Comparison of HIIT and MICT and further detraining on metabolic syndrome and asprosin signaling pathway in metabolic syndrome model of rats.

Physical activity promotes various metabolic benefits by balancing pro and anti-inflammatory adipokines. Recent studies suggest that asprosin might be involved in progression of metabolic syndrome (MetS), however, the underlying mechanisms have not been understood yet. This study aimed to evaluate the effects of high-intensity interval training (HIIT), moderate-intensity continuous training (MICT), and further detraining on MetS indices, insulin resistance, serum and the liver levels of asprosin, and AMP-activated protein kinase (AMPK) pathway in menopause-induced MetS model of rats. A total of 64 Wistar rats were used in this study and divided into eight groups: Sham1, OVX1 (ovariectomized), Sham2, OVX2, OVX + HIIT, OVX + MICT, OVX + HIIT + Det (detraining), and OVX + MICT + Det. Animals performed the protocols, and then serum concentrations of asprosin, TNF-α, insulin, fasting blood glucose, and lipid profiles (TC, LDL, TG, and HDL) were assessed. Additionally, the liver expression of asprosin, AMPK, and P-AMPK was measured by western blotting. Both HIIT and MICT caused a significant decrease in weight, waist circumference, BMI (P = 0.001), and serum levels of glucose, insulin, asprosin (P = 0.001), triglyceride, total cholesterol, low-density lipoprotein (LDL), and TNF-α (P = 0.001), but an increase in the liver AMPK, P-AMPK, and P-AMPK/AMPK (P = 0.001), compared with OVX2 noexercised group. MICT was superior to HIIT in reducing serum asprosin, TNF-a, TG, LDL (P = 0.001), insulin, fasting blood glucose, HOMA-IR, and QUEKI index (P = 0.001), but an increase in the liver AMPK, and p-AMPK (P = 0.001). Although after two months of de-training almost all indices returned to the pre exercise values (P < 0.05). The findings suggest that MICT effectively alleviates MetS induced by menopause, at least partly through the activation of liver signaling of P-AMPK and the reduction of asprosin and TNF-α. These results have practical implications for the development of exercise interventions targeting MetS in menopausal individuals, emphasizing the potential benefits of MICT in mitigating MetS-related complications.

Metformin improves memory via AMPK/mTOR-dependent route in a rat model of Alzheimer's disease.

Objectives: Metformin, as an insulin sensitizer, is a familiar antidiabetic drug. Increasing evidence points to metformin's protective effects against Alzheimer's disease (AD). However, the mechanism is not well understood. The present study evaluated whether inhibiting AMPK and activating mTOR could stop metformin from improving memory in rats with streptozotocin (STZ) -induced Alzheimer's disease. Materials and Methods: Twelve-week-old Wistar rats, were injected 3 mg/kg STZ intracerebroventricularly on days 1 and 3 to develop the animal model. Metformin was applied orally at 100 mg/kg (17 days). Forty-five min before the retrieval phase, dorsomorphin (DM; AMPK inhibitor, 2 M) and MHY (mTOR activator, 0.1 M) were administered. Morris Water Maze (MWM) and shuttle box were utilized to measure spatial and passive avoidance memory, respectively. Congo red staining was used to identify cortical amyloid deposition. Results: The findings exhibited a considerable enhancement in spatial learning and memory in the metformin treatment group (P≤0.05). Injection of DM and MHY alone could not significantly change MWM and passive avoidance. Additionally, co-administration of DM and MHY increased escape latency (P≤0.001) and reduced the total time spent in the target quadrant (TTS) (P≤0.05) compared to the STZ+MET group during retrieval of MWM. Also, co-injection of DM and MHY increased step-through latency (STL) and decreased time spent in the dark compartment (TDC) compared to the STZ+MET group (P≤0.001). Conclusion: Metformin appears to have a therapeutic impact by activating AMPK and inactivating mTOR. As a result, it could be used as an Alzheimer's treatment strategy.

Therapeutic Effects Of Combined and Chronic Treatment of Tat-GluA23y and D-Serine on Cognitive Dysfunction in Postmenopausal Rats.

