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Various studies suggested that neuroinflammation leads to the development of several neurodegenerative disorders like Parkinson's disease (PD), Alzheimer's disease (AD), and Huntington's disease (HD). Rotenone is an organic pesticide and potent inhibitor of complex I of electron transport chain widely used to develop the PD model. Numerous studies reported rotenone toxicity in the dopaminergic system but very few studies are available on rotenone‐induced glial cell activation and subsequent neurodegeneration and alterations in various types of behavior. Therefore, the present study was designed to explore the effect of rotenone on neuroinflammation and its deleterious effect on the behavior of mice, and also how these effects can be protected through quercetin. Quercetin, a natural flavonoid having strong antioxidant and anti‐inflammatory properties, is found in vegetables and fruits. The finding of the study indicated that rotenone 5 mg/kg body weight for 60 days through oral gavage leads to the release of inflammatory markers in blood serum, astrocytes activation in substantia nigra and hippocampus, and subsequently decreased density of dopaminergic fibers in the striatum. Rotenone also altered the memory of the mice as indicated by decreased spontaneous alteration in Y‐maze and T‐maze tests and reduction in exploration time in novel object recognition, increased immobility time in the forced swim test and reduced muscular strength. Co‐treatment of quercetin 30 mg/kg/day through oral gavage for 60 days along with rotenone significantly reversed all these adverse effects, suggesting that quercetin could reduce neuroinflammation, and improve memory, and cognitive function. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive decline in cognitive function. Type 2 diabetes mellitus (T2DM) is an important risk factor for AD. Glucose-dependent insulinotropic polypeptide (GIP) has been identified to be effective in T2DM treatment and neuroprotection.Objective: The present study investigated the neuroprotective effects and possible mechanisms of DAla2GIP-Glu-PAL, a novel long-lasting GIP analogue, in APP/PS1 AD mice.Methods: Multiple behavioral tests were performed to examine the cognitive function of mice. In vivo hippocampus late-phase long-term potentiation (L-LTP) was recorded to reflect synaptic plasticity. Immunohistochemistry and immunofluorescence were used to examine the Aβ plaques and neuroinflammation in the brain. IL-1β, TNF-α, and cAMP/PKA/CREB signal molecules were also detected by ELISA or western blotting.Results: DAla2GIP-Glu-PAL increased recognition index (RI) of APP/PS1 mice in novel object recognition test, elevated spontaneous alternation percentage of APP/PS1 mice in Y maze test, and increased target quadrant swimming time of APP/PS1 mice in Morris water maze test. DAla2GIP-Glu-PAL treatment enhanced in vivo L-LTP of APP/PS1 mice. DAla2GIP-Glu-PAL significantly reduced Aβ deposition, inhibited astrocyte and microglia proliferation, and weakened IL-1β and TNF-α secretion. DAla2GIP-Glu-PAL also upregulated cAMP/PKA/CREB signal transduction and inhibited NF-κB activation in the hippocampus of APP/PS1 mice.Conclusion: DAla2GIP-Glu-PAL can improve cognitive behavior, synaptic plasticity, and central pathological damage in APP/PS1 mice, which might be associated with the inhibition of neuroinflammation, as well as upregulation of cAMP-/PKA/CREB signaling pathway. This study suggests a potential benefit of DAla2GIP-Glu-PAL in the treatment of AD. [ABSTRACT FROM AUTHOR]

This study aims to investigate the problem-solving behaviors of a teacher and his students based on a cognitive--metacognitive framework. The problem-solving behaviors of 6--8th-grade students and a mathematics teacher were recorded and encoded during task-based interview sessions about solving problems, and semi-structured interviews were used to obtain information regarding the mathematics teacher's perceptions of mathematical problem-solving processes. They solved the problems in a learning environment, and their problem-solving processes were investigated using the think-aloud method. The results indicated that the students and the teacher followed a similar path involving reading, understanding, exploring, planning, and implementing. Furthermore, not all episodes occurred in each problem-solving task and the behaviors that represented given episodes changed according to the participants. Students with different problem-solving skill levels were found to exhibit different frequencies of cognitive and metacognitive behaviors while solving problems. The problem-solving behaviors of the teacher and the students revealed information related to metacognitive behaviors that are to be developed in further studies. [ABSTRACT FROM AUTHOR]

