Effects of (S)-3,4-DCPG, an mGlu8 receptor agonist, on hippocampal long-term potentiation at perforant pathway-dentate gyrus synapses in prenatal valproic acid-induced rat model of autism.

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

Effect of intrahippocampal microinjection of VU0155041, a positive allosteric modulator of mGluR4, on long term potentiation in a valproic acid-induced autistic male rat model.

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

S-3,4-DCPG, a potent orthosteric agonist for the mGlu8 receptor, facilitates extinction and inhibits the reinstatement of morphine-induced conditioned place preference in male rats.

The limbic system, particularly the NAc, shows a high concentration of metabotropic glutamate receptors (mGluRs). Recent evidence suggests the significant involvement of mGluRs in mental disorders, including substance abuse and addiction. The objective of this study was to examine the involvement of mGlu8 receptors in the NAc in the mechanisms underlying the extinction and reinstatement of conditioned place preference (CPP) induced by morphine. Male Wistar rats underwent surgical implantation of bilateral cannulas in the NAc and were assessed in a CPP protocol. In study 1 at the same time as the extinction phase, the rats were given varying doses of S-3,4-DCPG (0.03, 0.3, and 3 µg/0.5 µl). In study 2, rats that had undergone CPP extinction were given S-3,4-DCPG (0.03, 0.3, and 3 µg/0.5 µl) five minutes prior to receiving a subthreshold dose of morphine (1 mg/kg) in order to reactivate the previously extinguished morphine response. The findings demonstrated that administering S-3,4-DCPG directly into the accumbens nucleus resulted in a decrease in the duration of the CPP extinction phase. Moreover, dose-dependent administration of S-3,4-DCPG into the NAc inhibited CPP reinstatement. The observations imply that microinjection of S-3,4-DCPG as a potent orthosteric agonist with high selectivity for the mGlu8 receptor into the NAc promotes the process of extinction while concurrently exerting inhibitory effects on the reinstatement of morphine-induced CPP. This effect may be associated with the modulation of glutamate engagement within the NAc and the plasticity of reward pathways at the synaptic level.

Vitamin D Protects Against Cardiac Hypertrophy Through the Regulation of Mitochondrial Function in Aging Rats.

Cardiac aging is defined as mitochondrial dysfunction of the heart. Vitamin D (VitD) is an effective agent in ameliorating cardiovascular disorders. In this study, we indicated the protective effects of VitD against cardiac aging. Male Wistar rats were randomly divided into four groups: control (CONT), D-galactose (D-GAL): aged rats induced by D-GAL, D-GAL + Ethanol: aged rats treated with ethanol, and D-GAL + VitD aged rats treated with VitD. Aging was induced by D-GAL at 150 mg/kg via intraperitoneal injection for 8 weeks. Aged rats were treated with VitD (D-GAL + VitD) by gavage for 8 weeks. The serum samples were used to evaluate biochemical factors, and heart tissues were assessed to determine oxidative stress and gene expression. The D-GAL rats exhibited cardiac hypertrophy, which was associated with decreased antioxidant enzyme activity, enhanced oxidative marker, and changes in the expression of mitochondrial genes in comparison with the control rats. Co-treatment with VitD ameliorated all these changes. In conclusion, VitD could protect the heart against D-GAL-induced aging via enhancing antioxidant effects, and the expression of mitochondrial genes.

Underlying mechanisms behind the neuroprotective effect of vanillic acid against diabetes-associated cognitive decline: An in vivo study in a rat model.

Hippocampal synaptic dysfunction, oxidative stress, neuroinflammation, and neuronal loss play critical roles in the pathophysiology of diabetes-associated cognitive decline (DACD). The study aimed to investigate the effects of vanillic acid (VA), a phenolic compound, against DACD and explore the potential underlying mechanisms. Following confirmation of diabetes, rats were treated with VA (50 mg/kg/day; P.O.) or insulin (6 IU/rat/day; S.C.) for 8 consecutive weeks. The cognitive performance of the rats was evaluated using passive-avoidance and water-maze tasks. Long-term potentiation (LTP) was induced at hippocampal dentate gyrus (DG) synapses in response to high-frequency stimulation (HFS) applied to the perforant pathway (PP) to evaluate synaptic plasticity. Oxidative stress factors, inflammatory markers, and histological changes were evaluated in the rat hippocampus. This study showed that streptozotocin (STZ)-induced diabetes caused cognitive decline that was associated with inhibition of LTP induction, suppression of enzymatic antioxidant activities, enhanced lipid peroxidation, elevated levels of inflammatory proteins, and neuronal loss. Interestingly, chronic treatment with VA alleviated blood glucose levels, improved cognitive decline, ameliorated LTP impairment, modulated oxidative-antioxidative status, inhibited inflammatory response, and prevented neuronal loss in diabetic rats at a level comparable to insulin therapy. The results suggest that the antihyperglycemic, antioxidative, anti-inflammatory, and neuroplastic properties of VA may be the mechanisms behind its neuroprotective effect against DACD.

