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.

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.

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.

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.

Sex differences in spatial learning and memory and hippocampal long-term potentiation at perforant pathway-dentate gyrus (PP-DG) synapses in Wistar rats.

BACKGROUND: Recent studies show that gender may have a significant impact on brain functions. However, the reports of sex effects on spatial ability and synaptic plasticity in rodents are divergent and controversial. Here spatial learning and memory was measured in male and female rats by using Morris water maze (MWM) task. Moreover, to assess sex difference in hippocampal synaptic plasticity we examined hippocampal long-term potentiation (LTP) at perforant pathway-dentate gyrus (PP-DG) synapses. RESULTS: In MWM task, male rats outperformed female rats, as they had significantly shorter swim distance and escape latency to find the hidden platform during training days. During spatial reference memory test, female rats spent less time and traveled less distance in the target zone. Male rats also had larger LTP at PP-DG synapses, which was evident in the high magnitude of population spike (PS) potentiation and the field excitatory post synaptic potentials (fEPSP) slope. CONCLUSIONS: Taken together, our results suggest that sex differences in the LTP at PP-DG synapses, possibly contribute to the observed sex difference in spatial learning and memory.

Exercise training and probiotic supplementation effects on skeletal muscle apoptosis prevention in type-Ι diabetic rats.

AIMS: Hyperglycemia occurring in the diabetic condition can cause apoptosis via the mitochondrial pathway with higher pro-apoptotic protein expression. Probiotics are viable microorganisms that have anti-diabetic and antioxidant effects. Also, exercise may affect the signaling pathways of skeletal muscle apoptosis. This study examined the aerobic exercise training and probiotic supplementation effects on some apoptotic indices of the soleus muscle in diabetic rats-induced by streptozotocin. MAIN METHODS: We examined 32 male Wistar rats (weight: 250-270 g; age: eight weeks old) and divided them into four groups: control, control + probiotics, aerobic training (AT), and AT + probiotics (ATS). The rats in the training groups aerobically exercised using a treadmill five days per week for five weeks. We evaluated the gene expression of Bax, Bcl2, and p53 using the RT-PCR. We also used a one-way ANOVA for statistical analysis and set the significance level at P ≤ 0.05. KEY FINDINGS: The results showed that the fasting blood sugar was significantly higher in the control and control + probiotics groups (P = 0.008). Moreover, the AT + probiotics group showed lower expression of p53 (P = 0.005), Bax (P = 0.001) and the Bax/Bcl2 ratio (P = 0.001). Conversely, Bcl2 expression was higher after aerobic training and receiving probiotics (P = 0.002). However, the groups revealed no significant difference regarding muscle weight (P = 0.053) and the muscle weight/final body weight ratio of the rats (P = 0.26). SIGNIFICANCE: It appears that aerobic exercise training with the use of probiotics prevents apoptosis in the muscle with the down-regulation of blood glucose.

Evidence of Improved Vascular Function in the Arteries of Trained but Not Untrained Limbs After Isolated Knee-Extension Training.

Vascular endothelial function is a strong marker of cardiovascular health and it refers to the ability of the body to maintain the homeostasis of vascular tone. The endothelial cells react to mechanical and chemical stimuli modulating the smooth muscle cells relaxation. The extent of the induced vasodilation depends on the magnitude of the stimulus. During exercise, the peripheral circulation is mostly controlled by the endothelial cells response that increases the peripheral blood flow in body districts involved but also not involved with exercise. However, whether vascular adaptations occur also in the brachial artery as a result of isolated leg extension muscles (KE) training is still an open question. Repetitive changes in blood flow occurring during exercise may act as vascular training for vessels supplying the active muscle bed as well as for the vessels of body districts not directly involved with exercise. This study sought to evaluate whether small muscle mass (KE) training would induce improvements in endothelial function not only in the vasculature of the lower limb (measured at the femoral artery level in the limb directly involved with training), but also in the upper limb (measured at the brachial artery level in the limb not directly involved with training) as an effect of repetitive increments in the peripheral blood flow during training sessions. Ten young healthy participants (five females, and five males; age: 23 ± 3 years; stature: 1.70 ± 0.11 m; body mass: 66 ± 11 kg; BMI: 23 ± 1 kg ⋅ m-2) underwent an 8-week KE training study. Maximum work rate (MWR), vascular function and peripheral blood flow were assessed pre- and post-KE training by KE ergometer, flow mediated dilatation (FMD) in the brachial artery (non-trained limb), and by passive limb movement (PLM) in femoral artery (trained limb), respectively. After 8 weeks of KE training, MWR and PLM increased by 44% (p = 0.015) and 153% (p = 0.003), respectively. Despite acute increase in brachial artery blood flow during exercise occurred (+25%; p < 0.001), endothelial function did not change after training. Eight weeks of KE training improved endothelial cells response only in the lower limb (measured at the femoral artery level) directly involved with training, likely without affecting the endothelial response of the upper limb (measured at the brachial artery level) not involved with training.

Mitochondrial dynamics as an underlying mechanism involved in aerobic exercise training-induced cardioprotection against ischemia-reperfusion injury.

