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Maternal bacterial and viral infections that induce neuroinflammation in the developing brain are associated with impaired cognitive function and increased anxiety in the offspring. In contrast, maternal infection with the immunoregulatory murine gastrointestinal (GI) nematode, Heligmosomoides bakeri, appears to benefit neurodevelopment as juvenile 2- and 3-week-old male and female offspring had enhanced spatial memory, which may be due to a Th2/Treg biased neuroimmune environment. Here, the impact of maternal H. bakeri infection during pregnancy and lactation on the spatial and anxiety-like behaviours of adult, 3-month-old uninfected male and female offspring was explored for the first time. It was observed that adult female offspring of H. bakeri-infected dams had enhanced spatial reference memory and reduced anxiety-like behaviour compared to females of uninfected dams. These effects were not observed in adult male offspring. Thus, the positive influence of a maternal GI nematode infection on spatial memory of juvenile offspring persists in adult female offspring.

Maternal bacterial and viral infections that induce neuroinflammation in the developing brain are associated with impaired cognitive function and increased anxiety in the offspring. In contrast, maternal infection with the immunoregulatory murine gastrointestinal (GI) nematode, Heligmosomoides bakeri , appears to benefit neurodevelopment as juvenile 2- and 3-week-old male and female offspring had enhanced spatial memory, which may be due to a Th2/Treg biased neuroimmune environment. Here, the impact of maternal H. bakeri infection during pregnancy and lactation on the spatial and anxiety-like behaviours of adult, 3-month-old uninfected male and female offspring was explored for the first time. It was observed that adult female offspring of H. bakeri -infected dams had enhanced spatial reference memory and reduced anxiety-like behaviour compared to females of uninfected dams. These effects were not observed in adult male offspring. Thus, the positive influence of a maternal GI nematode infection on spatial memory of juvenile offspring persists in adult female offspring. [ABSTRACT FROM AUTHOR]

Aging is a normal physiological process influenced by the combination of multiple mechanisms, primarily oxidative stress and neuroinflammation, which impact general physiology and brain function. Phenolic compounds have demonstrated the ability to slow down the aging process of the brain due to their antioxidant and anti-inflammatory effects. This study assessed the protective properties of catechin and polyphenon-60 in non-pathologically aged rats regarding visuo-spatial learning and the oxidative status of the frontal cortex. Old animals were treated with catechin or green tea extract (polyphenon-60) for 36 days, daily. Healthy old and young rats were used as controls. During the first training phase, treated rats executed the test better, locating the target in less time compared with the controls. Biomarkers of oxidative stress (catalase activities, superoxide dismutase, glutathione reductase, and glutathione S-transferase) were reduced in the brain of old animals, although their activities were partially improved after both antioxidant treatments. Furthermore, the rise in the production of reactive oxygen species and malondialdehyde levels—a marker of lipid peroxidation—in the frontal cortex of aged animals was significantly ameliorated after the interventions. In conclusion, old rats exhibited enhanced cognitive function and reduced stress levels following the administration of catechin and polyphenon-60. [ABSTRACT FROM AUTHOR]

Abstract Background All mouse strains are different, before choosing a strain for a large study, a small scale study should be done. In this study, we compared young males of two mouse strains, C57BL/6J and the hybrid B6129SF1/J, and gained knowledge on their performance in three different behavioral tests; open field (OF) test, Barnes maze (BM) test and a restraint stress test. Results We found that the young males of the C57BL/6J strain spent more time moving in the OF. In the BM, the hybrid covered less ground before reaching the goal box during the first three sessions, than the C57BL/6J. The hybrid left more fecal pellets than C57BL/6J both in OF and BM. During the stress test, the C57BL/6J had a lower corticosterone response than the hybrid. Conclusions Our findings indicate that the C57BL/6J has a presumably higher locomotor activity and/or explorative behavior than the hybrid, while the hybrid appeared more sensitive to stress.

