Behavioral and Cognitive Consequences of Obesity in Parents and Offspring in Female and Male Rats: Implications of Neuroinflammation and Neuromodulation.

Obesity is a rapidly growing public health concern that can create a family-wise burden. This study was aimed to investigate behavioral, cognitive, neuroinflammatory, and neuromodulatory consequences of the diet and parental obesity. Female and male Wistar albino rats were fed on either an obesogenic or standard diet for 12 weeks, beginning with weaning. Thereafter, the animals were matched and allowed to mate. Pups born to obese or normal parents received either the diet or standard chow to the same age. The obesogenic diet and/or parental obesity increased the locomotor activity in both females and males. The diet exhibited anxiolytic-like and antidepressant-like properties, and impaired short-term object memory as well as spatial memory. Interestingly, the obesogenic diet resulted in neuroinflammation only in naïve animals, but not in the ones with parental obesity. BDNF, SIRT1, and p53 expressions were decreased, whereas RelN expression was increased in the brain with the diet, regardless of parental obesity. Multi-factor analyses demonstrated that the obesogenic diet is the prominent influencer of cognitive, neuroinflammatory, and neuromodulatory results while parental obesity has an effect on spatial memory, neuroinflammation, and hippocampal RelN and p53 expressions. Here, we provided supporting evidence for detrimental cognitive and neuroinflammatory consequences of early life consumption of the obesogenic diet which accompanies alterations in neuromodulatory factors. Surprisingly, the diet was found beneficial against anxiety-like and depression-like behaviors, and additionally, parental obesity was demonstrated to impair some aspects of cognitive performance which appears unrelated to neuroinflammation.

CREB1 and PPAR-α/γ Pathways in Hepatic Ischemia/Reperfusion: Route for Curcumin to Hepatoprotection.

Background: Hepatic ischemia/reperfusion injury is a major problem that can exacerbate complications, particularly in liver transplantations. Objectives: This study aimed to investigate the cellular mechanisms of ischemia/reperfusion injury and hepatoprotection by curcumin. Methods: Wistar albino rats were divided into four groups as Control, Sham, I/R, and Cur+I/R. Hepatic ischemia/reperfusion was induced in I/R and Cur+I/R animals, the latter of which was also given 50 mg/kg/day of curcumin for 14 days. Liver aminotransferases and the transcription regulators of inflammation (RelA, IκB, PPAR-α, PPAR-γ, CREB1) were examined along with the histological examination. Results: Hepatic ischemia/reperfusion was found to disrupt hepatic microstructure and downregulate PPAR-α, PPAR-γ, and CREB1 transcripts. Curcumin supplementation in hepatic ischemia/reperfusion recovered the structural organization and promoted the hepatocyte regeneration while increasing expressions of PPARs and CREB1. RelA and IκB were found unaltered, possibly due to the crosstalk between targeted transcripts by ischemia/reperfusion and curcumin. Conclusions: In sum, PPAR-α/γ and CREB1 were involved in hepatic ischemia/reperfusion and, moreover, were detected to be stimulated by curcumin. PPAR and CREB pathways were found to provide a route to hepatoprotection for curcumin supplementation as evidenced by the microstructural improvement.

Platelet-Rich Plasma (PRP) is a Potential Self-Sourced Cognition Booster in Elderly Mice.

Background: A complex set of neurotrophic growth factors participates in neuroplasticity in the aging brain. Platelets are a copious source of growth factors, most of which display also the neurotropic activity. On this basis, we investigated behavioral and cognitive consequences of the administration of intravenous allogeneic platelet-rich plasma (PRP) in senescent mice.Methods: The animals (16-18 months old) were injected with either physiological saline or PRP which was acquired from age-matched counterparts and subjected to a battery of tests comprised of open-field, elevated-plus maze, tail suspension, and Morris water maze test.Results: We found that PRP treatment increases locomotion and improves learning and memory in elderly mice. Importantly, the PRP-treated animals did not exhibit any anxiety- or depression-like behaviors.Conclusion: The present study is the first to demonstrate that allogeneic PRP possesses beneficial effects against cognitive aging and it signifies that PRP may be used as a novel self-sourced treatment in age-related cognitive decline.

Anticonvulsive and behavior modulating effects of sophoretin and rutoside.