The adolescent brain is vulnerable to long‐lasting cognitive disturbances resulting from nicotine exposure. Although exercise has been used as an intervention for ameliorating cognitive deficits in various disorders, the effect on cognitive changes induced by nicotine exposure and its underlying mechanisms remain unclear. The purpose of this study was to investigate the effects of exercise on nicotine reward‐associated cognitive behaviors in adolescent rats subjected to nicotine conditioned place preference paradigm (CPP). Male adolescent rats were trained on the Go/NoGo task, then subjected to nicotine CPP, and then randomly separated into four groups: sedentary (SED), high‐ (HE), moderate‐ (ME), and low‐intensity (LE) exercise. Rats in exercise groups performed treadmill running 30 min daily for 10 days. Results showed that MEs had shorter escape latencies in the Morris water maze (MWM) test compared to SEDs. Although time spent and distance swam in the target quadrant significantly increased in both the MEs and HEs, the number of target quadrant crosses increased significantly only in MEs. MEs and HEs showed higher performance accuracy on NoGo and lower scores on CPP tasks. Expression of α7 nicotinic acetylcholine receptors (nAChRs) and downstream signaling molecules increased in MEs in prefrontal cortex but not hippocampus, with α7 nAChRs expression positively associated with NoGo accuracy and MWM probe test performance, but negatively correlated with CPP scores. The findings of this study suggest that moderate‐intensity exercise can improve nicotine induced cognitive behaviors, and implicates prefrontal cortical α7 nAChR‐mediated signal transduction as a possible mechanism. [ABSTRACT FROM AUTHOR]

Neurodegenerative disorders, such as Alzheimer's disease (AD), have the gradual onset of neurobiological changes preceding clinical diagnosis by decades. To elucidate how brain dysfunction proceeds in neurodegenerative disorders, we performed longitudinal characterization of behavioral, morphological, and transcriptomic changes in a tauopathy mouse model, P301S transgenic mice. P301S mice exhibited cognitive deficits as early as 3 months old, and deficits in social preference and social cognition at 5-6 months. They had a significant decrease of arborization in basal dendrites of hippocampal pyramidal neurons from 3 months and apical dendrites of PFC pyramidal neurons at 9 months. Transcriptomic analysis of genome-wide changes revealed the enrichment of synaptic gene upregulation at 3 months of age, while most of these synaptic genes were downregulated in PFC and hippocampus of P301S mice at 9 months. These time-dependent changes in gene expression may lead to progressive alterations of neuronal structure and function, resulting in the manifestation of behavioral symptoms in tauopathies.

Abstract intelligence is the human enquiry of both natural and artificial intelligence at the neural, cognitive, functional, and logical levels reductively from the bottom up. According to the abstract intelligence theory, a cognitive robot is an autonomous robot that is capable of thought, perception, and learning based on the three-level computational intelligence known as the imperative, autonomic, and cognitive intelligence. This paper presents the theoretical foundations of cognitive robots based on the latest advances in abstract intelligence, cognitive informatics, and denotational mathematics. A formal model of intelligence known as the Generic Abstract Intelligence Mode (GAIM) is developed, which provides a foundation to explain the mechanisms of advanced natural intelligence such as thinking, learning, and inference. A set of denotational mathematics is introduced for rigorously modeling and manipulating the behaviors of cognitive robots. A case study on applications of a denotational mathematics, visual semantic algebra (VSA), is presented in architectural and behavioral modeling of cognitive robots based on the theory of abstract intelligence.

Little information is available on infant behavioral development outcomes of prenatal iodine supplementation in regions of mild to moderate iodine deficiency. Studies performed to date, all of which relied on global developmental assessments, have yielded inconsistent findings with regard to psychomotor development, negative findings with regard to mental development, and no information as to the development of specific cognitive functions. Our review of these studies leads us to suspect that the use of global developmental assessments might partially explain the negative and inconsistent findings. To identify cognitive processes that might be sensitive to prenatal iodine supplementation, we examined the timing of thyroid hormone action on specific brain systems. The development of infant visual attention is sensitive to thyroid hormone during the early prenatal period, when the fetus is entirely dependent on maternal thyroid hormone. For this reason, infant visual attention has the potential to be a sensitive measure of infant outcomes in prenatal iodine supplementation studies. We suggest the assessment of infant visual attention, with follow-up examination of childhood executive functions, as a means of capturing the effects of maternal iodine deficiency and prenatal iodine supplementation on specific cognitive processes. In particular, we propose comparison of infant performance on global developmental tests and specialized tests of visual attention in pilot trials of prenatal iodine supplementation in regions of mild to moderate iodine deficiency. Only by comparing the 2 types of tests side by side will it be possible to establish whether the use of a sensitive measure of infant visual attention will increase the reliability of such supplementation studies. Recognizing that exposure misclassification may also provide a partial explanation for the inconsistent neurodevelopmental outcomes in previous studies, we suggest that urinary iodine concentration or creatinine-corrected iodine excretion be monitored regularly in such trials throughout the prenatal period. [ABSTRACT FROM AUTHOR]