AIMS: Ischemia-reperfusion injury is one of the most common cardiac disorders leading to irreversible heart damage. Many underlying mechanisms seem to be involved, among which mitochondrial dysfunction. Since physical training has a beneficial effect on mitochondrial dynamics (fusion and fission), it may have a cardioprotective effect against IR injury also via mitochondrial pathways. This study investigates the protective role of aerobic training against cardiac IR injury and the mitochondrial dynamics as a possible mechanism. MAIN METHODS: Thirty-two male Wistar rats (8-week old) were divided into a control, sham, control + IR, and training + IR groups (8 rats each). Training group was exercised aerobically on a treadmill for 8 weeks (5 days/week). After 8 weeks, anesthetized rats underwent a left thoracotomy (sham, control + IR, and training + IR groups) to access the left anterior descending coronary artery, which was occluded by a silk suture for 30 min and released for 90 min of reperfusion (IR groups). Triphenyltetrazolium chloride staining was used to determine the infarct size. The gene expression of mitofusin 1 (Mfn1), mitofusin 2 (Mfn2), and dynamin-related protein 1 (Drp1) was evaluated by RT-PCR. A one-way ANOVA was used for statistical analysis with the significance level set at P ≤ 0.05. KEY FINDINGS: Cardiac infarct size was smaller In training + IR group (20.24 ±â€¯5.7%) than in control + IR (35.9 ±â€¯2.3%; P ≤ 0.05). Training + IR showed higher expression of Mfn1 and Mfn2 (P ≤ 0.05). Conversely, Drp1 expression was lower after training (P ≤ 0.05). SIGNIFICANCE: Exercise-induced regulation of mitochondrial fusion and fission, leading to improvement of mitochondrial dynamics seems to be involved in the cardioprotection against IR injuries.

Evaluation of the prevalence of waterpipe tobacco smoking and its related factors in Tehran, Islamic Republic of Iran.

This study is designed to evaluate the prevalence of waterpipe tobacco smoking and its related factors among Iranian adults. This is a cross-sectional study carried out during 2013/14 in Tehran, Islamic Republic of Iran, among 1830 citizens aged over 15 years. Sampling was through Stratified multistage cluster sampling with proportional allocation within strata. Global Adult Tobacco Survey (GATS) questionnaire for waterpipe consumption was used for data gathering. Data were statistically analyzed by SPSS software. The prevalence of current waterpipe tobacco smoking was 17.6% .Waterpipe use prevalence in men was significantly more than women (24.2% vs. 11.3%). Multivariate analysis showed that age, sex, cigarette consumption, waterpipe consumption at home and ignorance of safety issues significantly influenced current waterpipe smoking (P = 0.001). Thus, prevalence of waterpipe smoking in Iranian adults is high and significant. Tackling waterpipe smoking should be considered in tobacco control programmes. However, further studies in this field are needed.

Evaluation of the prevalence of waterpipe tobacco smoking and its related factors in Tehran, Islamic Republic of Iran

This study is designed to evaluate the prevalence of waterpipe tobacco smoking and its related factors among Iranian adults. This is a cross-sectional study carried out during 2013/14 in Tehran, Islamic Republic of Iran, among 1830 citizens aged over 15 years. Sampling was through Stratified multistage cluster sampling with proportional allocation within strata. Global Adult Tobacco Survey [GATS] questionnaire for waterpipe consumption was used for data gathering. Data were statistically analyzed by SPSS software. The prevalence of current waterpipe tobacco smoking was 17.6% .Waterpipe use prevalence in men was significantly more than women [24.2% vs. 11.3%]. Multivariate analysis showed that age, sex, cigarette consumption, waterpipe consumption at home and ignorance of safety issues significantly influenced current waterpipe smoking [P = 0.001]. Thus, prevalence of waterpipe smoking in Iranian adults is high and significant. Tackling waterpipe smoking should be considered in tobacco control programmes. However, further studies in this field are needed

La présente étude est conçue pour estimer la prévalence de la consommation de tabac par pipe à eau et de ses facteurs associés dans la population adulte iranienne. Il s'agit d'une étude transversale, conduite entre 2013 et 2014 à Téhéran, en République islamique d'Iran, parmi 1830 citoyens âgés de plus de 15 ans. La technique utilisée était celle de l'échantillonnage en grappe stratifié à plusieurs niveaux avec allocation proportionnelle dans les strates. Le questionnaire de l'enquête mondiale sur le tabagisme chez les adultes pour la consommation de tabac par pipe à eau a été utilisé afin de collecter les données. Celles-ci ont été analysées sur le plan statistique à l'aide du logiciel SPSS. La prévalence de la consommation de tabac par pipe à eau au moment de l'étude était de 17,6%, et était plus importante chez les hommes que chez les femmes [24,2% contre 11,3%]. L'analyse multivariée a montré que l'âge, le sexe, la consommation de cigarettes, la consommation de pipe à eau à la maison et l'ignorance des questions de sécurité influençaient de façon significative la consommation de tabac par pipe à eau [p = 0,001]. Par conséquent, la prévalence de la consommation de tabac par pipe à eau est élevée et significative parmi les adultes iraniens. La question de la consommation de tabac par pipe à eau devrait être traitée dans le cadre des programmes de lutte antitabac. Néanmoins, d'autres études dans ce domaine sont requises