on learning ability, anxiety, and spatial memory in aged rats following stroke strength with middle cerebral artery occlusion. Method: We used 50 male Wistar rats (age = 24 months) that were assigned randomly in five groups; 1: sham group, 2: Control group 3: Endurance training 4: Resistance training, and 5: concurrent training. The exercise training groups received training for four weeks. Following training, middle cerebral artery occlusion was applied to induce cerebral ischemia. Using the elevated plus maze, shuttle box test, and Morris water maze, neurocognitive functions were tested in the sample rats. Results: It was found that resistance training did not affect spatial memory in the acquisition phase, while concurrent training and endurance training enhanced spatial memory in the acquisition phase. On the contrary, spatial memory was improved by resistance training in the retention phase, while concurrent and endurance exercises did not affect spatial memory in the retention phase. Passive avoidance learning ability at acquisition phase was more in resistance group compared to the endurance and concurrent training in shuttle box test, but in retention phase was similar between training groups. Unlike endurance and concurrent training, resistance training reduced anxiety in senescent rats. Conclusion: All three exercise types alleviated aversive learning and memory impairment induced by stroke in senescent rats. Notably, the resistance training showed a greater protective effect compared to the other two training methods.

Neurological disorders affect the nervous system. Biochemical, structural, or electrical abnormalities in the spinal cord, brain, or other nerves lead to different symptoms, including muscle weakness, paralysis, poor coordination, seizures, loss of sensation, and pain. There are many recognized neurological diseases, like epilepsy, Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), stroke, autosomal recessive cerebellar ataxia 2 (ARCA2), Leber's hereditary optic neuropathy (LHON), and spinocerebellar ataxia autosomal recessive 9 (SCAR9). Different agents, such as coenzyme Q10 (CoQ10), exert neuroprotective effects against neuronal damage. Online databases, such as Scopus, Google Scholar, Web of Science, and PubMed/MEDLINE were systematically searched until December 2020 using keywords, including review, neurological disorders, and CoQ10. CoQ10 is endogenously produced in the body and also can be found in supplements or foods. CoQ10 has antioxidant and anti-inflammatory effects and plays a role in energy production and mitochondria stabilization, which are mechanisms, by which CoQ10 exerts its neuroprotective effects. Thus, in this review, we discussed the association between CoQ10 and neurological diseases, including AD, depression, MS, epilepsy, PD, LHON, ARCA2, SCAR9, and stroke. In addition, new therapeutic targets were introduced for the next drug discoveries.

Considerable scientific evidence suggests that the intrauterine environment plays a crucial role in determining the long-term health of offspring. The present study aims to investigate the effects of high-intensity interval training in maternal rats before and during pregnancy on the antioxidant status, mitochondrial gene expression, and anxiety-like behavior of their offspring. A total of thirty-two female rats were assigned to four maternal groups based on the timing of exercise: before pregnancy, before and during pregnancy, during pregnancy, and sedentary. The female and male offspring were allocated to groups that matched their mothers’ exercise regimen. Anxiety-like behavior in the offspring was evaluated using the open-field and elevated plus-maze tests. Our findings indicate that maternal HIIT does not have any detrimental effect on the anxiety-related behavior of offspring. Also, maternal exercise before and during pregnancy could improve the general activity of the offspring. Furthermore, our results demonstrate that female offspring exhibit more locomotion activity than males. Besides, maternal HIIT leads to a reduction in the levels of TOS and MDA, while TAC levels increase, and significantly upregulate the gene expression of PGC1-α, NFR1, and NRF2 in both sexes in the heart. Therefore, our study suggests that maternal HIIT is a beneficial maternal behavior and serves as a cardioprotective agent to enhance the health of the next generations.

Background and purpose: The harmful effects of morphine on the liver after withdrawal syndrome are unclear. In this experiment, we investigated the effects of exercise on oxidative stress, liver inflammation, liver enzymes, and liver histology after morphine withdrawal in rats. Materials and methods: In this experimental study, male Wistar rats (n=30) were randomly divided into five groups: ‎‎control, withdrawal syndrome (addicted), withdrawal syndrome+‎endurance training, withdrawal syndrome+‎resistance training, withdrawal syndrome+concurrent training. The experimental groups received morphine for 28 days, and after withdrawal, training interventions were done for 10 weeks. At the end of the study, the rats were sacrificed and liver was removed. Antioxidant activity ‎was measured and histopathological evaluation of ‎liver was done. Also, the TNF-α levels were determined.‎ Results: Compared with control rats, the levels of total antioxidant capacity (TAC), and the activities of glutathione and superoxide dismutase (SOD) significantly decreased in morphine withdrawal group (P

The study of exercise preconditioning can develop strategies to prevent cardiovascular diseases and outline the efficient exercise model. However, the exercise type with the most protective effect against ischemia-reperfusion injury is unknown. In this study, we examined the effects of three kinds of exercise preconditioning on myocardial ischemia-reperfusion in adult rats and explored the possible underlying mechanisms. Male Wistar rats subjected to ten weeks of endurance, resistance, and concurrent training underwent ischemia (30 min) and reperfusion (120 min) induction. Then, infarction size, serum levels of the CK-MB, the redox status, and angiogenesis proteins (VEGF, ANGP-1, and ANGP-2) were measured in the cardiac tissue. Results showed that different exercise training modes have the same reduction effects on infarction size, but ischemia-reperfusion-induced CK-MB was lower in response to endurance training and concurrent training. Furthermore, cardiac VEGF levels increased in all three kinds of exercise preconditioning but ischemia-reperfusion-induced ANGP-1 elevated more in endurance training. The cardiac GPX activity was improved significantly through the resistance and concurrent exercise compared to the endurance exercise. In addition, all three exercise preconditioning models decreased MPO levels, and ischemia reperfusion-induced MDA was lower in endurance and resistance training. Overall, these results indicated that cardioprotection of exercise training against ischemia-reperfusion injury depends on the exercise modality. Cardioprotective effects of aerobic, resistance, and concurrent exercises are due to different mechanisms. The preconditioning effects of endurance training are mediated mainly by pervasive angiogenic responses and resistance training through oxidative stress amelioration. The preconditioning effects of concurrent training rely on both angiogenesis and oxidative stress amelioration.