Comparison of the preconditioning effect of different exercise training modalities on myocardial ischemia-reperfusion injury.

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

Effect of vitamin D on cardiac hypertrophy in D-galactose-induced aging model through cardiac mitophagy.

BACKGROUND: Cardiac apoptosis plays a key role in increased morbidity associated with aging-induced-cardiac disorder. Mitochondria play an important role in cardiac apoptosis, and dynamin-related protein 1 (Drp1), as a main mediator of mitochondrial fission, can trigger the mitophagy process to sustain the mitochondrial quality. The present study was done to determine the effect of vitamin D (VitD) treatment on cardiac hypertrophy through mitophagy regulation in aged animals induced by D-galactose (D-GAL). METHODS AND RESULTS: Male Wistar rats were randomly divided into four groups: control, D-GAL (aging group), D-GAL co-injected with VitD (D-GAL ± VitD), and D-GAL plus ethanol (D-GAL ± Ethanol). Aging was induced by an intraperitoneal (i.p.) administration of D-GAL at 150 mg/kg daily for eight weeks and also VitD (400 IU/kg) or ethanol was injected (i.p.) into aging rats. Then, the levels of cardiac mitophagy and cardiac apoptosis were determined by measuring the expression of tensin homologue (PTEN)-induced putative kinase 1 (PINK1), Drp1, Bcl2-Associated X (Bax), and B-cell lymphoma 2 (Bcl2) genes. Aging in rats was associated with a reduction in mitophagy and also an increase in apoptosis of the heart through down-regulation of Drp1, PINK1, and Bcl2 genes and also up-regulation of Bax. However, VitD improved cardiac hypertrophy through cardiac mitophagy in D-GAL-induced aging rats. CONCLUSION: VitD can inhibit cardiac hypertrophy by an increase in mitophagy and a decrease in apoptosis in the aging heart. The illustration of the suggested mechanism underlying of Vitamin D in cardiac hypertrophy induced by aging.

Maternal high-intensity interval training as a suitable approach for offspring's heart protection in rat: evidence from oxidative stress and mitochondrial genes.

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

Geraniol improves passive avoidance memory and hippocampal synaptic plasticity deficits in a rat model of Alzheimer's disease.

Alzheimer's disease (AD) is the most progressive and irreversible neurodegenerative disease that leads to synaptic loss and cognitive decline. The present study was designed to evaluate the effects of geraniol (GR), a valuable acyclic monoterpene alcohol, with protective and therapeutic effects, on passive avoidance memory, hippocampal synaptic plasticity, and amyloid-beta (Aß) plaques formation in an AD rat model induced by intracerebroventricular (ICV) microinjection of Aß1-40. Seventy male Wistar rats were randomly into sham, control, control-GR (100 mg/kg; P.O. (orally), AD, GR-AD (100 mg/kg; P.O.; pretreatment), AD-GR (100 mg/kg; P.O.; treatment), and GR-AD-GR (100 mg/kg; P.O.; pretreatment & treatment). Administration of GR was continued for four consecutive weeks. Training for the passive avoidance test was carried out on the 36th day and a memory retention test was performed 24 h later. On day 38, hippocampal synaptic plasticity (long-term potentiation; LTP) was recorded in perforant path-dentate gyrus (PP-DG) synapses to assess field excitatory postsynaptic potentials (fEPSPs) slope and population spike (PS) amplitude. Subsequently, Aß plaques were identified in the hippocampus by Congo red staining. The results showed that Aß microinjection increased passive avoidance memory impairment, suppressed of hippocampal LTP induction, and enhanced of Aß plaque formation in the hippocampus. Interestingly, oral administration of GR improved passive avoidance memory deficit, ameliorated hippocampal LTP impairment, and reduced Aß plaque accumulation in the Aß-infused rats. The results suggest that GR mitigates Aß-induced passive avoidance memory impairment, possibly through alleviation of hippocampal synaptic dysfunction and inhibition of Aß plaque formation.

Regulatory effects of trimetazidine in cardiac ischemia/reperfusion injury.