BACKGROUND: The incidence of Alzheimer's disease (AD) in female gender compared with male has been addressed as a health concern, particularly in menopausal age. We here hypothesized that co-administration of NMDARs agonist (D-serine) and AMPARs endocytosis inhibitor (Tat-GluA23y) might be a potential target for alleviating memory impairment in sporadic Alzheimer model of rats. METHODS: Forty-eight female Wistar rats weighing 200-220 randomly divided into six groups. One month later, ovariectomized rats underwent stereotaxic surgery and were cannulated into the brain lateral ventricles. Streptozotocin was injected (3 mg/kg), then animals received the related treatments until the day 51, which experienced acquisition of spatial memory in Morris Water Maze test. Finally, the level of phosphorylated cAMP response element binding protein (CREB) in the hippocampus was measured by Western blotting. RESULTS: Co-administration of D-serine and GluA23y significantly enhanced the acquisition and retrieval of impaired spatial memory in ovariectomized rats with AD (p < .001). Compared to Glu-A 23, D-serine caused more improvement in the mentioned parameters above, however, these values for both groups were still significantly different from the control group (P < .05). CONCLUSION: Simultaneous treatment with D-serine and GluA23y synergistically improved STZ induced spatial memory impairment in OVX rat, probably partly via increase in phosphorylated CREB protein.

Concurrent high-intensity interval training and probiotic supplementation improve associative memory via increase in insulin sensitivity in ovariectomized rats.

OBJECTIVES: Metabolic syndrome (MetS) is a serious concern among postmenopausal women which predisposes them to cardiovascular and cognitive disorders. Healthful diet and exercise training have been essential strategies to prevent the progress of MetS. The aim of this study was to evaluate the effect of supplementation with a native potential probiotic and high-intensity interval training (HIIT) for 8 weeks on retention of associative memory in rats with ovariectomy- induced metabolic syndrome. METHOD: Thirty-two female ovariectomized Wistar rats were divided into four groups (n = 8/group): Control (OVX + Veh), exercise (OVX + Exe), probiotic (OVX + Pro), exercise with probiotic (OVX + Exe + Pro). One sham surgery group was included as a control group. Animals received 8 weeks interventions, and then were tested in a step through passive avoidance learning and memory paradigm, to assess long term memory. Then serum levels of adiponectin, insulin and glucose were measured by ELISA and colorimetry respectively. Data were analyzed by Kruskal-Wallis, Mann-Whitney and also One-way analysis of variance (ANOVA). RESULTS: Eight weeks of HIIT and probiotic supplementation caused an increase in step through latency and shortening of total time spent in the dark compartment in OVX + Exe + Pro group compared with OVX + Veh group. Also significant increase in serum adiponectin levels, in parallel with a reduction in glucose, insulin and HOMA-IR were achieved by the group of OVX + Exe + Pro. CONCLUSION: The present study indicates that HIIT combined with probiotics supplementation for 8 weeks effectively improves associative memory in MetS model of rats partly via improving insulin sensitivity and adiponectin level.

Metabotropic Effect of Probiotic Supplementation and High-Intensity Interval Training in Menopause-Induced Metabolic Syndrome in Rats.

OBJECTIVES: This study aimed to investigate the interactive effect of supplementation with a native potential probiotic lactobacillus and 8-week high-intensity interval training (HIIT) on insulin resistance and dyslipidemia in a menopause-induced metabolic syndrome. METHODS: A total of 40 ovariectomized (OVX) Wistar rats were divided into five groups: control (OVX + Vehicle), exercise (EXE) (OVX + Exe), probiotic (Prob) (OVX + Prob), exercise and probiotic (OVX + Exe + Prob), and sham surgery. After the end of the treatment interventions, body weight, body mass index (BMI), waist circumference (WC), visceral fat, and serum concentrations of glucose, insulin, lipid profile, and adiponectin were measured using colorimetric analysis and enzyme-linked immunosorbent assay, respectively. RESULTS: Data revealed a significant decrease in weight, waist circumference , visceral fat, BMI, and levels of glucose, insulin, homeostasis model assessment of insulin resistance, triacylglyceride, total cholesterol, and low-density lipoprotein (LDL), but an increase in high-density lipoprotein and adiponectin levels (P = 0.001), in OVX + Exe + Prob compared with the OVX + Vehicle group. CONCLUSIONS: The present study indicates that native probiotic lactobacillus combined with HIIT effectively reduces body weight, visceral fat, and levels of LDL, glucose, and insulin and increases adiponectin level, although exercise contributes more to fat reduction and probiotics to insulin resistance.