Lead (Pb) is a highly poisonous environmental pollutant that can induce cognitive decline. Chrysin, a natural flavonoid compound, has anti-oxidative, anti-inflammatory, and neuroprotective properties in different neurodegenerative disorders. The present study was designed to examine the putative effects of chrysin against Pb-induced cognitive impairment and the possible involved mechanisms. Adult male Wistar rats were exposed to Pb acetate (500 ppm in standard drinking water) either alone or in combination with daily oral administration of chrysin (30 mg/kg) for eight consecutive weeks. During the eight-week period of the study, the cognitive capacity of the rats was evaluated by employing both novel object recognition and passive avoidance tests. On day 56, hippocampal synaptic plasticity (long-term potentiation; LTP) was recorded in perforant path-dentate gyrus (PP-DG) synapses to assess field excitatory postsynaptic potentials (fEPSPs) slope and population spike (PS) amplitude. Subsequently, pro- and anti-inflammatory cytokines and histological changes were evaluated in the cerebral cortex and hippocampus of the rats. Moreover, Pb levels in blood and brain tissues were assessed. The results showed that Pb exposure causes cognitive decline, inhibition of hippocampal LTP induction, imbalance of pro- and anti-inflammatory cytokines, enhancement of Pb levels in blood and brain tissues, and neuronal loss. However, chrysin treatment improved cognitive dysfunction, ameliorated hippocampal LTP impairment, modulated inflammatory status, reduced Pb concentration, and prevented neuronal loss in the Pb-exposed rats. The results suggest that chrysin alleviates Pb-induced cognitive deficit, possibly through mitigation of hippocampal synaptic dysfunction, modulation of inflammatory status, reduction of Pb concentration, and prevention of neuronal loss.

Background: Learning and memory may decline due to Alzheimer’s disease (AD) in older adults. A reduction in cyclic guanosine monophosphate concentration and an increase in phosphodiesterase activity have been reported in the process of aging. Althoughphosphodiesterase (PDE) type 5 inhibitor, Tadalafil is used to treat erectile dysfunction; PDE inhibitors possibly prevent cognition impairment in aging. This study was designed to investigate the effects of tadalafil on memory in middle-aged and young healthy and AD rats. Methods: Memory impairment was induced by intracerebroventricular (ICV) administration of streptozotocin (STZ; 3 mg/kg) in AD rats. Male Wistar rats (middle-aged and young) were distributed into six groups as follows: two control, two AD, and two AD+tadalafil (1 mg/kg)groups. Saline or tadalafil was administered once a day orally for 40 consecutive days. Animals were tested using novel object recognition (NOR), passive avoidance learning (PAL), and Morris water maze (MWM) tests. Results: Aged AD rats exhibited a significant impairment in cognition in the NOR test and impaired learning and memory in PAL and MWM tests compared with the control aged rats. Tadalafil treatment in aged AD rats significantly improved the discrimination index in the NORtest, decreased the time spent in the dark compartment in the PAL test, and increased time spent in the target quadrant in MWM tests compared with aged AD rats. In young AD rats, treatment with tadalafil significantly enhanced cognition, learning, and memory in the NOR, PAL, andMWM tests compared with young AD rats treated with saline. Conclusion: Tadalafil treatment in aged rats improves cognition and memory after STZ-induced(ICV) memory impairment. It can be concluded that chronic treatment with tadalafil is protective against cognitive, learning, and memory impairment in both young and aged subjects.

Oxidative stress plays an important role in the development of Alzheimer's disease (AD). The purpose of this study was to investigate the protective effects of lutein, a carotenoid with antioxidant functions, on memory and learning using behavioral methods in a rat model of AD. Beta-amyloid (Aβ) reduced passive avoidance learning (PAL), spatial and cognitive memory. On the other hand, lutein improved PAL, spatial memory in Morris water maze and Barnes maze tests, and cognitive memory in novel object recognition test. Levels of malondialdehyde (MDA) and total oxidant status (TOS) increased and total antioxidant capacity (TAC) decreased in the AD group, while in groups receiving lutein, MDA and TOS levels decreased and TAC increased. Lutein improves learning and memory that it is probably due to its antioxidant and neuroprotective properties. These results using an animal model are consistent with lutein as a potential therapeutic agent in the treatment and prevention of AD.

Introduction: Extremely Low-Frequency Electromagnetic Fields (ELF-EMFs) have gathered significant consideration for their possible pathogenicity. However, their effects on the nervous system’s functions were not fully clarified. This study aimed to assay the impact of ELF-EMFs with different intensities on memory, anxiety, antioxidant activity, β-amyloid (Aβ) deposition, and microglia population in rats. Methods: Fifty male adult rats were randomly separated into 5 groups; 4 were exposed to a flux density of 1, 100, 500, and 2000 microtesla (µT), 50 Hz frequency for one h/day for two months, and one group as a control group. The control group was without ELF-EMF stimulation. After 8 weeks, passive avoidance and Elevated Plus Maze (EPM) tests were performed to assess memory formation and anxiety-like behavior, respectively. Total free thiol groups and the index of lipid peroxidation were evaluated. Additionally, for detection of Aβ deposition and stained microglia in the brain, anti-β-amyloid and anti-Iba1 antibodies were used. Results: The step-through latency in the retention test in ELF-EMF exposure groups (100500 & 2000 µT) was significantly greater than the control group (P