Ischemia/reperfusion (I/R) injury is a tissue damage during reperfusion after an ischemic condition. I/R injury is induced by pathological cases including stroke, myocardial infarction, circulatory arrest, sickle cell disease, acute kidney injury, trauma, and sleep apnea. It can lead to increased morbidity and mortality in the context of these processes. Mitochondrial dysfunction is one of the hallmarks of I/R insult, which is induced via reactive oxygen species (ROS) production, apoptosis, and autophagy. MicroRNAs (miRNAs, miRs) are non-coding RNAs that play a main regulatory role in gene expression. Recently, there are evidence, which miRNAs are the major modulators of cardiovascular diseases, especially myocardial I/R injury. Cardiovascular miRNAs, specifically miR-21, and probably miR-24 and miR-126 have protective effects on myocardial I/R injury. Trimetazidine (TMZ) is a new class of metabolic agents with an anti-ischemic activity. It has beneficial effects on chronic stable angina by suppressing mitochondrial permeability transition pore (mPTP) opening. The present review study addressed the different mechanistic effects of TMZ on cardiac I/R injury. Online databases including Scopus, PubMed, Web of Science, and Cochrane library were assessed for published studies between 1986 and 2021. TMZ, an antioxidant and metabolic agent, prevents the cardiac reperfusion injury by regulating AMP-activated protein kinase (AMPK), cystathionine-γ-lyase enzyme (CSE)/hydrogen sulfide (H2S), and miR-21. Therefore, TMZ protects the heart against I/R injury by inducing key regulators such as AMPK, CSE/H2S, and miR-21.

Neuroprotective effects of vinpocetine, as a phosphodiesterase 1 inhibitor, on long-term potentiation in a rat model of Alzheimer's disease.

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

Effects of sesamin on Aß1-42-induced oxidative stress and LTP impairment in a rat model of Alzheimer's disease.

The present study examined the protective effect of sesamin (Ses) on ß-amyloid (Aß)-induced long-term potentiation (LTP) impairment at the PP-DG synapses in male rats. Wistar rats were randomly assigned to seven groups: control, sham, Aß; ICV Aß1-42 microinjection, Ses, Aß + Ses; first, ICV Aß injections and then receiving Ses, Ses + Aß: four weeks of pretreatment with Ses and then Aß injection, and Ses + Aß + Ses: pre (four weeks) and post (four weeks) treatment with Ses. Ses-treated groups received 30 mg/kg of Ses once a day by oral gavage for four weeks. After the treatment period, the animals were positioned in a stereotaxic device for surgery and field potential recording. The population spike (PS) amplitude and slope of excitatory postsynaptic potentials (EPSP) were evaluated in the DG region. Serum oxidative stress biomarkers (total oxidant status (TOS) and total antioxidant capacity (TAC)) were measured. Aß impaired LTP induction at the PP-DG synapses evidenced by a decrease in EPSP slope and PS amplitude of LTP. In Aß rats, Ses increased EPSP slope and PS amplitude of LTP in the DG granular cells. Also, an increase in TOS and a reduction in TAC caused by Aß were significantly corrected by Ses. Ses could prevent Aß-induced LTP impairment at the PP-DG synapses in male rats, which can be due to its preventive effects on oxidative stress.

Possible mechanisms involved in the protective effects of chrysin against lead-induced cognitive decline: An in vivo study in a rat model.

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

p-Coumaric acid ameliorates cognitive and non-cognitive disturbances in a rat model of Alzheimer's disease: The role of oxidative stress and inflammation.

BACKGROUND: Alzheimer's disease (AD) is the most progressive form of neurodegenerative disease resulting in cognitive and non-cognitive deficits. Aluminum is recognized as a risk factor for the etiology, pathogenesis, and progression of AD. The present study was designed to determine the effects of p-coumaric acid (p-CA), a phenolic compound, on spatial cognitive ability and non-cognitive functions and to identify the role of oxidative stress and inflammation in an AD rat model induced by aluminum chloride (AlCl3). METHODS: Both AlCl3 (100 mg/kg/day; P.O.) and p-CA (100 mg/kg/day; P.O.) treatments were given for six consecutive weeks. During the fifth and sixth weeks of the treatment period, the cognitive and non-cognitive functions of the rats were assessed using standard behavioral tests. Additionally, oxidative-antioxidative status, inflammatory markers, and histological changes were evaluated in the cerebral cortex and hippocampal regions of the rats. RESULTS: The results of this study showed that AlCl3 exposure enhanced anxiety-/depression-like behaviors, reduced locomotor/exploratory activities, and impaired spatial learning and memory. These cognitive and non-cognitive disturbances were accompanied by increasing oxidative stress, enhancing inflammatory response, and neuronal loss in the studied brain regions. Interestingly, treatment with p-CA alleviated all the above-mentioned neuropathological changes in the AlCl3-induced AD rat model. CONCLUSION: The findings suggest that both anti-oxidative and anti-inflammatory properties of p-CA may be the underlying mechanisms behind its beneficial effect in preventing neuronal loss and improving cognitive and non-cognitive deficits associated with AD.