INTRODUCTION: Seizures are the hallmarks of most types of epilepsies. Behavioral and cognitive impairments coincide with interictal periods even though it is not clear whether these impairments spring out of the seizure itself or accompanying sociopsychological burden of the disease. MATERIALS AND METHODS: In this study, we investigated behavioral and cognitive consequences of a single GABA receptor-related seizure in mice, and examined the potential anticonvulsive and behavior-modulating properties of sophoretin (quercetin) and rutoside (rutin). RESULTS: The study demonstrated that sophoretin and rutoside, common flavonoids of the human diet, delay the seizure onset and reduce the seizure stage. Moreover, they exerted an antidepressant-like effect, which was independent of the seizure. Neither treatments nor seizure altered recognition and spatial memory performances of the mice. CONCLUSIONS: Behavioral or cognitive disturbances that are evident in epileptic patients did not appear following a single seizure. In addition, we suggest that both sophoretin and rutoside successfully alleviate the seizure severity without interfering in the behavioral stability and cognitive performance. Hence, these flavonoids may be of use as adjuncts to the current treatment options.

Chia seed ( Salvia hispanica L. ) supplementation may contribute to raising the levels of vitamin B12: an option for the vegan diet / Suplementação de semente de chia ( Salvia hispanica L. ) pode contribuir para elevar os níveis de vitamina B12: uma opção para a dieta vegana

ABSTRACT Objective The chia seed, an ancient pseudocereal, is rich in omega-3 fatty acids and polyphenols, and has been suggested to possess several health benefits. Although it has gained popularity among nutritionists, little is known about the systemic effects of chia and their interactions. Hence, hepatorenal indicators and plasma vitamin concentrations in chia-supplemented aluminum-exposed rats were investigated. Methods Wistar albino rats were either fed on a chia-rich- or standard-diet for 21 days and exposed to aluminum. Liver function tests (Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase, Lactate Dehydrogenase), kidney function tests (Urea Nitrogen, Creatinine), and vitamin B12 and folic acid measurements were performed by using an automated analyzer. Results Aluminum exposure had no influence on renal function, as did chia supplementation. However, liver function was disturbed with the exposure to Aluminum and chia was of no use against it. Surprisingly, it was found that the animals fed on a chia-rich diet displayed higher concentrations of vitamin B12 which was not the case for folic acid. Conclusion It was deduced that a chia-rich diet has no effect on the renal function and is not able to reverse aluminum-induced hepatotoxicity; however, it may be of benefit against vitamin B12 insufficiency and thus, it may offer a novel treatment option which is particularly important in the vegan diet.

RESUMO Objetivo A semente de chia, um antigo pseudocereal, é rica em ácidos graxos ômega-3 e polifenóis e tem sido sugerida como tendo vários benefícios para a saúde. Embora tenha ganhado popularidade entre os nutricionistas, na verdade, pouco se sabe sobre os efeitos e interações sistêmicas da chia. Assim, investigamos os indicadores hepatorrenais e as concentrações plasmáticas de vitamina em ratos expostos ao alumínio suplementados com chia. Métodos Ratos albinos Wistar foram alimentados com dieta rica em chia ou padrão por 21 dias e expostos ao alumínio. Testes de função hepática (Alanina Aminotransferase, Aspartato Aminotransferase, Fosfatase Alcalina, Lactato Desidrogenase), testes de função renal (ácido úrico, Creatinina) e medições de vitamina B12 e ácido fólico realizada usando um analisador automático. Resultados A exposição ao alumínio não influenciou a função renal, assim como a suplementação de chia. No entanto, a função hepática foi perturbada com a exposição e a chia foi inútil contra ela. Surpreendentemente, descobrimos que os animais que se alimentavam de uma dieta rica em chia apresentavam concentrações mais elevadas de vitamina B12, o que não era o caso do ácido fólico. Conclusão Deduzimos que a dieta rica em chia não tem efeito sobre a função renal e não é capaz de reverter a hepatotoxicidade induzida pelo alumínio; no entanto, pode ser benéfico contra a insuficiência de vitamina B12 e, portanto, pode oferecer uma nova opção de tratamento que é particularmente importante na dieta vegana.

Detrimental effects of chia (Salvia hispanica L.) seeds on learning and memory in aluminum chloride­induced experimental Alzheimer's disease.

