Acta neurobiologiae experimentalis最新文献

Autism spectrum disorders are complex behavioral disorders that can be caused by exposure to valproic acid (VPA) during pregnancy. A therapeutic role for exercise training has been reported in many neurological diseases and problems, including autism. We aimed to evaluate various intensities of endurance exercise training and investigate its effects on oxidative and antioxidant factors in the liver of young males in a rat model of autism. Female rats were divided into a treatment (autism) and a control group. The autism group received VPA intraperitoneally on day 12.5 of pregnancy and the control pregnant females received saline. On the 30th day post‑birth, a social interaction test was performed on the offspring to confirm autistic‑like behavior. Offspring were divided into three subgroups: no exercise, mild exercise training, and moderate exercise training. Then the oxidative index of malondialdehyde (MDA) and the antioxidant indices of superoxide dismutase (SOD), total antioxidant capacity (TAC), and catalase in liver tissue were examined. The results of this study showed that both indices of sociability and social novelty decreased in the autism group. MDA levels in the liver of the autistic group increased, and moderate exercise training was shown to reduce the levels. Catalase and SOD activity as well as TAC levels decreased in the autism group, and moderate‑intensity exercise training was shown to increase the values. Parameters of hepatic oxidative stress were altered in VPA‑induced autism, and moderate‑intensity endurance exercise training was demonstrated to have beneficial effects on hepatic oxidative stress factors by modul ating the antioxidant/oxidant ratio.

In the central nervous system, long‑term effects of a vagotomy include disturbance of monoaminergic activity of the limbic system. Since low vagal activity is observed in major depression and autism spectrum disorder, the study aimed to determine whether animals fully recovered after subdiaphragmatic vagotomy demonstrates neurochemical indicators of altered well‑being and social component of sickness behavior. Bilateral vagotomy or sham surgery was performed in adult rats. After one month of recovery, rats were challenged with lipopolysaccharide or vehicle to determine the role of central signaling upon sickness. Striatal monoamines and met‑enkephalin concentrations were evaluated using HPLC and RIA methods. We also defined a concentration of immune‑derived plasma met‑enkephalin to establish a long‑term effect of vagotomy on peripheral analgesic mechanisms. The data indicate that 30 days after vagotomy procedure, striatal dopaminergic, serotoninergic, and enkephalinergic neurochemistry was altered, both under physiological and inflammatory conditions. Vagotomy prevented inflammation‑induced increases of plasma met‑enkephalin - an opioid analgesic. Our data suggest that in a long perspective, vagotomized rats may be more sensitive to pain and social stimuli during peripheral inflammation.

Both cannabinoid and opioid receptors are involved in pain behavior. The administration of morphine and cannabis in rats has been shown to decrease thyroid weight and thyroid‑stimulating hormone (TSH) levels. We hypothesized that the third ventricle, due to its adjacency to the hypothalamus, is involved in the modulation of hypothalamic‑pituitary‑thyroid axis activity and descending pain pathways. The present study examined the effect of intra‑third ventricle administration of morphine and cannabis agents on the modulation of pain behavior in normal, hypothyroid (increased serum TSH), and hyperthyroid (decreased serum TSH) rats using the tail‑flick test. The results indicated that intra‑third ventricle injection of AM251 (CB1 receptor antagonist) caused hyperalgesia, while intra‑third ventricle administration of ACPA (CB1 receptor agonist) and morphine produced analgesia in normal, hypothyroid, and hyperthyroid rats. A non‑effective dose of morphine (0.5 μg/rat) did not attenuate hyperalgesia induced by an effective dose of AM251. Co‑injection of ACPA and morphine into the third ventricle induced anti‑nociceptive effect in normal, hypothyroid, and hyperthyroid rats. An isobolographic analysis demonstrated a synergistic effect between ACPA and morphine in the production of the anti‑nociceptive effect. Consequently, the third ventricle may modulate pain behavior induced by cannabinoid and opioid receptors via descending pain pathways in normal, hypothyroid, and hyperthyroid rats.

The potential of minocycline to protect against methylphenidate‑induced neurodegeneration has been extensively reported in the literature but the mechanism of action is still unknown. This study aims to determine the role of mitochondrial chain enzymes and redox homeostasis on the neuroprotective effects of minocycline in methylphenidate‑induced neurodegeneration. Wistar adult male rats were randomly assigned to the seven experimental groups: Group 1 received saline solution; Group 2 received methylphenidate (10 mg/kg, i.p.); Groups 3, 4, 5, and 6 received methylphenidate and minocycline for 21 days; Group 7 received minocycline alone. Cognition was evaluated with the Morris water maze test. Activity of the hippocampal mitochondrial quadruple complexes I, II, III and IV, mitochondrial membrane potential, adenosine triphosphate (ATP) levels, total antioxidant capacity, and reactive oxygen species were determined. Treatment with minocycline inhibited methylphenidate‑induced cognitive dysfunction. Minocycline treatment increased mitochondrial quadruple complex activities, mitochondrial membrane potential, total antioxidant capacity, and ATP levels in the dentate gyrus and cornu ammonis‑1 (CA1) areas of the hippocampus. Minocycline is likely to confer neuroprotection against methylphenidate‑induced neurodegeneration and cognition impairment by regulating mitochondrial activity and oxidative stress.