Introduction: Hyperalgesia is among the current complications of diabetes mellitus; oxidative stress and inflammation were influential in its development. As an herbal component, Ellagic Acid (EA) has some biological activities, including antioxidant and anti-inflammatory effects. This study was designed to evaluate the possible beneficial effect of EA on hypernociception in Streptozotocin (STZ)-induced hyperglycemic rats. Methods: Forty-eight male Wistar rats were divided into the control (receiving vehicle), hyperglycemic, EA (25 mg/kg)-treated control, EA (50 mg/kg)-treated control, EA (25 mg/kg)-treated hyperglycemic, and EA (50 mg/kg)-treated hyperglycemic groups. Hyperglycemia was induced by a single Intraperitoneal (IP) injection of STZ (60 mg/Kg). EA was administered daily by oral gavage for four weeks. The nociceptive response was assessed using Tail-Flick (TF) and Hot-Plate (HP) tests. Also, oxidative stress markers, including Malondialdehyde (MDA), Total Oxidant Status (TOS), and Total Antioxidant Capacity (TAC) in the serum, were evaluated. Results: Hyperglycemic animals were found with significant changes, including a reduction in TF and HP latencies, an elevation in serum MDA level and TOS, and a decrease in serum TAC compared with controls. The treatment of hyperglycemic rats with EA facilitated the reduction of TF latency at the dose of 25 mg/kg and HP latency at 50 mg/kg. Furthermore, EA significantly increased TAC and decreased MDA level at a 50 mg/kg dose and reduced TOS at both doses in the serum of hyperglycemic animals. No significant alterations were found in the parameters studied in EA-treated normal rats. Conclusion: These results displayed the antinociceptive effect of EA in hyperglycemic rats via attenuating oxidative stress. Therefore, EA appears to be a promising agent for managing. Hyperglycemic hypernociception.

Abstract Background Recent studies show that gender may have a significant impact on brain functions. However, the reports of sex effects on spatial ability and synaptic plasticity in rodents are divergent and controversial. Here spatial learning and memory was measured in male and female rats by using Morris water maze (MWM) task. Moreover, to assess sex difference in hippocampal synaptic plasticity we examined hippocampal long-term potentiation (LTP) at perforant pathway-dentate gyrus (PP-DG) synapses. Results In MWM task, male rats outperformed female rats, as they had significantly shorter swim distance and escape latency to find the hidden platform during training days. During spatial reference memory test, female rats spent less time and traveled less distance in the target zone. Male rats also had larger LTP at PP-DG synapses, which was evident in the high magnitude of population spike (PS) potentiation and the field excitatory post synaptic potentials (fEPSP) slope. Conclusions Taken together, our results suggest that sex differences in the LTP at PP-DG synapses, possibly contribute to the observed sex difference in spatial learning and memory.

The present study was designed to determine the effects of p-coumaric acid (p-CA), a phenolic compound, on passive avoidance memory function and hippocampal long-term potentiation (LTP) in an Alzheimer's disease (AD) rat model induced by aluminum chloride (AlCl3). p-CA (100 mg/kg; P.O.) was administered concomitantly with AlCl3 (100 mg/kg; P.O.) for 42 consecutive days. Results of this study revealed an attenuation of memory capacity, which was accompanied by a reduction in both components of LTP (field excitatory postsynaptic potentials slope and population spike amplitude) and an increase in amyloid-beta (Aβ) plaques production in the AlCl3-exposed rats. Intriguingly, treatment with p-CA improved passive avoidance memory dysfunction, ameliorated hippocampal LTP impairment, and hindered Aβ plaque accumulation in the hippocampal dentate gyrus of AlCl3-treated rats. This data provides evidence that p-CA improves AlCl3-induced passive avoidance memory decline, which may be partly related to amelioration of synaptic dysfunction and suppression of Aβ plaque formation.

Hyperlipidemia affects a significant number of patients despite treatment with cholesterol-lowering drugs. Due to the low efficacy of synthetic drugs, there is a need for new agents with low side effects. Therefore, the effects of flaxseeds oil and animal omega-3 on the hyperlipidemic rats were investigated. Forty male Wistar rats were assigned to four groups (n = 10): 1) control group that was fed with a standard diet (pallets). 2) high-fat diet (HFD) control group that was fed with high-fat food for 42 days, 3) Omega-3 group that received HFD for 21 days, followed by HFD + omega-3 capsule (600 mg/kg; 21 days/gavage), and 4) flaxseed oil group that received HFD for 21 days, followed by HFD + flaxseed oil (10 ml/kg; 21 days/gavage). Blood samples were collected three times and at the stages one to third of the experiment from the rats’ tail. The results showed that high levels of fat significantly increased cholesterol, triglyceride (TG), and low-density lipoprotein (LDL) in the flaxseed, HFD control, and omega-3 groups in the second stages of the experiment. Inverse, omega-3 or flaxseed oil supplementation decreased cholesterol, TG, and LDL levels and increased high-density lipoprotein (HDL) level in comparison with the HFD control group in the third stages of the experiment. There was no significant difference in the studied parameters between the flaxseed- and omega-3-treated groups. It can be concluded that flaxseed oil similar to omega-3 is effective in the treatment of hyperlipidemia.