Interval training and Crataegus persica ameliorate diabetic nephropathy via miR-126/Nrf-2 mediated inhibition of stress oxidative in rats with diabetes after myocardial ischemia-reperfusion injury.

Myocardial disorders are the most common cause of renal failure and mortality in diabetic patients, but the molecular mechanism of this process is not yet clear. The reduction of nuclear Erythroid2-related factor-2 (Nrf-2) and positive regulators of Nrf-2 proteins, such as DJ-1 and microRNA-126 (miR-126), after hypoxia and the promotion of reactive oxygen species, might be an intervention indicator in renal failure after myocardial ischemia-reperfusion. Therefore, this study evaluates the renoprotective effect of exercise training and Crataegus persica extract (CE) on myocardial ischemia-reperfusion-induced kidney injury in diabetic rats. Fifty rats were divided into five groups: healthy sedentary control (Con), sedentary diabetic (D), interval trained diabetic (TD), diabetic plus Crataegus persica extract treatment (CD), and interval trained diabetic plus Crataegus persica extract treatment (TCD) groups. The rats in the exercise groups were subjected to moderate-intensity interval training five days per week for ten weeks. The rats in CD and TCD groups received 300 mg/kg of Crataegus persica through gavage for ten weeks. Then, the subjects underwent 30 min of myocardial ischemia and subsequently reperfusion for 24 h. At the end of the experiment, insulin sensitivity, oxidative stress, renal function, histopathology of the kidney, Nrf-2, miR-126, and DJ-1 gene expression levels were evaluated. The results show that the treatments decreased elevated levels of renal oxidative stress, glomerular filtration rate, insulin sensitivity, and pathological score in diabetic rats. Also, the expression of Nrf-2 and miR-126, unlike DJ-1, decreased in diabetic rats due to interval training. Due to the results, diabetes aggravates acute myocardial ischemia-reperfusion-induced kidney injury, while moderate-intensity interval training and Crataegus persica treatment simultaneously ameliorate myocardial ischemia-reperfusion-induced renal injury via miR-126/Nrf-2 pathway and improve insulin sensitivity and renal function in type 1 diabetic rats.

Impairment in social interaction and hippocampal long-term potentiation at perforant pathway-dentate gyrus synapses in a prenatal valproic acid-induced rat model of autism.

It is well established that prenatal valproic acid exposure in rats leads to autism-like behaviours and social deficits. Long-term potentiation changes in the brain have been proposed as a potential mechanism in the development of autistic behaviour. However, there are controversies regarding the effect of in utero valproic acid exposure on long-term potentiation. This study examined the social interaction and long-term potentiation induction in perforant pathway-dentate gyrus synapses in male offspring of a rat model of autism induced by prenatal exposure to valproic acid. On Embryonic Day 12.5, the pregnant dams received an injection of 500 mg/kg valproic acid (intraperitoneal) to produce the autism model. The sociability test was performed between Postnatal Days 37 and 40. The offsprings were urethane-anaesthetized and placed into a stereotaxic apparatus for surgery, electrode implantation and field potential recording on Postnatal Days 45-55. In the dentate gyrus region, excitatory postsynaptic potential slope and population spike amplitude were measured. Valproic acid-exposed offspring showed significantly impaired social interaction. The birth weight in valproic acid-exposed rats was significantly lower than in control rats. The ability of dentate gyrus synapses to induce long-term potentiation was hampered by valproic acid exposure. The decreasing excitatory postsynaptic potential slope and population spike amplitude of long-term potentiation provide evidence in favour of this notion. It is widely supposed that the hippocampus plays a central role in the process of learning and memory as well as social interaction and social memory. Therefore, deficiencies in hippocampal synaptic plasticity may be responsible, at least in part, for the social interaction deficits in valproic acid-exposed rats.

Neuroprotective effect of geraniol on neurological disorders: a review article.