Cognitive deficits have an extensive influence on the quality of life of the Parkinson’s disease (PD) patients. Previous studies have shown that lack of steroid hormones have an important role in the development of PD. Therefore, in this study the effects of neurosteroid allopregnanolone (Allo) on the PD-induced cognitive disorders were assessed. To simulate PD, 6-hydroxydopamine (6-OHDA) was injected into the rat’s substantia nigra. Allo (5 and 20 mg/kg, orally) were administered on the day after the 6-OHDA injection and continued during the entire treatment period (two months). Cognitive behaviors were assessed by Moris water maze (MWM), novel object recognition (NOR) and object location tasks . The data indicated that Allo significantly improved the 6-OHDA-induced cognitive impairment which revealed by the reduction of time spent to find out platform (escape latency) and the increase of retention time in MWM test and also with increase in the exploration index in NOR and object location tasks . Present study strongly supports the pro-cognitive property of allopregnanolone in PD. [ABSTRACT FROM AUTHOR]

This study assessed the effects of single or combined administration of temozolomide (TMZ) and interferon-gamma (IFN-ᵞ) on anxiety-like behaviors, balance disorders, learning and memory, TNF-α, IL-10, some oxidant and antioxidants factors with investigating the toll-like receptor-4 (TLR4) and p-CREB signaling pathway in C6-induced glioblastoma of rats. 40 male Sprague-Dawley rats bearing intra-caudate nucleus (CN) culture medium or C6 inoculation were randomly divided into five groups as follows: Sham, Tumor, TMZ, IFN-ᵞ and a TMZ + IFN-ᵞ combination. The open-field test (OFT), elevated plus maze (EPM), rotarod, and passive avoidance test (PAT) were done on days 14–17. On day 17 after tumor implantation, brain tissues were extracted for histopathological evaluation. TNF-α, IL-10, SOD, GPX, TAC, MDA, the protein level of TLR4 and p-CREB was measured. Combination therapy inhibited the growth of the tumor. Treatment groups alleviated tumor-induced anxiety-like behaviors and improved imbalance and memory impairment. SOD, GPX, and TAC decreased in the tumor group. The combination group augmented GPX and TAC. MDA decreased in treatment groups. TMZ, IFN-ᵞ reduced tumor-increased TNF-α and IL-10 level. The combination group declined TNF-α level in serum and IL-10 level in serum and brain. Glioblastoma induced significant upregulation of TLR4 and p-CREB in the brain which inhibited by IFN-ᵞ and TMZ+ IFN-ᵞ. The beneficial effects of TMZ, IFN-ᵞ, and TMZ+ IFN-ᵞ on neurocognitive functioning of rats with C6-induced glioblastoma may be mediated via modulating oxidative stress, reduced cytokines, and the downregulation of expression of TLR4 and p-CREB. Combination treatment appears to be more effective than single treatment. [Display omitted] [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a multi-faceted neurodegenerative disorder that leads to drastic cognitive impairments culminating in death. Pathologically, it is characterized by amyloid-β (Aβ) plaques, neurofibrillary tangles and neurodegeneration in brain. Complete cure of AD remains elusive to date. Available synthetic drugs only provide symptomatic reliefs targeting single molecule, hence, are unable to address the multi-factorial aspects in AD pathogenesis. It is imperative to develop combinatorial drugs that address the multiple molecular targets in AD. We show a unique polyherbal formulation of Brahmi, Mandukaparni, Shankhpushpi, Yastimadhu, Kokilaksha and Shunthi called 'Medha Plus' (MP), conventionally used for improving memory and reducing anxiety, was able to ameliorate cognitive deficits and associated pathological hallmarks of AD. Viability assays revealed that MP prevented Aβ-induced loss of neurites as well as neuronal apoptosis in cellular models. An array of behavioral studies showed that MP was able to recover AD-associated memory deficits in both Aβ-injected rats and 5XFAD mice. Immunohistochemical studies further revealed that MP treatment reduced Aβ depositshpi and decreased apoptotic cell death in the hippocampus. Enzymatic assays demonstrated anti-oxidative and anti-acetyl cholinesterase properties of MP especially in hippocampus of Aβ-injected rats. An underlying improvement in synaptic plasticity was observed with MP treatment in 5XFAD mice along with an increased expression of phospho-Akt at serine 473 indicating a role of PI3K/Akt signaling in correcting these synaptic deficits. Thus, our strong experiment-driven approach shows that MP is an incredible combinatorial drug that targets multiple molecular targets with exemplary neuroprotective properties and is proposed for clinical trial. [Display omitted] • Polyherbal formulation Medha Plus (MP) attenuates Aβ accumulation in Aβ-infused rodents. • AChE activity and mitochondrial ROS generation was attenuated by MP. • MP restores the pre- and post-synaptic markers in 5xFAD mice. • MP enhances the phosphorylation of Akt in AD models. • MP protects neurons from Aβ induced toxicity leading to restoration of memory in AD rodents. [ABSTRACT FROM AUTHOR]