Polyphenols and omega­3 fatty acids are thought to have beneficial effects in Alzheimer's disease, the most common cause of dementia. Seeds of chia (Salvia hispanica L.) are highly rich in these nutrients, and thus, the present study investigated the effects of chia seeds on behavior and cognition in an aluminum­induced Alzheimer's disease model in rats. Experimental animals received chia supplementation either during the generation of the model (i.e., pretreatment) or after the model was established (i.e., treatment). A battery of behavioral and cognitive tests were performed, including open­field, elevated plus maze, Porsolt's forced swim, and Morris' water maze, to evaluate anxiety­ and depression­like behaviors, and learning and memory. Results showed that chia supplementation was ineffective against Alzheimer's­related anxiety, whereas depression­like behaviors were attenuated with both pretreatment and treatment. There was no improvement in learning and memory with chia treatment. Rather, cognitive performance in chia­pretreated animals was remarkably worse as compared to their non­treated disease­induced counterparts. Hippocampal concentrations of amyloid-ß42, amyloid precursor protein, and total tau protein were similarly increased in all disease­induced animals (despite chia supplementation), as compared to the controls. Based on these findings, chia supplementation during the progression of Alzheimer's disease may exacerbate the disease. Although the results presented here emerge from an experimental/preclinical study, we suggest cautious and careful use of chia, especially in early­stage Alzheimer's patients, until future research in different experimental settings is conducted.

Lecture attendance improves success in medical physiology.

The educators have underlined the importance of lecture attendance for decades. Nowadays, students have ample online educational sources, which began a debate on the necessity of in-class lectures. In the present study, we investigated the influence of lecture attendance on the exam success. To this aim, we adopted a novel approach and matched second-year medicine students' answers in three interim exams with the lectures related to those questions. Thereby, we were able to evaluate if attending lectures increases the chance of giving a correct answer to the exam question generated from the attended lecture. Furthermore, we examined students who had never taken the course before (first-time takers) and students who had failed and repeated the course (repeat takers) separately, since repeat takers may have attended a lecture previously. We found that first-time takers attended more lectures and gained higher total scores than repeat takers. Lecture-matched correct answers were significantly higher for attended lectures than for skipped lectures in all interim exams. Moreover, the correlation analyses revealed that the number of correct answers increases by lecture attendance in both first-time and repeat takers. These results indicate that in-class lectures still should be considered as an essential part of the medical physiology education, even in the internet era.

3',4'-Dihydroxyflavonol attenuates spatial learning and memory impairments in global cerebral ischemia.

OBJECTIVES: In the present study, effects of 3',4'-dihydroxyflavonol (DiOHF) on anxiety-like behavior, and learning and memory were investigated in a model of transient global cerebral ischemia and reperfusion. METHODS: The animals were assigned to sham-operated, ischemia, and two DiOHF-treated (10 mg/kg i.p.) groups. DiOHF was administered at 1 hour before and immediately after the ischemia. Male rats were subjected to bilateral common carotid artery occlusion to induce acute cerebral ischemia for 20 minutes, followed by reperfusion for 7 days. The openfield, elevated plus maze (EPM), and Morris water maze tests were used to evaluate the effects of DiOHF treatment on ischemia-induced locomotor activity, anxiety-like behavior, and spatial and recognition memory impairments, respectively. RESULTS: In the open field test, locomotor activity in the ischemic rats was not altered 6 days after the ischemia, nor was anxiety-like behavior, which was evaluated with the EPM (P > 0.05). In the water-maze test, cerebral ischemia significantly decreased the exploration time in the target quadrant, and the platform crossing counts were lower (P < 0.05) in the probe trial test; this memory impairment was significantly improved by DiOHF applied 1 hour before and immediately after ischemia (P < 0.05). DISCUSSION: All together, these findings suggest that DiOHF reverses spatial learning and memory deficits resulting from transient global ischemia but has no significant effect on anxiety-like behavior.

Impact of enriched environment on production of tau, amyloid precursor protein and, amyloid-ß peptide in high-fat and high-sucrose-fed rats.

OBJECTIVE: The Western-type diet is associated with an elevated risk of Alzheimer's disease and other milder forms of cognitive impairment. The aim of the present study was to investigate the effects of the environmental enrichment on amyloid and tau pathology in high-fat and high-sucrose-fed rats. METHODS: In total, 40 adult male rats were categorised into two main groups according to their housing conditions: enriched environment (EE, n=16) and standard housing condition (n=24). The groups were further divided into five subgroups that received standard diet, high-fat diet, and high-sucrose diet. We performed the analysis of amyloid ß-peptide (Aß) (1-40), Aß(1-42), amyloid precursor protein (APP), and tau levels in the hippocampus of rats that were maintained under standard housing conditions or exposed to an EE. RESULTS: The EE decreased the Aß(1-40), Aß(1-42), APP, and tau levels in high-fat and high-sucrose-fed rats. CONCLUSION: This observation shows that EE may rescue diet-induced amyloid and tau pathology.