Myocardial angiogenesis induced by concurrent vitamin D supplementation and aerobic-resistance training is mediated by inhibiting miRNA-15a, and miRNA-146a and upregulating VEGF/PI3K/eNOS signaling pathway.

This study aimed to investigate the effects of co-treatment of aerobic-resistance training (ART), vitamin D3 (VD3) on cardiovascular function considering the involvement of microRNA-15a and microRNA-146a, vascular endothelial growth factor (VEGF), phosphatidylinositol-3 kinase (PI3K), and endothelial nitric oxide synthase (eNOS) after myocardial infarction (MI) in rats. To induce MI, male Wistar rats subcutaneously received isoproterenol for 2 days, then MI was confirmed by echocardiography. MI rats were divided into six groups (n = 8/group). MI + VD3, MI + sesame oil (Veh), MI + ART, MI + VD3 + ART, and MI + Veh + ART, and received the related treatments for 8 weeks. Exercise tests, echocardiography, real-time quantitative polymerase chain reaction (qRT-PCR), western blotting, and histological staining were performed after the end of treatments. The highest ejection fraction (EF%), fractional shortening (FS%), exercise capacity (EC), and maximal load test (MLT) amounts were observed in the groups treated with VD3, ART, and VD3 + ART (P < 0.05). These were accompanied by a significantly increased angiogenesis post-MI. Furthermore, the levels of circulating microRNA-15a and microRNA-146a were significantly decreased in these groups compared to MI rats that were together with a significant upregulation of cardiac VEGF, PI3K, and eNOS expression. Overall, the best results were observed in the group treated with VD3 + ART. Concurrent VD3 supplementation and ART attenuated microRNA-15a and microRNA-146a and induced angiogenesis via VEGF/PI3K/eNOS axis. This data demonstrate that concurrent VD3 supplementation and ART is a more efficient strategy than monotherapy to improve cardiac function post-MI.

Protective effect of miR-34c antagomir against STZ-induced memory impairment by targeting mTOR and PSD-95 in the hippocampus of rats.

After long times of ongoing research, still there is no appropriate cure for Alzheimer's disease (AD). Recently, epigenetic alterations, particularly miRNA, have gotten attention in AD research. Among various miRNA, miR-34c has been addressed to be elevated in the brain of AD patients, however, its exact role and downstream mechanisms have not been elucidated yet. This study aimed to investigate the therapeutic potential of miR-34c antagomir on cognitive dysfunction induced by streptozocin (STZ), considering postsynaptic density protein 95 (PSD-95) and mammalian target of rapamycin expression (mTOR). Forty rats were cannulated intraventricularly under deep anesthesia using stereotaxic apparatus and divided into five groups: saline + saline, STZ + saline, STZ + miR-34c antagomir, STZ + lipofectamine, and STZ + scrambled, and received the related treatments for two weeks. At the end of the treatments, spatial memory and locomotor activity were assessed by Morris water maze (MWM), and open fields, respectively. Finally, PSD-95 and mTOR levels were measured by quantitative real-time PCR (qPCR) and western blotting on hippocampal samples. Results showed that miR-34c antagomir markedly ameliorated spatial learning and memory deficits induced by STZ, and significantly enhanced PSD-95 and mTOR levels in the hippocampus. In conclusion, miR-34c antagomir may be considered as a promising novel therapeutic target for AD patients.

Exercise training modulates adipokine dysregulations in metabolic syndrome.