Gestational nicotine exposure is associated with cognitive abnormalities in young offspring. However, practical strategies for prevention or treatment of impaired cognitive behaviors of offspring are not available due to the lack of systematic investigation of underlying mechanism. Therefore, this study aimed at examining the effects of gestational and/or perinatal nicotine exposure (GPNE) on cognitive behaviors in offspring of C57BL/6J mice to provide systematic behavioral data. Pregnant mice were exposed to nicotine via sweetened drinking water during six time-windows, including gestational day 0 to day 13 (G0–G13), G14–postnatal day 0 (P0), G0–P0, G14–P7, G0–P7, and P0–P7. During P42–P56 days, both male and female offspring were given a battery of behavioral tests. Depending on the time of exposure, GPNE impaired working memory, object-based attention, and prepulse inhibition in male and female offspring to different extents. Nicotine exposure during G14–P0 also decreased norepinephrine turnover in the prefrontal cortex on P28 and P56. Overall results indicate that nicotine exposure during any time-windows of development impairs cognitive behaviors in offspring, and suggest that certain time-windows, e.g., G14–P0, should be selected for further studies on the underlying neurochemical or molecular mechanisms. [ABSTRACT FROM AUTHOR]

Abstract: Aluminum (Al) is a known neurotoxicant and circumstantial evidence has linked this metal with several neurodegenerative disorders like Alzheimer''s disease, but no causal relationship has yet been proved. Al-induced behavioral alterations as well as cognitive deficits and rodent brain neurotransmitter level, are well known in adults but the exact mechanism in the offspring of perinatally Al exposed dams is not yet understood properly and needs more attention. In the present study, the perinatal oral exposure of the dams to 300 and 600mg/kg/day Al (aluminum chloride) resulted in significant and deleterious effects in the offspring inflicting a dose-dependent reduction in postnatal body weight gain, delays in opening of the eyes and appearance of body hair fuzz, and deficits in the sensory motor reflexes of the mice pups during weaning period (from the day of birth to postnatal day 21). During adolescent ages of the male offspring, a significant and dose-dependent deficit was also observed in their locomotor activity at postnatal day 22 (PD 22), learning capability (at PD 25), and cognitive behavior (at PD 30–36). Furthermore, a significant and dose-dependent disturbance in the levels of neurotransmitters like dopamine (DA) and serotonin (5-HT) was also observed in the forebrain region of the offspring at PD 7, PD 14, PD 21, PD 30, and PD 36. Thus, perinatal Al exposure, particularly during pregnancy and lactation period, can affect the in utero developing fetus and postnatal developing sucklings, raising the concerns that during a critical perinatal period of brain development, Al exposure has potential and long lasting neurotoxic hazards and might modify the properties of the dopaminergic system and thus can change the threshold of that system or other related systems at later ages. A reduced use of Al during pregnancy is of crucial importance in preventing Al-induced delayed neurotoxicity in the offspring. [Copyright &y& Elsevier]

