查看更多>>摘要:Here, we review data on ovariectomy (OVX) in rodents as a suitable model for estimation of anxiety-depressive disorders in women in the near- and menopause periods of life. In the first part, we review the effects of OVX on the development of anxiety and depressive-like behavior depending on the age of the animal, the time point of surgery, the time of testing after surgery, features of the tests, and other factors. We consider the combined effect of OVX and chronic stress and the replacement function of estrogens in OVX animals. The second part of the review is devoted to the mechanisms of OVX effects and replacement estrogen therapy on the development or prevention of anxiety and depressive-like behavior. The behavioral, hormonal, biochemical, molecular-cellular, and intracellular signaling mechanisms of estrogen action in OVX animals are also considered. The role of the hypothalamic-pituitary-adrenal system, neuroinflammatory/immune system, nitric oxide, monoaminergic systems, trophic factors, neurogenesis, and intracellular signaling, among others in these mechanisms are described.
查看更多>>摘要:The relevant scientific literature has accumulated an extensive array of data indicating the neuroprotective potential of creatine (Cr). However, while many recent experimental and clinical studies confirm the previously revealed neuroprotective therapeutic effects of Cr, the clinical results on certain diseases are uncertain. The primary purpose of this review is, on the one hand, to summarize the experimental data that unequivocally indicate the neuroprotective effectiveness of Cr. On the other hand, this publication seeks to discuss the latest controversies related to some of the clinical trials involving Cr, as well as its prospects for therapeutic and preventive use. As it emerges from the discussion of the presented material, the advantages of Cr as a food supplement are not limited to its use in high-intensity and rehabilitation physical exercises. Remarkably, can have much wider application, both among generally healthy people and various patient groups. Despite somewhat equivocal data from several clinical trials, most researchers are confident that further studies with improved protocols will confirm the neuroprotective therapeutic potential of Cr in neurodegenerative diseases. Already we can state the confirmed efficiency of Cr in Huntington's disease and traumatic brain damage. There is also promising evidence on the positive therapeutic effect of Cr in the case of such mental disorders as depression, post-traumatic stress disorder, and fibromyalgia. It is obvious that the protective potential of Cr as a natural adaptogen has not yet been fully uncovered; therefore, the spectrum of its areas for therapeutic and preventive application is expected to grow based on the results of the ongoing research activities.
Sokolov, A. Y.Osipchuk, A. V.Skiba, I. B.Amelin, A. V....
8页
查看更多>>摘要:In this review, we summarize the experimental and clinical data supporting the role of pituitary adenylate cyclase-activating peptide (PACAP) and vasoactive intestinal peptide (VIP) in the pathophysiology of primary headaches, including migraine. We provide evidence of the involvement of these mediators and their receptors in nociception and vascular tone regulation, especially within the trigeminovascular system. The anticephalalgic potential of pharmacological agents blocking the PACAP-ergic pathway is also discussed.
查看更多>>摘要:One of the most challenging tasks is identifying all the chemical interactions inside the human body. The interplay of vitamins and neurotransmitters is an intriguing topic to study to understand the body-brain relationship better. Schizophrenia is a severe brain disorder in which neurotransmitters play a crucial role. We find significantly less study to investigate the linkage between the two in schizophrenia. This study attempted to determine the link between various vitamins found in our daily diet and neurotransmitters in our brain that are important for optimal mental functioning, focusing on schizophrenia. We conducted a comprehensive evaluation of the relevant literature, examined the significance of vitamins in the human body, and paid attention to those essential for proper brain growth. We also studied the linkage of neurotransmitters and their alterations due to the influence of vitamins in schizophrenia patients. Our study finds that vitamin E has a subtle effect on the dysfunction of serotonin and glutamate, and vitamin D affects dopamine. These findings prove the association of vitamin intake and its effect on the onset of schizophrenia, influencing the responsible neurotransmitters. To our best knowledge, this is the first study to examine the most relevant literature and present these findings, which may improve the understanding of the neuroscience domain and help further research.