Metabolic syndrome (MetS) is a cluster of risk factors for various metabolic diseases, and it is characterized by central obesity, dyslipidemia, hypertension, and insulin resistance. The core component for MetS is adipose tissue, which releases adipokines and influences physical health. Adipokines consist of pro and anti-inflammatory cytokines and contribute to various physiological functions. Generally, a sedentary lifestyle promotes fat accumulation and secretion of pro-inflammatory adipokines. However, regular exercise has been known to exert various beneficial effects on metabolic and cognitive disorders. Although the mechanisms underlying exercise beneficial effects in MetS are not fully understood, changes in energy expenditure, fat accumulation, circulatory level of myokines, and adipokines might be involved. This review article focuses on some of the selected adipokines in MetS, and their responses to exercise training considering possible mechanisms.

Effects of inhibiting astrocytes and BET/BRD4 chromatin reader on spatial memory and synaptic proteins in rats with Alzheimer's disease.

Communication between astrocytes and neurons has a profound effect on the pathophysiology of Alzheimer's disease (AD). Astrocytes regulate homeostasis and increase synaptic plasticity in physiological situations, however, they become activated during the progression of AD. Whether or not these reactions are supportive or detrimental for the central nervous system have not been understood yet. Considering epigenetic regulation of neuroinflammatory genes by chromatin readers, particularly bromodomain and extraterminal domain (BET) family, here we examined the effect of chronic co-inhibition of astrocytes metabolism (with fluorocitrate) and also BRD4 (with JQ1) on cognition deficit at early stages of AD. Forty adult male Wistar rats underwent stereotaxic cannulation for inducing AD by intrahippocampal injection of Aß1-42 (4 µg/8 µl/rat). Then animals were divided into five groups of Saline+DMSO, Aß + saline+DMSO, Aß + JQ1, Aß + FC (fluorocitrate), and Aß + JQ1 + FC and received the related treatments. Two weeks later, spatial memory was recorded by Morris Water Maze (MWM), and the levels of phosphorylated cyclic-AMP response element binding protein (CREB), postsynaptic density 95 (PSD95), synaptophysin (SYP), and tumor necrosis factor-alpha (TNF-α) were measured in the hippocampus by western blotting and RT-qPCR. Administration of JQ1 significantly improved both acquisition and retrieval of spatial memory, which were evident by decreased escape latency and increased total time spent (TTS) in target quadrant, and significant rise in p-CREB, PSD95, and synaptophysin compared with Aß + saline+DMSO group. In contrast, both groups receiving FC demonstrated memory decline, and reduction in p-CREB, PSD95 and synaptophysin in parallel with increase in TNF-α. Our data indicate that chronic inhibition of BRD4 significantly restores memory impaired by amyloid ß partly via CREB signaling and upregulating synaptic proteins of PSD95 and synaptophysin. However, inhibition of astrocytes nullifies the memory-boosting effects of JQ1 and reduces CREB/PSD95/synaptophysin levels in hippocampus.

Co-treatment of AMPA endocytosis inhibitor and GluN2B antagonist facilitate consolidation and retrieval of memory impaired by ß amyloid peptide.