Abstract Background Several studies have shown that glutamate neurotransmission in the nucleus accumbens (NAc) is required for the development of morphine-induced conditional place preference (CPP). In addition, metabotropic glutamate receptors (mGluRs) in NAc play important roles in the reward pathways. However, the precise role of mGluR4 in different steps of the morphine-induced CPP is less well known. In the present study the effect of bilateral intra-accumbal infusion of VU0155041, as a specific mGluR4 agonist on the acquisition and expression of morphine induced CPP in male Wistar rats was investigated. The animals were bilaterally implanted with guide cannulae above the NAc. In the first step of the study, the VU0155041 was administered at doses of 10, 30 and 50 μg/0.5 μL saline per side into the NAc during the 3 days of morphine (5 mg/kg) conditioning (acquisition) phase of morphine-induced CPP. In the second step of the study, the rats bilaterally received VU0155041 at the dose of 50 μg/0.5 μL, 5 min before the post-conditioning test in order to check the effect of VU0155041 on the expression of morphine-induced CPP. Results The results showed that the intra-accumbal injection of VU0155041 inhibits the acquisition of morphine-induced CPP in a dose dependent manner, but had no effect on expression. Conclusions The data indicated that intra-NAc administration of VU0155041 dose dependently blocks the establishment of morphine-induced CPP and reduces the rewarding properties of morphine. These effects may be related to changes in glutamate activity in the NAC and/or learning dependent mechanism of glutamate neurotransmission in reward pathway(s).

Objective(s): Hypercholesterolemia is correlated with brain amyloid-β (Aβ) deposition and impaired cognitive functions and contributes to Alzheimer’s disease. Effects of cholesterol-lowering dill tablets and aqueous extract of Ocimum basilicum L. (basil) on learning and memory and hippocampus fatty acid composition were examined. mRNA levels of the genes involved in cholesterol homeostasis were also determined in high-cholesterol diet (HCD) fed rats. Materials and Methods: Forty male Wistar rats were allocated to 4 groups: rats fed chow diet (C); rats fed high-cholesterol (2%) diet (HCD); rats treated with HCD+300 mg/kg dill tablets (HCD+Dill); and finally, rats fed HCD and treated with 400 mg/kg basil aqueous extract (HCD+basil). Treatment was carried out for 16 weeks. Hippocampus Aβ(1-42) level was determined. Spatial and passive avoidance tests were used to examine cognitive functions. Hippocampal FA composition was assessed by gas chromatography. Basil aqueous extract was analyzed by GC-double mass spectroscopy (GC-MS/MS) and expression of LXR-α, LXR-β, and ABCA1 genes was assessed by qRT-PCR. Results: Dill tablets and basil extract remarkably ameliorated serum cholesterol (p

Background and objectives: Alzheimer's disease (AD) is characterized by progressive cognitive decline. Oxidative stress plays a central role in the pathogenesis of AD. It has been proposed that administration of antioxidants affect cognitive processes, such as learning and memory. This study investigated the protective effects of vitamin E and Ginkgo biloba extract (as antioxidants) on learning and memory, hippocampal plasticity, and apoptotic marker proteins in a rat model of AD. Methods: The hyroalcoholic extract of Gingko biloba leaves wasprepared using maceration method. Male Wistar rats were randomly divided into six groups: control, sham received intra-hippocampal injection (I.H.P) of vehicle, AD model that received intra-hippocampal injection of the beta-amyloid (Aβ), AD+ vitamin E (200 mg/kg, i.p.), AD+ G. biloba (100 mg/kg/p.o.), and AD+ vitamin E (200 mg/kg, i.p.)+ G. biloba (100 mg/kg/p.o.). At the end of the treatments, the rats were subjected to the passive avoidance learning (PAL) test. The field long wterm potentials (LTP) were recorded in the hippocampal dentate gyrus. Hippocampal expressions of Bax and Bcl-2 (as pro-apoptotic, as anti-apoptotic) proteins were measured by western blot method. Results: Treatment with G. biloba and vitamin E improved the Aβ-induced memory impairment in the PAL task. Vitamin E and/or G. biloba extract enhanced the population spike amplitude evoked potentials of the LTP components, vitamin E and/or G. biloba extract increased Bcl-2 expression and decreased Bax expression in the hippocampus. Conclusion: Ginkgo biloba and vitamin E could suppress the expression of apoptosis markers and improved hippocampal LTP impairment and the memory deficit induced by Aβ.

Background: Alzheimer Disease (AD) is an age-related neurodegenerative disorder with a progressive impairment of cognitive function. The pineal gland hormone melatonin (MEL) has been known as a protection agent against AD. However, the effect of melatonin in various doses is inconsistent. Objectives: In this study, we aimed to investigate two doses of MEL on learning and memory in the amyloid-βeta (Aβ)-induced AD in the rats. Materials & Methods: Forty-eight male Wistar rats were used in the experiment and randomly divided control, sham, vehicle, AD, AD+MEL10 mg/kg, and AD+MEL 20 mg/kg groups. Intracerebroventricular injection of Aβ1–42 was used to develop the animal model of AD. Also, MEL-treated groups received an intraperitoneal injection of MEL for 4 next weeks. The Morris Water Maze (MWM) and Passive Avoidance Learning (PAL) tests were used to examine animals’ learning and memory. The brain of animals was removed for immunohistochemistry for anti- Amyloid Precursor Protein (APP). Results: Intra-peritoneal injection of MEL significantly improve learning and memory in MWM (P=0.000) and PAL test (P=0.000), but there were no significant changes in the two groups that received the melatonin (P>0.05). Histopathological analysis revealed that the clearance of APP deposition in the AD+MEL20 group was considerable compared with the AD+MEL10 group (P=0.000). Conclusion: Our findings indicate that 10 and 20 mg/kg doses of melatonin have similar results on learning and memory in the AD model. But 20 mg/kg of melatonin has significantly more effect on the clearance of APP deposition.