Environmental enrichment reverses cognitive impairments provoked by Western diet in rats: Role of corticosteroid receptors.

AIMS: Previous studies demonstrated that the Western diet (WD), which is rich in saturated fat (HFD) and refined sugar (HSU), is related to the impairments of hippocampus-dependent learning and memory and forebrain synaptic plasticity in rodents. The environmental enrichment (EE) has been shown to enhance learning and memory in the HFD-induced cognitive deficits, but the exact mechanism is still not clearly understood. Therefore, the present study aimed to clarify the effects of the EE on spatial memory in WD-fed rats, and to analyze the potential role of corticosteroid receptors in the EE conditioning. MAIN METHODS: Male Wistar albino rats were housed in either an enriched or standard environment and fed with the HFD (35% of energy as fat), HSU (100% of carbohydrate as sucrose) or standard rat chow for 4weeks. We used the Morris' water maze test (MWM) to assess the learning and memory performance, and measured plasma levels of corticosterone (CORT) and adrenocorticotropic hormone (ACTH), as well as glucocorticoid (GR) and mineralocorticoid receptor (MR) levels in the hippocampus. KEY FINDINGS: The results showed that HFD-fed rats displayed poorer learning and memory performance evaluated with MWM than controls. The EE reversed the cognitive deficits caused by the HFD. In addition, the EE resulted in an increase of GR and MR levels without affecting plasma CORT and ACTH concentrations. SIGNIFICANCE: Based on these findings, it could be suggested that the EE plays an important role in amelioration of the HFD-induced cognitive impairments, but this intervention is independent of the hypothalamic-pituitary-adrenal axis and hippocampal corticosteroid receptor levels.

Antidepressant-like effects of quercetin in diabetic rats are independent of hypothalamic-pituitary-adrenal axis.

OBJECTIVE: Quercetin, one of the most potent flavonol in the family of flavonoids, has been shown to have benefits against diabetes and its complications. In the present study, we investigated effects of quercetin on depression-like behaviours and hypothalamic-pituitary-adrenal (HPA) axis in diabetic rats. METHODS: Experimental diabetes was induced by using streptozotocin, and either 50 or 100 mg/kg quercetin was intraperitoneally administered for 21 days. Following the last treatment, animals were subjected to the forced swim test, and subsequently, the blood was obtained by cardiac puncture to measure plasma adrenocorticotropic hormone (ACTH) and corticosterone (CORT) levels. RESULTS: A significant increase of the total immobile time, accompanied by a decrease in the immobility latency, which suggests a depressive status, was observed in diabetic animals that was reversed by the treatment of 50 mg/kg quercetin. However, the higher dose of quercetin (100 mg/kg) was ineffective in alleviating depression-like behaviours. The plasma concentrations of ACTH, and total- and free-CORT were not affected by both doses of quercetin. CONCLUSION: Therefore, we concluded that the antidepressant-like effects of quercetin in diabetes are independent of the HPA axis.

Curcumin alleviates cisplatin-induced learning and memory impairments.

The present study has been designed to investigate the role of curcumin on cisplatin-inducedcognitive impairment and to reveal mechanisms of cisplatin's detrimental actions on cognition in rats. Animals were treated with cisplatin (5mg/kg/week) and/or curcumin (300mg/kg/day) for 5weeks. Morris water maze test was used to assess spatial learning and memory. Enzymatic activities of acetylcholinesterase (AChE) and superoxide dismutase (SOD) were evaluated from hippocampus and plasma samples, and malondialdehyde (MDA), which is the end-product of lipid peroxidation, was determined by a colorimetric method. Our results showed that cisplatin (5mg/kg/week, 5weeks) caused learning and memory deficits, elevated MDA content, decreased SOD activity in the hippocampus and plasma, and AChE activity in the hippocampus. Curcumin improved learning and memory in rats with administration of cisplatin. In addition, curcumin significantly reduced the level of MDA and increased the activities of SOD and AChE. Taken together, our findings indicate that curcumin ameliorates cisplatin-induced spatial learning and memory impairment, possibly through restored cholinergic function and enhanced oxidative status.