BACKGROUND: Glutamate neurotransmission stands as an important issue to minimize memory impairment. We investigated the effects of an inhibitor of α-amino-3-hydroxy-5-methyl-4-isozazole propionic acid receptors (AMPA) endocytosis and GluN2B subunit of N-methyl-d-aspartate receptors (NMDA), either isolated or combined, on memory impairments induced by Amyloid beta1-42 (Aß). METHODS: Eighty male Wistar rats were used for two experiments of consolidation and retrieval of memory. Memory impairment was induced by intracerebroventricular (ICV) injection of Aß1-42 (2 µg/µl), and evaluated using Morris Water Maze (MWM). Each experiment consisted of 5 groups: Saline + Saline, Aß + Saline, Aß + Ifenprodil (Ifen, 3 nmol/ICV), Aß +Tat-GluR23Y (3 µmol/kg/IP), and Aß1 +Ifen + Tat-GluR23Y. Then, hippocampal cAMP-response element-binding protein (CREB) was measured by western blotting. Data were analyzed by Analysis of variance (ANOVA) repeated measure, and one-way Anova followed by Tukey's post hoc test. RESULTS: During retrieval, Aß+ Tat-GluR23Y showed significant improvement in total time spent (TTS) in the target quadrant (p = 0.009), escape latency to a platform (p = 0.008) and hippocampal level of CREB (p = 0.006) compared with Aß + saline. Also, coadministration of Tat-GluR23Yand Ifen similar to Tat-GluR23Y alone caused significant improvement in TTS (p = 0.014) and latency to platform (p = 0.013). During consolidation, shorter escape latency (p = 0.001), longer TTS (p = 0.002) and higher level of hippocampal CREB were observed in the Aß + Tat-GluR23Y (p = 0.001) and Aß+ Tat-GluR23Y + Ifen (p = 0.017), respectively. CONCLUSION: The present study provides pieces of evidence that inhibition of AMPARs endocytosis using Tat-GluR23Y facilitates memory consolidation and retrieval in Aß induced memory impairment via the CREB signaling pathway.

Simultaneous administration of bromodomain and histone deacetylase I inhibitors alleviates cognition deficit in Alzheimer's model of rats.

BACKGROUND: Histone deacetylases (HDACs) target various genes responsible for cognitive functions. However, chromatin readers, particularly bromodomain-containing protein 4 (BRD4), are capable to change the final products of genes. The objective of this study was to evaluate the simultaneous effects of inhibition of HDACs and BRD4 on spatial and aversive memories impaired by amyloid ß (Aß) in a rat model of Alzheimer's disease (AD) considering CREB and TNF-α signaling. METHODS: Forty male Wistar rats aged 3 months were randomly divided into five groups: saline +DMSO, Aß+saline+DMSO, Aß+JQ1, Aß+MS-275, Aß+JQ1+MS-275, and received the related treatments. MS-275, is the second generation of HDACs inhibitor, and JQ1 is a potent inhibitor of the BET family of bromodomain proteins in mammals. After the treatments, cognitive function was assessed by Morris water maze (MWM) and passive avoidance learning (PAL). The hippocampal level of mRNA for CREB and TNF-α, and also phosphorylated CREB were measured using real-time PCR and western blotting respectively. RESULTS: Administration of JQ1 and MS-275, either separately or simultaneously, improved acquisition and retrieval of spatial and aversive memories as it was evident by decreased escape latency and increased time spent in the target quadrant (TTS) in Morris water maze (MWM), together with increase in step-through latency, but reduced time spent in the dark zone time in passive avoidance learning (PAL) compared with Aß+saline+DMSO. Furthermore, there was a significant rise in the hippocampal level of CREB mRNA and phosphorylated CREB, but a reduction in TNF-α expression in comparison with Aß + Saline. CONCLUSION: Simultaneous administration of JQ1 and MS-275 improves acquisition and retrieval of both spatial and aversive memories partly via CREB and TNF-α signaling with no superiority to monotherapy.

NMDA and AMPA receptors dysregulation in Alzheimer's disease.

Alzheimer's disease (AD) is a progressive neurodegenerative condition characterized by cognitive dysfunction and synaptic failure. The current therapeutic approaches are mainly focused on symptomatic treatment and possess limited effectiveness in addressing the pathophysiology of AD. It is known that neurodegeneration is negatively correlated with synaptic plasticity. This negative correlation highlights glutamatergic neurotransmission via N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors and (AMPA) receptors as a critical mediator of synaptic plasticity. Despite this favorable role, extensive extracellular glutamate concentration induces excitotoxicity and neurodegeneration. NMDA receptors containing GluN2A subunits are located at synaptic sites, implicated in the protective pathways. In comparison, GluN2B containing receptors are located mainly at extrasynaptic sites and increase neuronal vulnerability. AMPA receptors are consistently endocytosed and recycled back to the membrane. An increase in the rate of endocytosis has been implicated as a part of AD pathophysiology through inducing long-term depression (LTD) and synaptic disintegration. In the present review, we focused on the mechanisms of glutamatergic system dysregulation in AD, particularly on its interaction with amyloid-beta. We concluded that assigning a specific role to an individual subtype of either NMDA receptors or AMPA receptors might be an oversimplification as they are not static receptors. Therefore, any imbalance between synaptic and extrasynaptic NMDA receptors and a reduced number of surface AMPA receptors will lead to synaptopathy.