Rationale: Alzheimer's disease (AD) is a chronic neurodegenerative disorder characterized by cognitive decline and synaptic failure. Objective: The present study was designed to explore the possible protective effects of policosanol (PCO) on spatial cognitive capacity, long-term potentiation (LTP) induction, oxidant/antioxidant status, and Aβ plaques formation in an AD rat model induced by intracerebroventricular (ICV) injection of Aβ1–40. Methods: Healthy adult male Wistar rats were randomly divided into control, sham (ICV injection of 5 µl phosphate-buffered saline), AG (50 mg/kg; P.O., as PCO vehicle), PCO (50 mg/kg; P.O.), AD model (ICV injection of 5 µl Aβ), AD + AG (50 mg/kg; P.O.), and AD + PCO (50 mg/kg; P.O.). Treatments were performed for eight consecutive weeks. At the end of the treatment course, spatial learning and memory functions, hippocampal long-term potentiation (LTP) induction, malondialdehyde (MDA), and total thiol group (TTG) levels, as well as the formation of Aβ plaques, were examined. Results: The results showed that injection of Aβ reduced spatial learning and memory abilities in the Barnes maze test, which was accompanied by decreases in field excitatory postsynaptic potential (fEPSP) slope, population spike (PS) amplitude, and TTG level and increases in Aβ plaque accumulation and MDA content. In contrast, PCO treatment improved all the above-mentioned changes in the Aβ-infused rats. Conclusions: The results suggest that amelioration of hippocampal synaptic plasticity impairment, modulation of oxidant/antioxidant status, and inhibition of Aβ plaque formation by PCO may be the mechanisms behind its protective effect against AD-associated spatial cognitive decline. [ABSTRACT FROM AUTHOR]

BackgroundCognition and brain function is critical through childhood and should be improved with balanced diets. Incorporating bioactive ingredients such as omega-3 polyunsaturated fatty acids (ω3 PUFAs) and probiotics into food formulations could be used as an approach to improve cognitive function. This study evaluated the effects on cognitive capacity of complementing rodent diets with chocolate, by itself and in combination with ω3 PUFAs from fish oil and probiotics.MethodsSpatial learning and memory in the rats were determined by the Barnes maze test in short- and long-term memory. Samples from the cecum were obtained to assess microbial counts (Lactobacillus, Bifidobacterium, Enterobacteriaceae, and total bacteria), and brains were recovered to analyze the neural morphology of the tissues. Also, glucose, brain weights, and epididymal tissue were analyzed.ResultsThe combination of chocolate with fish oil and probiotics improved the memory of rats compared to the result of each bioactive compound when evaluated separately. Treatments did not affect sugar level, epididymal adipose tissue, or brain weight. On the other hand, consuming probiotics alone or in combination with chocolate decreased Enterobacteria counts, while Lactobacillus and Bifidobacteria counts were not affected. Neural morphological analysis showed that combining chocolate with probiotics and ω3 PUFAs increased the number of neurons in the hippocampal CA1 and CA3 regions.ConclusionChocolate added with probiotics and ω3 PUFAs improved spatial memory and learning in the studied model.

Background: All mouse strains are different, before choosing a strain for a large study, a small scale study should be done. In this study, we compared young males of two mouse strains, C57BL/6J and the hybrid B6129SF1/J, and gained knowledge on their performance in three different behavioral tests; open field (OF) test, Barnes maze (BM) test and a restraint stress test. Results: We found that the young males of the C57BL/6J strain spent more time moving in the OF. In the BM, the hybrid covered less ground before reaching the goal box during the first three sessions, than the C57BL/6J. The hybrid left more fecal pellets than C57BL/6J both in OF and BM. During the stress test, the C57BL/6J had a lower corticosterone response than the hybrid. Conclusions: Our findings indicate that the C57BL/6J has a presumably higher locomotor activity and/or explorative behavior than the hybrid, while the hybrid appeared more sensitive to stress. [ABSTRACT FROM AUTHOR]

Numerous studies have supported benefits of omega-3 supplementation using Menhaden fish oil (FO) to promote brain maturation and plasticity during critical developmental periods. The goal of this study was to determine sex-specific immediate and delayed impact of adolescent omega-3 supplementation on visuospatial memory and cognitive flexibility. Sixty-four Wistar rats (n = 32 males and females) received daily FO or soybean oil (CSO) supplementation via oral gavage (0.3 mL/100 g body weight) from postnatal day 28–47. The Barnes Maze Test (BMT) was used to measure visuospatial memory and reversal learning trials (RL) determined cognitive flexibility. Juveniles underwent testing immediately after the gavage period, while adults began testing on postnatal day 90. Adult rats showed reduced working memory errors (WME) and gradual decrease in escape latencies compared to juveniles. Importantly, adult FO-supplemented females displayed fewer WME than males, while males' performance benefited from CSO supplementation. Overall, sex- and supplementation-dependent effects supported a positive impact of FO in female rats only. Our findings support the potential for supplementation limited to the early adolescence period to influence adulthood spatial learning and cognitive flexibility in a sex-specific manner. [ABSTRACT FROM AUTHOR]