Crocin and Terminalia chebula (T. chebula) were proven to have neuroprotective effects. In this study, we evaluated the preventive effects of crocin and alcoholic extract of the T. chebula alone and in combination to examine their efficacy against chronic restraint stress (CRS)‑induced cognitive impairment, anxiety‑like behaviors, hippocampal synaptic plasticity deficit as well as neuronal arborization damage in the hippocampal CA1 neurons. Over 14 consecutive days, animals received crocin, T. chebula, or their combination (5 min before CRS). The elevated plus‑maze results showed that crocin and T. chebula alone and in combination treatment significantly increased the time spent in open arms, percentage of open arm entries, and head dipping as compared with the CRS group. Barnes maze results showed that administration of crocin and T. chebula alone and their combination significantly improves spatial memory indicators such as distance traveled, latency time to achieving the target hole, and the number of errors when compared to the CRS group. These learning deficits in CRS animals correlated with a reduction of long-term potentiation (LTP) in hippocampal CA1 synapses, which both T. chebula and crocin treatment improved field excitatory postsynaptic potentials (fEPSP) amplitude and fEPSP slope reduction induced by CRS. Golgi‑Cox staining showed that T. chebula and crocin treatment increased the number of dendrites and soma arbors in the CA1 neurons compared with the CRS group. Our results suggest that both T. chebula and crocin attenuated CRS‑induced anxiety‑like behaviors, memory impairment, and synaptic plasticity loss in hippocampal CA1 neurons. We found no significant difference between single treatments of T. chebula or crocin and their combination in protecting CRS‑induced anxiety‑like behaviors, memory impairment, and synaptic plasticity loss in hippocampal CA1 neurons.

Emerging hypotheses in the pathophysiology of major depressive disorder (MDD) suggest important role of neurotrophic factors and oxidative stress. This study assessed the effect of milnacipran (a dual serotonin‑noradrenaline reuptake inhibitor) on brain‑derived neurotrophic factor (BDNF) and oxidative stress biomarkers i.e., malondialdehyde (MDA), glutathione‑s‑ transferase (GST) and glutathione reductase (GR) in patients of MDD. Thirty patients (aged 18 to 60 years) with MDD diagnosed by DSM‑IV criteria, with Hamilton Depression Rating scale (HAM‑D) score ≥ 14 were included in the study. Patients were given milnacipran in the doses of 50‑100 mg once daily. Patients were followed up for 12 weeks. HAM‑D score at the start of treatment was 17.8±1.7 which significantly reduced to 8.9±3.1 at 12 weeks of treatment. In responders, the plasma BDNF levels increased significantly at 12 weeks post treatment. There was no significant change in the pre‑ and post‑treatment values of oxidative stress parameters (MDA, GST and GR) after 12 week treatment. Milnacipran is effective and well tolerated in MDD patients, and its therapeutic response is associated with an increase in plasma BDNF levels. However, milnacipran did not affect oxidative stress biomarkers.

Hepatic encephalopathy (HE) is a neuropsychiatric hepatic‑induced syndrome in which several factors are involved in promoting brain perturbations, with ammonia being the primary factor. Motor impairment, incoordination, and gut dysbiosis are some of the well‑known symptoms of HE. Nevertheless, the link between the direct effect of hyperammonemia and associated gut dysbiosis in the pathogenesis of HE is not well established. Thus, this work aimed to assess motor function in hyperammonemia and gut dysbiosis in mice. Twenty‑eight Swiss mice were distributed into three groups: two‑week and four‑week hyperammonemia groups were fed with an ammonia‑rich diet (20% w/w), and the control group was pair‑fed with a standard diet. Motor performance in the three groups was measured through a battery of motor tests, namely the rotarod, parallel bars, beam walk, and static bars. Microbial analysis was then carried out on the intestine of the studied mice. The result showed motor impairments in both hyperammonemia groups. Qualitative and quantitative microbiological analysis revealed decreased bacterial load, diversity, and ratios of both aerobic and facultative anaerobic bacteria, following two and four weeks of ammonia supplementation. Moreover, the Shannon diversity index revealed a time‑dependent cutback of gut bacterial diversity in a treatment‑time‑dependent manner, with the presence of only Enterobacteriaceae, Streptococcaceae, and Enterococcaceaeat at four weeks. The data showed that ammonia‑induced motor coordination deficits may develop through direct and indirect pathways acting on the gut‑brain axis.