Synergistic enhancing-memory effect of D-serine and RU360, a mitochondrial calcium uniporter blocker in rat model of Alzheimer's disease.

BACKGROUND: Although Amyloid beta (Aß) and N - methyl d- aspartate receptors (NMDARs are involved in Ca2+ neurotoxicity, the function of mitochondrial calcium uniporter in cognition deficit remain uncertain. Here, we examined the effect of mitochondrial calcium uniporter (MCU) blocker, together with NMDA receptor agonist d-cycloserine (DCS) on memory impairment in a rat model of AD. METHODS: Forty adult male Wistar rats underwent stereotaxic cannulation for inducing AD by intracerebroventricular (ICV) injection of Aß1-42 (5 µg /8 µl/rat). Then animals were divided into 5 groups of: Saline + Saline, Aß + Saline, Aß + RU360, Aß + DCS, Aß + RU360 + DCS. Two weeks after the treatments, Morris Water Maze (MWM) and step through passive avoidance learning (SPL) were undertaken for evaluating of spatial and associative memories, respectively. Hippocampal level of cyclic-AMP response element binding protein (CREB) and brain-derived neurotrophic factor (BDNF) were measured by western blot and ELISA. RESULTS: Co - administration of RU360 and DCS significantly improved both acquisition and retrieval of spatial memory as evident by decreased escape latency and increased time spent in the target quadrant (TTS) in MWM, together with increase in step-through latency, but reduced time spent in the dark compartment in SPL. Furthermore, there was a significant rise in the hippocampal level of CREB and BDNF in comparison with Aß + Saline. CONCLUSION: The present study supports the idea that co- administration of RU360 and DCS ameliorate memory impairment induced by Aß 1-42 probably via CREB / BDNF signaling.

Sex-Independent Cognition Improvement in Response to Kaempferol in the Model of Sporadic Alzheimer's Disease.

Alzheimer's disease (AD) is associated with neural oxidative stress and inflammation, and it is assumed to affect more women than men with unknown mechanisms. Kaempferol (KMP) as a potent natural antioxidant has been known to exhibit various biological and pharmacological functions, including antioxidant and anti-inflammatory. We aimed here to evaluate the role of gender difference in response to KMP on the rat model of sporadic AD. Forty-six female and male Wistar rats were divided into six groups of sham, streptozotocin (STZ) + saline (SAL), STZ + KMP. Female rats were ovariectomized, and then all animals received an intracerebroventricular bilateral injection of STZ (3 mg/kg) to induce the AD model. KMP (10 mg/kg) was intraperitoneally administered for 21 consecutive days. Afterward, spatial learning and memory were assessed via the Morris water maze task (MWM). Finally, the hippocampus level of superoxide dismutase (SOD), glutathione, and malondialdehyde were measured using calorimetric kits. Data showed a significant cognition deficit in STZ + SAL compared with the sham. To sum up, we reported that chronic KMP treatment increase significantly improved acquisition and retrieval of spatial memory as evident by longer TTS (total time spent) and short-latency to the platform in MWM. In addition, KMP increased the levels of SOD and glutathione in the hippocampus of rats. Also, KMP decreased hippocampal levels of malondialdehyde in both genders. In conclusion, KMP successfully restores spatial memory impairment independent of gender difference. This memory restoration may at least in part be mediated through boosting the hippocampal level of SOD and glutathione.

Acute effects of strength and endurance exercise on serum BDNF and IGF-1 levels in older men.