BACKGROUND: Neurological disorders are structural, biochemical, and electrical abnormalities that affect the peripheral and central nervous systems. Paralysis, muscle weakness, tremors, spasms, and partial or complete loss of sensation are some symptoms of these disorders. Neurorehabilitation is the main treatment for neurological disorders. Treatments can improve the quality of life of patients. Neuroprotective substances of natural origin are used for the treatments of these disorders. METHODS AND RESULTS: Online databases, such as Google Scholar, PubMed, ScienceDirect, and Scopus were searched to evaluate articles from 1981-2021 using the Mesh words of geraniol (GER), neurological disorders, epilepsy, spinal cord injury (SCI), Parkinson's diseases (PD), and depression. A total of 87 studies were included in this review. GER with antioxidant, anti-inflammatory, and neuroprotective effects can improve the symptoms and reduce the progression of neurological diseases. GER exhibits neuroprotective effects by binding to GABA and glycine receptors as well as by inhibiting the activation of nuclear factor kappa B (NF-κB) pathway and regulating the expression of nucleotide-binding oligomerization of NLRP3 inflammasome. In this study, the effect of GER was investigated on neurological disorders, such as epilepsy, SCI, PD, and depression. CONCLUSION: Although the medicinal uses of GER have been reported, more clinical and experimental studies are needed to investigate the effect of using traditional medicine on improving lifethreatening diseases and the quality of life of patients.

Sex Differences in Spatial Learning and Memory in Valproic Acid Rat Model of Autism: Possible Beneficial Role of Exercise Interventions.

In the current study, we first tried to determine sex differences in spatial learning and memory in the valproic acid (VPA) rat model of autism. Second, the effects of interval training (IT) and continuous training (CT) exercises were examined in male and female offsprings. To induce autism-like animal model, the pregnant rats were injected 500 mg/kg NaVPA (intraperitoneal) at the embryonic day 12.5. IT and CT aerobic exercises were started at postnatal day 56. Then, on postnatal days 84-89, a Morris water maze (MWM) test was conducted on the separate groups of offsprings. Aerobic training was performed on a rodent treadmill with 0% slope for 8 weeks, 5 days/week, and 50 min/day. Unlike control animals, VPA-exposed female offspring had a better performance than VPA-exposed male offspring in MWM acquisition. In the case of MWM reference memory, we did not observe a sex difference between VPA-exposed male and VPA-exposed female offspring. Both IT and CT exercises in both control and VPA-exposed male rats significantly improved MWM acquisition. Moreover, both IT and CT exercises significantly improved MWM acquisition in control female rats. In addition, IT exercise (but not CT) significantly improved MWM acquisition in VPA-exposed female offsprings. Both IT and CT exercises in VPA-exposed that male and female offsprings improved the MWM reference memory. In conclusion, our observation demonstrated that prenatal exposure to VPA affects the spatial learning and memory in a sex dependent manner. We have shown that both IT and CT exercises are able to improve cognitive function in healthy and autistic rat offsprings.

The effect of different exercise training modes on dentate gyrus neurodegeneration and synaptic plasticity in morphine-dependent rats.

Various impacts of exercise on brain performance following the induction of morphine dependence have been documented; however, the underlying neuronal mechanisms are still unclear. The present research was done to investigate the impact of different exercise training modes on apoptosis, neuronal maturation, and synaptic plasticity in the perforant pathway (PP)-dentate gyrus (DG) synapses in the morphine-dependent rats. Five groups, including a control group (Con, ten healthy rats) and forty morphine-dependent rats were considered as follows (n = 10/group): 1) sedentary-dependent (Sed-D); 2) endurance exercise-dependent (En-D); 3) strength exercise-dependent (St-D); and 4) concurrent exercise-dependent (Co-D). The exercise training groups were subjected to endurance, strength, and concurrent training five days a week for ten weeks. After training sessions, the field excitatory postsynaptic potential (fEPSP) slope and population spike (PS) amplitude in the DG were determined in response to high-frequency stimulation (HFS) of the PP. For assessing neurogenesis and apoptosis, NeuroD and Caspase-3 expression levels were evaluated after all experiments. Concurrent training increased PS amplitude and EPSP compared to the control group. NeuroD in the morphine-dependent rats significantly decreased, but concurrent training returned the NeuroD to its levels in healthy rats. Furthermore, Caspase-3 expression levels in morphine-dependent rats remarkably increased and concurrent training significantly reduced Caspase-3 expression levels compared to the Sed-D group. Concurrent training can ameliorate synaptic plasticity impairment in morphine-dependent rats through neurogenesis promotion and apoptosis reduction. According to the results, concurrent training can be an appropriate novel candidate for treating opioid addiction.