Introduction: Synaptic plasticity has been suggested as the primary physiological mechanism underlying memory formation. Many experimental approaches have been used to investigate whether the mechanisms underlying Long-Term Potentiation (LTP) are activated during learning. Nevertheless, little evidence states that hippocampal-dependent learning triggers synaptic plasticity. In this study, we investigated if learning and memory in the Barnes maze test are accompanied by the occurrence of LTP in Schaffer collateral to CA1 synapses in freely moving rats. Methods: The rats were implanted with a recording electrode in stratum radiatum and stimulating electrodes in Schaffer collaterals of the CA1 region in the dorsal hippocampus of the right hemisphere. Following the recovery period of at least 10 days, field potentials were recorded in freely moving animals before and after training them in Barnes maze as a hippocampal-dependent spatial learning and memory test. The slope of extracellular field Excitatory Postsynaptic Potentials (fEPSPs) was measured before and after the Barnes maze test. Results: The results showed that the fEPSP slope did not change after learning and memory in the Barnes maze test, and this spatial learning did not result in a change in synaptic potentiation in the CA1 region of the hippocampus. Conclusion: Spatial learning and memory in the Barnes maze test are not accompanied by LTP induction in Schaffer collateral-CA1 synapses.

This paper is focused on the dynamics of the formation of conditioned responses in rats that experienced 14-day moderate magnetic shielding and were placed into a shelter setup when conducting the Barnes maze task. It was found that the acquisition rate of the conditioned active avoidance response was faster in rats under magnetic shielding conditions than that in the control animals. A direct accelerating effect of a moderate geomagnetic environment on the acquisition of the conditioned active avoidance response is thought to be extremely unlikely and the observed effect appears to be due to well-known biorhythm changes in pain sensitivity in hypomagnetic conditions associated with the development of hyperalgesia during the first week, which is an additional motivation for the formation of the conditioned active avoidance response in the Shelter setup. A two-phase change in pain sensitivity of male rats for a 14-day period was shown in the electrostimulation setup: hyperalgesia occurred during the first week and hypoalgesia was induced during the second week. The Barnes maze task did not reveal any differences between groups of control animals and experimental animals in recorded behavioral indices in hypomagnetic conditions within a 14-day period. Therefore, the accelerated formation of conditioned active avoidance response in rats under hypomagnetic conditions is most likely due to a significant increase in pain sensitivity during the first week of the experiment. [ABSTRACT FROM AUTHOR]

• Ursolic acid restores motor dysfunction induced due to rotenone administration. • Ursolic acid attenuate the cognitive dysfunction as observed in Barnes maze test. • Ursolic acid protect TH positive neuronal degeneration within SNpc and striatum. • Ursolic acid treatment alleviates oxidative stress and inflammation. • Ursolic acid promotes mitobiogenesis aiding to its neuroprotective effect. Parkinson's disease (PD) is an age associated, progressive and a second most common neurodegenerative disease. It is caused due to degeneration of dopaminergic neurons in substantia nigra (SN). Various studies implicate mitochondrial dysfunction, oxidative stress, altered degradation of misfolded proteins in PD pathogenesis. Ursolic acid (UA), a natural pentacyclic triterpenoid carboxylic acid, is reported to possess a number of biological activities viz. anti-oxidant, anti-inflammatory etc. The focus of our study was to assess the neuroprotective potential of UA against the rotenone induced pathophysiological alterations. In this study rats were subjected to stereotaxic bilateral injection of rotenone (12 μg/μl) in SN. Further, they were treated per-orally with UA (5 and 10 mg/kg) for 30 days. During the study, neurobehavioral tests comprising Rota-rod, Open field and Barnes maze (BMT) were conducted. At the end of 30 days, the antioxidant (Reduced glutathione, superoxide dismutase, catalase and lipid peroxidation), inflammatory (TNF-α) parameters, mitochondrial complex I, mitochondrial biogenesis (MB) and immunohistochemical analysis (TH positive neurons, Glial Fibrillary Acidic Protein (GFAP)) was performed. The results exhibited significant amelioration in the motor deficits by UA which can be attributed to the protection of TH positive neurons from degeneration. A significant improvement in the cognitive function due to UA was observed in BMT. Biochemically, the oxidative stress and inflammation triggered by rotenone was significantly diminished by UA. It also significantly obviated the complex I inhibition and promoted MB. The preliminary results thus firmly advocate the neuroprotective potential of UA to prevent rotenone induced neurotoxicity in rats. [ABSTRACT FROM AUTHOR]