Background and purpose: Kaempferol (KM), a flavonoid, has an anti-inflammatory and anticancer effect and prevents many metabolic diseases. Nonetheless, very few studies have been done on the antinociceptive effects of KM. This research aimed at assessing the involvement of opioids, gamma-aminobutyric acid (GABA) receptors, and inflammatory mediators in the antinociceptive effects of KM in male Wistar rats. Experimental approach: The intracerebroventricular and/or intrathecal administration of the compounds was done for examining their central impacts on the thermal and chemical pain by the tail-flick and formalin paw tests. For assessing the role of opioid and GABA receptors in the possible antinociceptive effects of KM, several antagonists were used. Also, a rotarod test was carried out for assessing motor performance. Findings/Results: The intracerebroventricular and/or intrathecal microinjections of KM (40 μg/rat) had partially antinociceptive effects in the tail-flick test in rats (P < 0.05). In the formalin paw model, the intrathecal microinjection of KM had antinociceptive effects in phase 1 (20 and 40 μg/rat; P < 0.05 and P < 0.01, respectively) and phase 2 (20 and 40 μg/rat; P < 0.01 and P < 0.001, respectively). Using naloxonazine and/or bicuculline approved the involvement of opioid and GABA receptors in the central antinociceptive effects of KM, respectively. Moreover, KM reduced the expression levels of caspase 6, interleukin-1β, tumor necrosis factor-α, and interleukin-6. The antinociceptive effects of KM were not linked to variations in the locomotor activity. Conclusion and implications: It can be concluded that KM has remarkable antinociceptive effects at a spinal level, which is associated with the presence of the inflammatory state. These impacts were undetectable following injections in the lateral ventricle. The possible mechanisms of KM antinociception are possibly linked to various modulatory pathways, including opioid and GABA receptors.

High-fat diets (HFDs) adversely influence glutamate metabolism and neurotransmission. The precise role of the group II metabotropic glutamate receptors (mGluR2/3) antagonist on spatial memory deficit following consumption of HFD has not yet been clarified. Therefore, in this study, we examined the effects of post-training administration of mGluR2/3 antagonism; LY341495 on spatial memory in rats fed with HFD (for 10 weeks) by using Morris Water Maze (MWM) task. The training session for testing memory acquisition in MWM consisted of 4 trials per day for 4 consecutive days. Twenty-four hours after the last training session the spatial probe test (retention) was given. Intraperitoneal injection (i.p) injection of LY341495 was done 30 min before probe test. Our results showed that 10 weeks consumption of HFD had no significant effect on escape latency and swimming distance in memory acquisition. Our finding showed that consumption of a HFD leads to reference memory impairment in the probe test. HFD animals spent less time in the target zone in compare with control animals. Also, LY341495 improved HFD-induced reference memory (retention) impairment. HFD animals treated with LY341495 spent more time in the target zone in compare with HFD animals. Escape latencies to find the visible platform during visual task were same in all experimental groups, indicating no visual impairment in the animals. We propose that a HFD may act through mGluR2/3 within the brain to reduce synaptic plasticity, which impairs memory retrieval, and post-training administration of LY341495 can reduce HFD-induced reference memory impairment.

IntroductionAlzheimer’s disease (AD) is a neurodegenerative disease that is characterized by amyloid plaque deposits, neuronal cell loss, and memory impairment. Granulocyte-colony stimulating factor (G-CSF) is a growth factor associated with AD improvement. Stromal cell-derived factor-1 (SDF-1) mediates therapeutic effects of G-CSF. This study investigated the effect of combination treatment of G-CSF and SDF-1 on amyloid plaque deposits, apoptosis, and behavior of AD rats.MethodsIntracerebroventricular amyloid-beta [Aβ(1-42)] peptide was used to induce AD in Aβ rats. There were six groups including naive control, sham-operated, Aβ, Aβ + G-CSF, Aβ + SDF-1, and Aβ + G-CSF + SDF-1. SDF-1 intra-cerebroventricular (ICV), G-CSF Subcutaneous (SC), or a combination of them were administered to Aβ rats weekly for 2 months. The cognition and memory were assessed using the novel object recognition, passive avoidance, and Morris water maze tests. Next, rat brains were removed and the amyloid plaque and apoptosis were detected in the brain and hippocampus using immunohistochemistry and TUNEL assay, respectively.ResultsThe amyloid-beta and apoptotic cell levels dropped in groups receiving SDF-1 and G-CSF combination compared to the Aβ group. Also, number of microglial cells increased significantly in the combination group compared to other treatment groups. Moreover, learning and memory were significantly improved in the combination group compared to the Aβ groups (P < 0.05).ConclusionSDF-1 and G-CSF combination therapy can offer a promising strategy for AD.

Introduction: The effectiveness of antioxidants on learning and memory improvement has been shown, previously. Due to the high level of antioxidants, available in Origanum vulgare, the present experiment aimed to examine the effect of aqueous extract of O. vulgare on passive avoidance learning (PAL) in male Wistar rats. Methods: This study was performed on 30 male Wistar rats weighing 250 to 290 g. The rats were randomly assigned into five groups (n=6), as follows: the control, sham (saline), and three groups treated with different doses of O. vulgare extract (150, 250, and 350 mg/kg). The saline or extract was administered via daily oral gavage for 14 days. The groups were then subjected to the passive avoidance task, and their behaviors were recorded. The rats’ locomotor activity was also measured using the open field test. Results: The number of trials to acquisition was significantly lower in the "O. vulgare (350 mg/ kg)" group than the control group. The step-through latency and the time spent in the dark compartment in the retention test, was significantly higher and lower in the "O. vulgare (250 and 350 mg/kg)" groups than the control group, respectively. No significant differences were found in the distances traveled among the experimental groups in the open field test. Conclusion: Aqueous extract of O. vulgare can enhance learning and memory. The high levels of antioxidants in O. vulgare extract may be responsible for its effectiveness in learning and memory.