BACKGROUND: Regarding an important effects of physical exercise on brain function in elders, the aim of this study was to examine the effects of strength and endurance exercise on brain neurobiological factors in older men. METHODS: Thirty older men volunteered to participate in this study and were randomly assigned to strength, endurance and control groups. The subjects in strength group performed two circuits of resistance exercise (6 exercises with 10 repetition of 65-70% of one repetition maximum), while endurance group performed 30 min running with 65-70% of maximal heart rate. Blood was obtained pre and post-exercise to determine changes in serum BDNF, IGF-1 and platelets. RESULTS: After exercise, both the strength and endurance groups showed significant increases in serum BDNF and IGF-1 concentrations and platelets at post-exercise and in comparison to control group (p < 0.05). In addition, no statistically significant differences were detected between the strength and endurance groups at post-exercise. CONCLUSION: Our findings indicate that both the strength and endurance interventions are effective in elevating BDNF, IGF-1, and platelets, without significant differences between them.

Chronic administration of Tat-GluR23Y ameliorates cognitive dysfunction targeting CREB signaling in rats with amyloid beta neurotoxicity.

Alzheimer's disease (AD) is behaviorally characterized by memory impairments, and pathologically by amyloid ß1-42 (Aß1-42) plaques and tangles. Aß binds to excitatory synapses and disrupts their transmission due to dysregulation of the glutamate receptors. Here we hypothesized that chronic inhibition of the endocytosis of AMPA receptors together with GluN2B subunit of NMDA receptors might improve cognition deficit induced by Aß(1-42) neurotoxicity. Forty male Wistar rats were used in this study and divided into 5 groups: Saline + Saline, Aß+Saline, Aß+Ifen (Ifenprodil, 3 nmol /2 weeks), Aß+GluR23Y (Tat-GluR23Y 3 µmol/kg/2 weeks) and Aß+Ifen+GluR23Y (same doses and durations). Aß(1-42) neurotoxicity was induced by intracerebroventricular (ICV) injection of Aß1-42 (2 µg/µl/side), and then animals received the related treatments for 14 days. Cognitive performance of rats and hippocampal level of cAMP-response element-binding (CREB) were evaluated using Morris Water Maze (MWM), and western blotting respectively. Obtained data from the acquisition trials were analyzed by two way Anova and Student T test. Also one way Analysis of variance (ANOVA) with post hoc Tuckey were used to clarify between groups differences in probe test. The Group receiving Aß, showed significant cognition deficit (long latency to platform and short total time spent in target quadrant (TTS), parallel with lower level of hippocampal CREB, versus vehicle group. While, Aß+ GluR23Y exhibited the shortest latency to platform and the longest TTS during the probe test, parallel with the higher hippocampal level of CREB compared with other groups. The present study provides evidence that chronic administration of Tat-GluR23Y; an inhibitor of GluA2-AMPARs endocytosis, successfully restores spatial memory impaired by amyloid beta neurotoxicity targeting CREB signaling pathway.

Concurrent vitamin D supplementation and exercise training improve cardiac fibrosis via TGF-ß/Smad signaling in myocardial infarction model of rats.

Although the role of vitamin D in various types of disorders such as cancer and diabetes has been well recognized, its relation to cardiovascular diseases still remains equivocal. The present study aims to investigate the interactive effects of aerobic-resistance training (ART) and vitamin D3 (VD3) on both cardiac fibrosis and heart functions considering TGF-ß1/Smad2, 3 (transforming growth factor-ß1/mothers against decapentaplegic homolog 2/3) signaling in the myocardial infarction (MI) model of rats. Fifty-six male Wistar rats were divided into 2 groups of sham (n = 8), and MI (n = 48). Then, MI rats were divided into six groups of VD3, ART, VD3+ART, Veh, Veh+ART, and sedentary MI. The animals received the related treatments for 8 weeks, and then their functional exercise capacity (FEC) and strength gain (SG) were estimated through exercise tests. Ejection fraction (EF%) and fractional shortening (FS%) and serum level of VD3 were measured by echocardiography and ELISA, respectively. Cardiac expressions of TGF-ß1, Smad2/3, and collagen I/III were assessed by western blotting and fibrosis by Masson's trichrome staining. The highest EF, parallel with the lowest expression of cardiac TGF-ß1, Smad2/3, collagen I, and collagen III were observed in MI + VD3 (P = 0.021), MI + ART (P = 0.001), and MI + VD3 + ART (P < 0.001). Furthermore, similar to FS, the highest FEC and SG were related to the groups of MI + VD3 + ART and MI + ART compared to the MI group. In conclusion, our data indicate that concurrent vitamin D supplementation and ART, compared with monotherapy, successfully improve cardiac function and alleviate myocardial fibrosis via downregulating TGF-ß1, Smad2/3 signaling, and also regulating collagen I and III expressions.