We investigated the effect of long-term administration of kale (Brassica oleracea L. var. acephala) on hippocampal gene expression in senescence-accelerated mouse prone 8, SAMP8. The mice were fed the AIN-93M diet containing 0.05% (w/w) kale extract (KE) for 31 weeks. The long-term KE administration resulted in significant decreases in escape latency compared to control group in the Barnes maze test. According to the DNA microarray analysis, KE administration significantly up-regulated various genes of G protein-coupled receptors pathways in the hippocampus. In contrast, KE administration significantly down-regulated genes of complement and coagulation cascades and focal adhesion-PI3K-Akt-mTOR-signaling pathway. Up-regulated pathways included genes involved in the modulation of neurotransmission and synaptic plasticity. Down-regulated pathways included genes related to the thrombus formation. These results could provide partial information about one of the molecular mechanisms underlying the suppressive effect of KE intake against cognitive decline. [ABSTRACT FROM AUTHOR]

The Barnes maze is a task used to assess spatial learning and memory in rodents. It requires animals to learn the position of a hole that can be used as an escape from a bright and open arena. The often-used parameters of latency and path length to measure learning and memory do not reflect the different navigation strategies chosen by the animals. Here, we propose an 11-point scoring scheme to classify the search strategies developed by the animals during the initial training as well as after the change of the escape target to a new position. Strategy scores add an important dimension to time and path length to assess the behavior in this popular maze. [ABSTRACT FROM AUTHOR]

Introduction: Synaptic plasticity has been suggested as the primary physiological mechanism underlying memory formation. Many experimental approaches have been used to investigate whether the mechanisms underlying Long-Term Potentiation (LTP) are activated during learning. Nevertheless, little evidence states that hippocampal-dependent learning triggers synaptic plasticity. In this study, we investigated if learning and memory in the Barnes maze test are accompanied by the occurrence of LTP in Schaffer collateral to CA1 synapses in freely moving rats. Methods: The rats were implanted with a recording electrode in stratum radiatum and stimulating electrodes in Schaffer collaterals of the CA1 region in the dorsal hippocampus of the right hemisphere. Following the recovery period of at least 10 days, field potentials were recorded in freely moving animals before and after training them in Barnes maze as a hippocampal-dependent spatial learning and memory test. The slope of extracellular field Excitatory Postsynaptic Potentials (fEPSPs) was measured before and after the Barnes maze test. Results: The results showed that the fEPSP slope did not change after learning and memory in the Barnes maze test, and this spatial learning did not result in a change in synaptic potentiation in the CA1 region of the hippocampus. Conclusion: Spatial learning and memory in the Barnes maze test are not accompanied by LTP induction in Schaffer collateral-CA1 synapses. [ABSTRACT FROM AUTHOR]

Temporal lobe epilepsy (TLE) is one of the most frequent forms of focal epilepsy; patients with this condition, in addition to exhibiting complex seizures, also exhibit cognitive deficits. In the temporal lobe, the hippocampus, a structure relevant to learning and memory processes, is particularly affected by epilepsy. In animal models of TLE induced by pilocarpine, learning and memory deficiencies associated with changes in synaptic plasticity of the hippocampus have been reported. Cerebrolysin (CBL) is a biologically active mixture of low molecular weight peptides with neuroprotective and neurotrophic effects. The objective of the present study was to determine whether subchronic CBL treatment of rats in the chronic phase of TLE reduces the number and intensity of seizures, and whether CBL treatment can improve cognitive deficits (learning and spatial memory) and dendritic morphology in granular dentate neurons of the hippocampus. Temporal lobe epilepsy (lithium–pilocarpine model) was induced in male Wistar rats (weight, 250–300 g). Two epileptic groups were studied, in which CBL (538 mg/kg) or vehicle was administered intraperitoneally for 5 consecutive days per week for 3 weeks. Respective controls were also included in the study. At the end of treatment, the Barnes maze test (BMT) was used to assess spatial navigational learning and memory. The dendritic morphology of the dentate gyrus was also evaluated using the Golgi–Cox staining method. Results of this study did not support an antiepileptic effect of CBL. Epileptic animals treated with this agent exhibited secondarily generalized seizures similar in frequency and intensity to those of epileptic animals treated only with vehicle. However, when analyzing dendritic morphology of hippocampal granular neurons in these animals, CBL appeared to attenuate dendritic deterioration caused by epilepsy, which was associated with improved cognitive performance of the CBL-treated animals in the BMT compared with vehicle-treated epileptic rats. In conclusion, although CBL did not exert an anticonvulsant effect against secondarily generalized seizures, it can be proposed for use as an add-on therapy in epilepsy management to prevent neuronal alterations, and to improve memory and learning processes. • Cerebrolysin is a mixture of peptides with neuroprotective and neurotrophic functions. • The hippocampus, a structure relevant to memory, is particularly affected by seizures. • Cerebrolysin attenuated hippocampal granular neuron deterioration caused by epilepsy. • Epileptic cerebrolysin-treated rats improved cognitive performance in the Barnes maze. • Cerebrolysin did not exert an anticonvulsant effect against secondarily generalized seizures. [ABSTRACT FROM AUTHOR]