ABSTRACT Induction of long-term potentiation (LTP) increases the storage capacity of synapses in the hippocampal dentate gyrus (DG). Irisin is a myokine generated from FNDC5 (a gene precursor) during exercise. Although intra-cornu ammonis 1 administration of irisin fortifies LTP in mice with Alzheimer's disease, the effects of intra-DG injection of irisin on the LTP in rats remains to be elucidated in vivo. In this study, male Wistar rats were randomly divided into a control group (saline), irisin (0.5, 1, and 1.5 μg/rat), and dimethyl sulfoxide (DMSO). After treatment, the population spike (PS) amplitude and slope of excitatory postsynaptic potentials (EPSP) were measured in the DG of rats in vivo. Moreover, following completion of the experiments, the stimulating and recording sites in the hippocampus were confirmed histologically from brain sections. Furthermore, biochemical assays like malondialdehyde (MDA), total antioxidant capacity (TAC), and total oxidant status (TOS) were evaluated (the antioxidant markers were analyzed in the plasma). Our results suggest that all doses of irisin (0.5, 1, 1.5 μg/rat) caused an increase in the EPSP slope and PS amplitude when compared with the control group. In addition, the results obtained showed that irisin decreased TOS and MDA levels while increasing TAC levels as a marker of lipid peroxidation in plasma. The present report provides direct evidence that irisin affects the activity-dependent synaptic plasticity in the dentate gyrus.

Abstract Background Proteins encoded by Suppressors of cytokine signaling (SOCS) genes have critical roles in the regulation of immune responses. Meanwhile, several lines of evidence support the presence of immune dysfunction in bipolar disorder (BD) patients. Methods In the present study, we assessed expression levels of SOCS1–3 and SOCS5 genes in peripheral blood of patients with BD and healthy subjects. Results All SOCS genes were up-regulated in patients compared with healthy subjects. However, when comparing patients with sex-matched controls, the significant differences were observed only in the male subjects except for SOCS5 which was up-regulated in both male and female patients compared with the corresponding control subjects. Significant pairwise correlations were found between expression levels of genes in both patients and controls. Based on the area under curve values, SOCS5 had the best performance in the differentiation of disease status in study participants (AUC = 0.92). Combination of four genes increased the specificity of tests and resulted in diagnostic power of 0.93. Conclusion Taken together, these data suggest a role for SOCS genes in the pathogenesis of BD especially in the male subjects. Moreover, peripheral expression levels of SOCS genes might be used as a subsection of a panel of diagnostic biomarkers in BD.

Little is known about the effects of methamphetamine (Meth) and buprenorphine (Bup) on memory and learning in rats. The aim of this investigation was to examine the impact of Meth and Bup on memory and learning. Fourteen male Wistar rats weighing 250–300 g were assigned to four groups: Sham, Meth, Bup, and Meth + Bup and were treated for 1 week. Spatial learning and memory, avoidance learning, and locomotion were assessed using the Morris water maze, passive avoidance learning, and open field tests, respectively. Meth and Bup impaired spatial learning and memory in rats. Co-administration of Meth + Bup did not increase the time spent in the target quadrant compared to Meth alone in the MWM. The Bup and Meh + Bup groups were found with an increase in step-through latency (STLr) and a decrease in the time spent in the dark compartment (TDC). Meth and Bup had no effects on locomotor activity in the open field test. Bup showed a beneficial effect on aversive memory. Since Bup demonstrates fewer side effects than other opioid drugs, it may be preferable for the treatment of avoidance memory deficits in patients with Meth addiction.

Introduction: Methamphetamine (Meth) and Buprenorphine (BUP) modulate pain perception. However, the antinociceptive effects of their interactions, which affect through different systems, are unclear in rats. This study aimed to compare the analgesic effects of Meth, BUP, and their coadministration, as well as the effect of withdrawal from these substances on nociception in male rats. Methods: In this experiment, 40 male Wistar rats (weight: 250-300 g) were categorized into four groups: control, Meth, BUP, or BUP+Meth. After seven days of treatments, the antinociceptive effects were assessed using the hot plate and the tail flick tests. The differences among the groups were analyzed with ANOVA and Tukey’s post hoc tests. P values less than 0.05 were considered significant. Results: Meth and BUP increased the reaction times during the hot plate and tail flick tests. The combination of Meth and BUP increased reaction time more than Meth or BUP alone. Conclusion: The significantly high reaction times in rats treated with Meth and BUP indicate that these substances have antinociceptive effects. In addition, Meth enhanced the antinociceptive effects of BUP. These synergistic effects might occur through the dopaminergic, serotonergic, and or adrenergic systems.

Introduction: Melissa officinalis (MO) or lemon balm is traditionally used as a sedative and anti-spasm herbal medicine. There is also evidence that this plant has effects on learning and memory. This study examined the effect of a hydro-alcoholic extract of MO on passive avoidance learning (PAL) and memory in male rats. Methods: A total of 40 adult male Wistar rats were randomly distributed into four groups (200 to 220 g; n = 10 per group); three dose groups (50, 100, and 200 mg/kg of the hydro-alcoholic extract of MO) and vehicle control (saline) group. Saline or doses of extract were administered daily for 14 days by oral gavage. The rats were trained to enter the shuttle box to record their behavior in the PAL task. A retrieval test was performed 24 hours following training. Results: A significant difference was seen in performance among MO groups and the control. MO administered animals had a decreased number of acquisition trials (P < 0.05). In the retention task, MO administered animals had an increased step-through latency (SLT) (P < 0.01), and a decreased latency in the dark compartment (P < 0.001) compared to the control group. Conclusion: The results of the study show that MO can improve learning and memory in the PAL task. Further investigation is needed to enhance our understanding of the neurobiological mechanisms of the MO extract and its effects on learning and memory.