查看更多>>摘要:A hypothetical mechanism of resting tremor onset in Parkinson's disease has been proposed. This mechanism is based on modifications of the efficiency of excitatory inputs to the striatal spiny cells caused by dopamine deficiency. These modifications lead to a reorganization of activity in neural network, including the neocortex, thalamus, basal ganglia, cerebellum, as well as the subthalamic and pedunculopontine nuclei. As a result of this modification, the activity of striatonigral cells decreases, and causes disinhibition of neurons in the internal part of the globus pallidus. At the same time, the activity of striatopallidal cells increases leading to a decrease in the activity of neurons in the external part of the globus pallidus, and a subsequent decrease in their inhibitory effect on neurons in the internal part of the globus pallidus, as well as in the subthalamic nucleus and neocortex. As a result, the activity of neurons in these structures increases. Strengthening the GABAergic input from the internal part of the globus pallidus to the neurons of the subthalamic nucleus that leads to hyperpolarization of the neuronal membrane, contributes to the generation of burst discharges with a tremor frequency. An increase in the activity of neurons in the subthalamic nucleus leads to an increase in the excitation of their target cells in the pedunculopontine nucleus and deep cerebellar nuclei. The subsequent enhancement of the excitatory effect of the cerebellum on thalamic neurons is transmitted to the neocortex and striatum. According to the proposed mechanism, the degree of excitation of neurons in the subthalamic nucleus determines the tremor amplitude and explains the fact that the increase in activity in the cerebellum, thalamus, and neocortex correlates with the severity of tremor. It follows from the proposed mechanism that since selective agonists of dopamine D2 receptors and/or antagonists of adenosine A2A receptors should promote the induction of LTD on striatopallidal cells, weakening their inhibitory effect on neurons in the external part of the globus pallidus, and the subsequent increase in the inhibition of the subthalamic nucleus, these substances can be used to suppress resting tremor. These consequences of our hypothesis have experimental confirmation.
查看更多>>摘要:The aim of the study was to investigate brain GABAergic neurons and synaptic terminals in early postnatal development and aging. Wistar rat brain slices at different stages of postnatal development (from postnatal day 7 to 24 months) were used. Immunohistochemical staining of GABA synthesizing enzyme (glutamate decarboxylase isoform 67 or GAD67) was performed to reveal GABAergic structures. We described morphological changes that occur in the GABAergic system during postnatal development. In particular, it has been shown that synaptic terminals are predominantly localized in cortical layer 1 in 7-day-old animals. Our findings suggest that Cajal-Retzius cells are not GABAergic. GABAergic neurons were found in young and old animals in the subventricular zone. We found that the epithelial layer of choroid plexus contains GAD67 by the end of the first month of postnatal development. In this regard, these epithelial cells may be a source of extrasynaptic GABA, which enters the cerebrospinal fluid and then nervous tissue of the brain.
Belenichev, I. F.Aliyeva, E. G.Kamyshny, O. M.Bukhtiyarova, N. V....
8页
查看更多>>摘要:Prenatal hypoxia (PH) causes pathological changes in the brain and can lead to irreversible long-term disorders of brain development and the emergence of neuropsychiatric pathologies in children. Pharmacological correction of post-hypoxic disorders of the central nervous system is a priority in modern medicine. The aim of this work was to study the neuroprotective effects of Angiolin, Thiotriazoline, Tamoxifen, Glutoredoxin, Cerebrocurin, an IL-1b antagonist (RAIL), Mexidol, and L-arginine in comparison with the reference drug Piracetam in terms of their effect on the expression of endogenous neuroprotection factors for further substantiation of their use for treating prenatal CNS lesions in a model of chronic hemic PH. The expression of HSP70, HIF-1, and c-fos mRNAs and the content of HSP70 in the cytoplasmic and mitochondrial fractions of the brain of 60 day old rat pups subjected to PH were studied using real-time PCR and enzyme-linked immunosorbent assay. We found that chronic PH leads to the inhibition of transcriptional processes in neurons and the suppression of HIF1a, HSP70, and c-fos synthesis. The studied drugs modulated the HSP70-mediated mechanisms of endogenous neuroprotection. The most active among HSP70 modulators in chronic PH were Cerebrocurin (150 mu L/kg) and Angiolin (50 mg/kg) which surpass the other drugs studied in the level of HSP70 and HIF-1 alpha mRNA expression, as well as HSP70 protein concentration in the brain of experimental animals, and can be viewed as promising neuroprotective agents in complex therapy after PH.