Diabetes significantly increases the risk of stroke and post-stroke mortality. Recurrent hypoglycemia (RH) is common among diabetes patients owing to glucose-lowering therapies. Earlier, we showed that RH in a rat model of insulin-dependent diabetes exacerbates cerebral ischemic damage. Impaired mitochondrial function has been implicated as a central player in the development of cerebral ischemic damage. Hypoglycemia is also known to affect mitochondrial functioning. The present study tested the hypothesis that prior exposure of insulin-treated diabetic (ITD) rats to RH exacerbates brain damage via enhanced post-ischemic mitochondrial dysfunction. In a rat model of streptozotocin-induced diabetes, we evaluated post-ischemic mitochondrial function in RH-exposed ITD rats. Rats were exposed to five episodes of moderate hypoglycemia prior to the induction of cerebral ischemia. We also evaluated the impact of RH, both alone and in combination with cerebral ischemia, on cognitive function using the Barnes circular platform maze test. We observed that RH exposure to ITD rats leads to increased cerebral ischemic damage and decreased mitochondrial complex I activity. Exposure of ITD rats to RH impaired spatial learning and memory. Our results demonstrate that RH exposure to ITD rats potentially increases post-ischemic damage via enhanced post-ischemic mitochondrial dysfunction. [ABSTRACT FROM AUTHOR]

Experimental rat models of stroke and hemorrhage are important tools to investigate cerebrovascular disease pathophysiology mechanisms, yet how significant patterns of functional impairment induced in various models of stroke are related to changes in connectivity at the level of neuronal populations and mesoscopic parcellations of rat brains remain unresolved. To address this gap in knowledge, we employed two middle cerebral artery occlusion models and one intracerebral hemorrhage model with variant extent and location of neuronal dysfunction. Motor and spatial memory function was assessed and the level of hippocampal activation via Fos immunohistochemistry. Contribution of connectivity change to functional impairment was analyzed for connection similarities, graph distances and spatial distances as well as the importance of regions in terms of network architecture based on the neuroVIISAS rat connectome. We found that functional impairment correlated with not only the extent but also the locations of the injury among the models. In addition, via coactivation analysis in dynamic rat brain models, we found that lesioned regions led to stronger coactivations with motor function and spatial learning regions than with other unaffected regions of the connectome. Dynamic modeling with the weighted bilateral connectome detected changes in signal propagation in the remote hippocampus in all 3 stroke types, predicting the extent of hippocampal hypoactivation and impairment in spatial learning and memory function. Our study provides a comprehensive analytical framework in predictive identification of remote regions not directly altered by stroke events and their functional implication., Competing Interests: Disclosure/Conflict of Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Current antipsychotics have limited effects on the cognitive deficits of schizophrenia patients, therefore, cognitive remediation has been applied to schizophrenia patients to ameliorate cognitive dysfunction. However, the neurobiological mechanisms of cognitive training programs have not been well studied because established animal models are not suitable or because repetitive training has not been introduced in such animal models. In the present study, we employed Toll-like receptor 2 knockout (TLR2 KO) mouse as a schizophrenia mouse model and evaluated the effects of repetitive training as cognitive remediation therapy for schizophrenia. TLR2 KO mice could fully learn the Barnes maze paradigm through repetitive training to improve memory retrieval and reversal learning ability, although the learning speed was slower than that of wild-type (WT) animals. In addition, highly repetitive training activated the neuronal cells in the prefrontal cortex, hippocampal CA3 and hippocampal DG regions of TLR2 KO mice, similar to WT mice. These results indicated that TLR2 KO mouse would be a useful tool for studying the neurobiological mechanisms of cognitive remediation in schizophrenia. [ABSTRACT FROM AUTHOR]