BackgroundMolybdenum cofactor sulfurase (MOCOS) is an enzyme participating in purine metabolism. The aim of current study was to evaluate the role of a single nucleotide polymorphism (SNP) in the coding gene (rs594445) in mood disorders and methamphetamine addiction.MethodsThis SNP was genotyped in 200 persons with methamphetamine addiction, 85 patients with bipolar disorder 1 (BP1), 78 patients with BP2, 33 patients with major depressive disorder (MDD) and 200 age-/sex-matched normal subjects using the tetra-primer amplification-refractory mutation system (ARMS)-PCR technique.ResultsThe rs594445 was associated with methamphetamine addiction in co-dominant model [A/A vs C/C: OR (95% CI) = 0.466 (0.252–0.864), P-value = 0.014; C/A vs C/C: OR (95% CI) = 0.641 (0.418–0.981), P-value = 0.04]. This SNP was also associated with this trait in dominant model [OR (95% CI) = 0.591 (0.398–0.879), P-value = 0.009]. The A allele of rs594445 had a protective role against methamphetamine addiction [A vs C: OR (95% CI) = 0.645 (0.48–0.866), P-value = 0.004]. The rs594445 was associated with BP1 in co-dominant model [C/A vs C/C: OR (95% CI) = 0.423 (0.230–0.778), P-value = 0.005]. However, the associations were insignificant in other inheritance models.ConclusionFinally, there were no significant associations between the mentioned SNP and risk of BP2 or MDD in any inheritance model. The present project highlights the role rs594445 in two psychiatric conditions and implies the presence of common genetic factors for these disorders.

The susceptibility to cardiovascular disease in offspring could be reduced prior to birth through maternal intervention, before and during pregnancy. We evaluated whether the initiation periods of maternal exercise in preconception and pregnancy periods induce beneficial effects in the adult male offspring. Thirty-two female rats were divided into control and exercise groups. The exercise groups involve exercise before pregnancy or the preconception periods, exercise during pregnancy, and exercise before and during pregnancy. The mothers in the exercise groups were run on the treadmill in different periods. Then the birth weight and weekly weight gain of male offspring were measured, and the blood and left ventricle tissue of samples were collected for analysis of the Sirtuin 6 (Sirt6) and insulin growth factor-2 (IGF-2) gene expression, serum levels of low-density lipoprotein (LDL), high-density lipoprotein (HDL), cholesterol (Cho), and triglycerides (TG). There was no significant difference in the birth weight of offspring groups (P = 0.246) while maternal HIIT only during pregnancy leads to reduce weekly weight gain of offspring. Our data showed that Sirt6 and IGF-2 gene expression was increased (P = 0.017) and decreased (P = 0.047) by maternal exercise prior to and during pregnancy, respectively. Also, the serum level of LDL (p = 0.002) and Cho (P = 0.007) were significantly decreased and maternal exercise leads to improves the running speed of the adult male offspring (p = 0.0176). This study suggests that maternal HIIT prior to and during pregnancy have positive intergenerational consequence in the health and physical readiness of offspring.

Purpose: Ischemia-Reperfusion (IR) injury is one of the most common cardiac disorders leading to irreversible heart damage. Many underlying mechanisms seem to be involved, among which disruption of cellular autophagy balance. Since physical training has a beneficial effect on the improvement of autophagy balance, it may have a cardioprotective effect against IR injury. This study investigates the protective role of aerobic training from cardiac IR injury and the autophagy process as a possible mechanism. Methods: Thirty-two male Wistar rats (8 weeks old) were divided into control, sham, control plus IR, and training plus IR groups (8 rats each). The training group was exercised aerobically on a treadmill for 8 weeks (5 d/wk). After 8 weeks, the anesthetized rats underwent left thoracotomy (sham, control plus IR, and training plus IR groups) to access the left anterior descending coronary artery, which was occluded by a silk suture for 30 min and then released for 90 min of reperfusion (IR groups). Triphenyltetrazolium chloride staining was used to determine the infarct size. The gene expression of Beclin-1 was evaluated by real-time polymerase chain reaction. One-way ANOVA was used for statistical analysis with the significance level set at P≤0.05. Results: The cardiac infarct size was smaller in training plus IR (20.24±5.7%) group compared to that in the control plus IR (35.9±2.3%) group (P≤0.05). On the other hand, IR operation significantly increased the gene expression of Beclin-1, while exercise training prevented expression of the mentioned gene in training plus IR group (P≤0.05). Conclusion: Aerobic training can protect the heart against Ischemia-Reperfusion injury. It seems that improvement of autophagy balance during IR injury may be involved in exercise-induced cardioprotection against Ischemia-Reperfusion.

Introduction: Methamphetamine (METH) is a neurotoxic psychostimulant with highly addictive potential that leads to compulsive drug use and vulnerability to relapse. Environmental cues, such as drug exposure, peer influence, and social stress, are the powerful triggers of drug relapse. In this study,.we.tried.to.find.out.the effect of acute and chronic restraint stress on reinstatement of extinguished METH-induced Conditioned Place.Preference.(CPP).in.rats. Methods: Subcutaneous (SC) administration of METH (0.125, 0.25, 0.5, 1, 2 and 4 mg/kg) could induce CPP and it was found that.METH with the dose of 0.5 mg/kg was more potent than other doses. In.extinction phase,.rats.were.put.in.the.CPP.box.for.30.min.per.day.for.8 consecutive days..After.extinction,.animals.were.exposed.to restraint stress (3-h period, as an acute stress) 60.min.before.subcutaneous.administration.of.ineffective.dose.of.METH.(0.125.mg/kg).in.order.to.reinstate.the.extinguished.METH-induced CPP. For induction of the chronic stress during extinction phase, the animals were exposed to the restraint stress for one hour per day. Results: The results showed that the effective dose of METH to induce CPP was 0.5 mg/kg..Based on the results, physical.stress.(restraint stress) whether acute and chronic, can.significantly.induce.reinstatement.of METH-induced CPP (P˂0.001) in extinguished animals. Conclusion: Additionally, the chronic restraint stress could reduce duration of extinction (maintenance) of METH-induced CPP. It seems that exposure to the stress induces the relapse in abstinent amphetamine, but acute and chronic situation have a different reaction.