Mendzheritsky, A. M.Prokofiev, V. N.Lyangasova, O. V.Fomenko, M. P....
9页
查看更多>>摘要:This study presents the results of a comparative analysis of the expression of genes regulating synaptic plasticity, spatial learning ability, and the preservation of the acquired skill in 3-month-old and 18-month-old animals with streptozotocin-induced diabetes. The Morris maze was used to assess spatial learning. In the hippocampus, the relative level of transcripts of the c-fos, c-jun, Egr-1, and Cyt-c genes was investigated using real-time polymerase chain reaction. On the third day of testing in the Morris water maze, the time to reach the platform in 18-month-old rats exceeded the respective values of 3-month-old rats, as seen after modeling of streptozotocin-induced diabetes. The expression levels of the c-fos, c-jun, and Egr-1 genes in 3-month-old rats increased both in response to the development of spatial learning and modeling of diabetes; in 18-month-old rats, a decrease in the level of expression of this gene was observed in the model of streptozotocin-induced diabetes. In both groups, we observed an increase in the level of expression of the Cyt-c gene in diabetes relative to control and, in 18-month-old rats, the increase in this index was more pronounced.
Konkov, V. G.Kudrin, V. S.Narkevich, V. B.Efimova, A. O....
7页
查看更多>>摘要:Alcohol-related mental health problems, including an increased risk of development of anxiety-depressive disorders and alcohol addiction, are often passed down from generation to generation. Currently, there are no studies that consider the effect of prolonged alcohol exposure on the content of neurotransmitter monoamines and neurotransmitter amino acids in the brain structures responsible for the formation of emotional and motivational behavior patterns in the first F1 generation in the absence of direct alcohol exposure to the fetus. The aim of the present work was to study the anxiety behavior and neurochemical changes in the insular cortex and anterior cingulate cortex (ACC) in the intact offspring of rats that consumed ethanol solution for 30 weeks before mating. In the "elevated plus maze" test, females spent more time in open arms compared to males, however, no significant differences in the stress response between the offspring of rats exposed to and not exposed to ethanol were found. In ex vivo experiments, a decrease was observed for the insular cortex in the turnover of extracellular dopamine in animals of both sexes (p < 0.05) and multidirectional shifts in the total turnover of dopamine in the absence of changes in the content of neurotransmitter amino acids. In the ACC, a decrease in the glycine content (p < 0.05) was observed only in females. The data obtained indicate that prolonged oral administration of ethanol induces sex-dependent changes in the content of neurotransmitter monoamines and amino acids in the brain structures that determine the formation of emotional and motivational behavior in previously unaffected offspring.
Ghaedi, KamranPeymani, MaryamEsfahani, Mohammad Hossein NasrDana, Shadab...
7页
查看更多>>摘要:Parkinson's disease is known as the second most common neurodegenerative disorder that commonly affects the older population. MicroRNAs are categorized as short non-coding RNAs (19-24 nt) involved in the post-transcriptional regulation of gene expression in multicellular organisms. They can influence both stability and translation of mRNAs. Recent studies suggested that miR-141 which is well-known in oxidative-stress pathway is up-regulated in some neurodegenerative diseases including the Alzheimer disease. This study was intended to evaluate the miR-141 expression and its predicted target gene in the MPP+ treated differentiated SH-SY5Y cells. In silico studies were also considered by using miRWalk and TargetScan databases to determinate any possible target of miR-141. Moreover, SHSY-5Y cells were allowed to be exposed to MPP+ as a parkinsonian neurotoxin. The quantification of the expression levels of miR-141 and the predicted target mRNA was done by using RT-qPCR to show their expression pattern. Results showed the significant up-regulation of miR-141 during the treatment of human SH-SY5Y cells with MPP+, inducing oxidative stress and apoptosis. Furthermore, transcript level of SIRT1 in these cells exhibited significant down-regulation under MPP+ treatment. In addition, exposure to MPP+ raised the apoptotic rate, leading to ROS accumulation and oxidative stress. To summarize, it was found that miR-141 expression could trigger the PD-related pathogenic processes and decreased SIRT1 expression is associated with increased miR-141 expression in MPP+ treated SHSY-5Y cells.