Exercise Training Improves Memory Performance in Older Adults: A Narrative Review of Evidence and Possible Mechanisms.

As human life expectancy increases, cognitive decline and memory impairment threaten independence and quality of life. Therefore, finding prevention and treatment strategies for memory impairment is an important health concern. Moreover, a better understanding of the mechanisms involved underlying memory preservation will enable the development of appropriate pharmaceuticals drugs for those who are activity limited. Exercise training as a non-pharmacological tool, has been known to increase the mean lifespan by maintaining general body health and improving the cardiovascular and nervous systems function. Among different exercise training protocols, aerobic exercise has been reported to prevent the progression of memory decline, provided adequate exertion level, duration, and frequency. Mechanisms underlying exercise training effects on memory performance have not been understood yet. Convergent evidence suggest several direct and indirect mechanisms at molecular and supramolecular levels. The supramolecular level includes improvement in blood circulation, synaptic plasticity and neurogenesis which are under controls of complex molecular signaling of neurotransmitters, neurotrophic factors, exerkines, and epigenetics factors. Among these various factors, irisin/BDNF signaling seems to be one of the important mediators of crosstalk between contracted skeletal muscles and the brain during exercise training. This review provides an affordable and effective method to improve cognitive function in old ages, particularly those who are most vulnerable to neurodegenerative disorders.

The methanolic extract of Cinnamomum zeylanicum bark improves formaldehyde-induced neurotoxicity through reduction of phospho-tau (Thr231), inflammation, and apoptosis.

Accumulation of formaldehyde (FA) in the brain is linked to age-related neurodegenerative disorders, as it accelerates memory impairment through tau protein aggregation, inflammation, and nuclear damage. This study aimed to assess the possible effects of methanolic cinnamon extract (CE) on FA-induced neurotoxicity in rats. The animals were treated with CE (100, 200, and 400 mg/kg, P.O.) for 30 days following FA administration (60 mg/kg, I.P.) for 30 days. Briefly, spatial and inhibitory memory were examined by Morris water maze (MWM) and passive avoidance (PA) tasks, respectively. The Nissl, Hoechst, and Bielschowsky silver staining methods were also used to assess apoptosis and neurofibrillary tangles (NFTs) in the hippocampal CA1 region, respectively. Brain tissues were probed with an anti-phospho-tau (Thr231) monoclonal antibody to assess tau hyperphosphorylation. Inflammatory cytokines (IL-1ß, IL-6, and TNF-α) were also measured by ELISA assay. Western blotting was performed to quantify the amount of phospho-tau (Thr231), caspase-8, and caspase-9. The results showed that FA injection significantly caused tau hyperphosphorylation at Thr231 residue, which in turn disturbed the MWM performance. The ratio of apoptotic to intact neurons increased following FA treatment. The results of Western blotting indicated that the hippocampal levels of phospho-tau (Thr231) and caspase-8 were significantly higher in the FA group compared to the control group. The hippocampal levels of IL-1ß, IL-6, and TNF-α in the FA group were also higher than the control group. Administration of 200 mg/kg of CE significantly improved the rats' MWM performance, decreased the levels of phospho-tau (Thr231), caspase-8, IL-6, and TNF-α, and reduced the ratio of apoptotic to intact neurons. Overall, cinnamon improved cognitive performance in FA-treated rats by eliminating tau hyperphosphorylation, inflammatory cytokines, and nuclear damage.