Introduction: Previous studies have shown that the cannabinoid system is involved in anxiety.In addition, transient receptor potential vanilloid type-1 (TRPV1) channels are new targets for the development of anxiolytics. The present study investigated the possible interaction between the cannabinoid and vanilloid systems on anxiety-like behavior in rats. Methods: Four different groups of male Wistar rats received intraperitoneal (IP) injections of (1) vehicle (DMSO+saline), (2) cannabinoid receptor agonist WIN55212-2 (WIN)(1 mg/kg), (3) TRPV1 receptor antagonist capsazepine (CPZ) (5 mg/kg), or (4) combined WIN (1 mg/kg) and CPZ (5 mg/kg) treatment 30 min before testing in the elevated plus maze. Results: The results showed that compared to the control (vehicle), both WIN and CPZ increased the time spent and number of entries on the open arms. Co-administration of WIN and CPZ had a synergistic effect, i.e., the number of entries and time spent on the open arms was greater than that in the groups administered the two compounds alone. The total distance travelled by rats and total number of entries on to the arms did not significantly difer between groups. Conclusion: Acute neuropharmacological blockade of the TRPV1 receptor or stimulation of the CB1 receptor produced an anxiolytic effect. It seems that antagonism of the vanilloid system modulates cannabinoid outputs that increase the anxiolytic effect. TRPV1 antagonism may alter endocannabinoids production, which in turn enhances anxiolytic effect. These results suggest interaction of two systems or sharing some signaling pathways that affect anxiety expression.

Context: High-fat diet (HFD) can cause deficits in learning and memory through oxidative stress and increase Alzheimer disease risk. Rosa damascena Mill. (Rosaceae) extract possesses potent antioxidant properties. Objective: This study investigated the effects of the hydroalcoholic extracts of petals of R. damascena on learning and memory in male rats consuming an HFD. Materials and methods: Forty male Wistar rats (200–250 g) were randomly assigned to four groups: control, R. damascena extract, HFD and HFD + extract. The extract (1 g/kg bw daily) was administered by oral gavage for 1 month. Animals were allowed free access to high-fat chow for 3 months. The Morris water maze and the passive avoidance learning tests were used to assess learning and memory. Results: In the passive avoidance learning test, the step-through latencies in the retention test (STLr) of the extract (147.4 ± 23.3) and HFD (150.3 ± 25.2) groups were significantly lower than those of the control group (270.4 ± 10.5) (respectively, p

There is some evidence in traditional medicine for the effectiveness of Thymus vulgaris (百里香 bǎi lǐ xiāng) in the treatment of anxiety in humans. The elevated plus-maze (EPM) has broadly been used to investigate anxiolytic and anxiogenic compounds. The present study investigated the effects of extract of T. vulgaris on rat behavior in the EPM. In the present study, the data were obtained from male Wistar rats. Animals were divided into four groups: saline group and T. vulgaris groups (50 mg/kg, 100 mg/kg, and 200 mg/kg infusion for 7 days by feeding). During the test period, the total distance covered by animals, the number of open- and closed-arm entries, and the time spent in open and closed arms of the EPM were recorded. T. vulgaris increased open-arm exploration and open-arm entry in the EPM, whereas extract of this plant has no effects on the total distance covered by animals and the number of closed-arm entries. The results of the present experiment indicate that T. vulgaris may have an anxiolytic profile in rat behavior in the EPM test, which is not influenced by the locomotor activity. Further research is required to determine the mechanisms by which T. vulgaris extract exerts an anxiolytic effect in rats.

Objective(s): Nucleus Raphe Magnus (NRM) that is involved in the regulation of body temperature contains nitric oxide (NO) synthase. Considering the effect of NO on skin blood flow control, in this study, we assessed its thermoregulatory role within the raphe magnus. Materials and Methods: To this end, tail blood flow of male Wistar rats was measured by laser doppler following the induction of hypothermia. Results: Intra-NRM injection of SNP (exogenous NO donor, 0.1- 0.2 μl, 0.2 nM) increased the blood flow. Similarly, unilateral microinjection of glutamate (0.1- 0.2 μl, 2.3 nM) into the nucleus increased the blood flow. This effectof L-glutamate was reduced by prior intra NRM administrationof NO synthase inhibitor NG-methyl-L-arginine or NG-nitro-L-argininemethyl ester (L-NAME, 0.1 µl, 100 nM). Conclusion: It is concluded that NO modulates the thermoregulatory response of NRM to hypothermia and may interactwith excitatory amino acids in central skin blood flow regulation.

Introduction: Previous studies have shown that cannabinoidergic system is involved in anxiety. However, there are controversial reports in the experimental studies. The aim of this study is to evaluate the effect of pharmacological stimulation or blocking of CB1 receptors and inhibition of endocannabinoid degradation in anxiety like behavior in elevated plus-maze (EPM) test in rat. The EPM is one of the most widely used animal models of anxiety. Methods: Male Wistar rats were randomly allocated to ten groups. Different groups of animals intraperitoneally received Win-55212 (0.3, 1 and 5 mg/kg) as CB1 receptor agonist, AM- 251 (0.3, 1 and 5 mg/kg) as CB1 receptor antagonist, URB-597 (0.03, 0.1 and 0.3 mg/kg) as endocannabinoid breakdown inhibitor or saline (as control group) 30 min before submitting into EPM test. Results: The results showed that compared to the control group, Win-55212 (1 and 5 mg/kg) and URB-597 (0.1 and 0.3 mg/kg) significantly increased both of the time and percentage of entries into open arms. AM-251 (1 and 5 mg/kg) significantly decreased the time and percentage of entries into open arms in the EPM test. These substances have no effects on the total distance covered by animals and number of closed arm entries. Discussion: It is concluded that activation of cannabinoid receptor exert anxiolytic effect while blocking of cannabinoid receptor resulted in anxiety behavior. The locomotor activity was not significantly changed by cannabinoid system. It is suggested that potentiation of cannabinoid system may be therapeutic strategy for the anxiety behavior.