CCK acts peripherally as a satiating peptide released during meals in response to lipid feeding and centrally functions in the modulation of feeding, exploratory, and memory activities. The present study determined metabolic parameters, food intake, anxiety-like behaviors, and cognitive function in mice lacking the CCK gene. We studied intestinal fat absorption, body composition, and food intake of CCK knockout (CCK-KO) mice by using the noninvasive measurement of intestinal fat absorption along with quantitative magnetic resonance (QMR) imaging and the DietMax system, respectively. Additionally, exploratory and memory capacities were assessed by monitoring running wheel activity and conducting elevated plus-maze and Morris water-maze tests with these mice. Compared with wild-type (WT) littermate controls, CCK-KO mice had normal food intake, fat absorption, body weight, and body mass. CCK-KO mice ate more food than control animals during the light period and less food during the dark period. Energy expenditure was unchanged between the genotypes; however, CCK-KO mice displayed greater fatty acid oxidation. CCK-KO mice were as active as WT animals in the running wheel test. CCK-KO mice spent more time in the closed arms of an elevated plus-maze, indicative of increased anxiety. Additionally, CCK-KO mice exhibited attenuated performance in a passive avoidance task and impaired spatial memory in the Morris water maze test. We conclude that CCK is involved in metabolic rate and is important for memory and exploration. CCK is intimately involved in multiple processes related to cognitive function and food intake regulation. [ABSTRACT FROM AUTHOR]

In this work the operation in situations of representation semiotic registries is observed. It is to say, how the learning of mathematical objects can be facilitated, in this case linear equations systems and the solution of the same one, making conjugate in a sequence situations that in addition imply work in different representation semiotic registries and passage among them. The sustenance to construct this sequence is the previous research on this area, on the observed phenomena relative to the use representation semiotic registries in the learning; on the necessity to raise to the student activities that induce it to pass by action situations, formulation and validation; and also those that explain problems relative to the learning of these mathematical objects. The objective is to elaborate and to probe a "quality" education sequence that facilitates the learning of linear equations systems and solution of the same one, and look for mathematical behaviors in the students task that facilitate the learning of the object and also to obtain cognitive behaviors doing that the treatment and the passage of representation semiotic registries are the axis around as the construction of the activities moves. [ABSTRACT FROM AUTHOR]

• Increase in pain sensitivity following chronic pain correlates with decline in attention. • A decrease in the activity of the LC-NE system ameliorated the poor attentional performance of neuropathic rats. • Treatments related to the NE system in subjects suffering from neuropathic pain may reduce the effects of chronic pain on attentional factors. Despite years of research on pain comorbidity with affective disorders and cognitive deficits, it is still unclear how deficit in attention co-occurs with chronic pain. It is likely that altered neuroplasticity and or dysregulated neurotransmitters induced by chronic pain, at which pain and cognitive processing systems overlap, may have a negative effect on cognitive processing such as attention. One of the main common networks involved in attentional and pain processing is the noradrenergic system originating from the locus coeruleus (LC). We hypothesized that heightened noradrenaline release from LC induced by chronic pain could cause a deficit in visual attention. For this purpose, performance on the 5-choice serial reaction time test (5-CSRTT) was tested in animals with and without a chronic constriction injury and a selective depletion of noradrenaline in the LC. In addition, pain sensitivity was measured via mechanical allodynia and thermal hyperalgesia. We found that the increase in pain sensitivity following chronic pain correlates with a decline in executive functions as measured by 5-CSRTT. This was true in conditions of both low and high attentional demand. Interestingly, a selective depletion of noradrenaline in LC improved the attentional deficits caused by chronic pain. We argue that changes to the noradrenergic system originating in LC can improve deficits in visual attention induced by chronic pain. Deficit in attention is a common comorbidity among patients with chronic pain which adversely affects them in their family and work lives. Patients struggle with functional impairment due to pain, and deficite in attention adds to this dysfunction. Our findings identify the NE-LC system as a key mediator between chronic pain and the attentional deficits associated with this. This finding calls for further investigations concerning treatments related to the noradrenergic system to reduce the malicious effects of chronic pain. [ABSTRACT FROM AUTHOR]