Neurochemical Journal最新文献

Abstract

Two periods of autophagy activation with a different significance for the development of resistance were demonstrated in the model of neuronal resistance to the toxic glutamate challenge (trophic factor deprivation). The autophagy inhibitor 3-methyladenine (3-MA) at a concentration of 1.25 mM significantly suppressed resistance development but only if applied immediately after deprivation of trophic factors. Inhibition of autophagy with 3-MA during deprivation did not affect resistance production. In addition, activation of autophagy caused a decrease in caspase-3 activity, although the mechanism of this process remains unclear. We hypothesize that development of resistance in neurons is mediated by a decrease in caspase-3 activity caused by autophagy activation.

Abstract

To analyse the structural characteristics and fibre integrity of white matter in patients with major depressive disorder (MDD) and its relationship with depressive symptoms. Patients with MDD admitted to Wenzhou Seventh People’ Hospital between September 2021 and May 2023 were recruited as participants in the experimental group, and healthy volunteers matching in gender, age and years of education were recruited during the same period as the control group. The two groups were compared in terms of fractional anisotropy (FA), mean diffusivity (MD) and axial diffusivity (AD). The relationship between the white matter volume and the values of FA, MD and AD in different brain regions and the severity of depressive symptoms in the experimental group was analysed. Fifty-eight patients were included in the experimental group, and 60 healthy controls in the control group. In the experimental group, the white matter volume of the right inferior frontal gyrus was negatively correlated with the Hamilton depression rating scale (HAMD-17) score (r = ‒0.355, P < 0.05), and the left parietal gyrus was negatively correlated with the HAMD-17 score (r = –0.361, P < 0.05). The FA value in the occipital radiations of the corpus callosum of the white matter was negatively correlated with the HAMD-17 score (r = –0.410, P < 0.05). Moreover, the MD value of the left and right anterior thalamic radiation of white matter was negatively correlated with the HAMD-17 score (r = –0.389, P < 0.05; r = –0.489, P < 0.01, respectively), and the AD value showed a negative correlation with the HAMD-17 score (r = –0.446, –0.405, respectively, both P < 0.05). Patients with MDD suffer from decreased white matter volume and impaired fibre integrity of white matter, including in the parietal lobe, corpus callosum, corticospinal tract and inferior longitudinal tract. Abnormalities in white matter structure and fibre integrity have a close bearing on the severity of MDD.

Abstract

Intracranial hemorrhage (ICH) is the most critical secondary lesion of traumatic brain injury (TBI). Identifying novel biomarkers for the prediction of ICH occurrence and development in TBI patients would benefit the prognosis of TBI and provide targeted nursing strategies for ICH secondary to TBI. The study enrolled a total of 208 TBI patients, where 105 patients had ICH. Serum samples were collected and analyzed with PCR to evaluate the expression of miR-885-5p. The significance of miR-885-5p in predicting the risk and progression of ICH in TBI patients was assessed. Microglia was induced by lipopolysaccharide (LPS) and transfected with miR-885-5p mimic. The inflammation in microglia was estimated by the levels of TNF-α, IL-6, and IL-1β using ELISA. Significant downregulation of miR-885-5p was observed in ICH patients secondary to TBI, which was identified as a risk factor for ICH and discriminated TBI-ICH patients from TBI patients without secondary lesions. Reduced serum miR-885-5p was significantly associated with lower GCS score, lower NIHSS score, increasing intracranial hemorrhage, increasing edema volume of peripheral tissues, and dysregulated coagulation function of ICH patients. In microglia, LPS induced the downregulation of miR-885-5p and increasing levels of TNF-α, IL-6, and IL-1β. The overexpression of miR-885-5p could alleviate LPS-induced inflammation in microglia. Downregulated miR-885-5p predicted the occurrence and severity of ICH secondary to TBI and regulated neuroinflammation in microglia.

Abstract

Glioma accounts for 80% of malignant central nervous system, with high incidence and extremely difficult to cure. However, for the role of ER stress apoptosis in tumor has caused great attention, the neuronal polarity molecule glycogen synthase kinase-3 β(GSK-3 β) endoplasmic network stress apoptosis pathway in tumor mechanism is a hot research in recent years, but for GSK-3 β ER stress apoptosis pathway in different levels of glioma research is extremely rare. In this experiment, we jointly explored the significance of GSK-3 β ER apoptosis pathway in different grades of glioma, which provided a strong basis for the precise treatment of glioma. 35 inpatients from December 2021 to December 2022 were enrolled into the different grades of glioma group and the normal control group. Tumor tissue was classified according to medical pathology. The other five normal brain tissues were obtained from the normal brain tissue of the fistula created in non-functional areas. One of the brain samples was stored for the apoptosis index (AI) of TUNEL (chromogenic method), and another part was stored in liquid nitrogen for the expression of GRP78, IRE 1, ATF 6, PERK, p-Tyr216-GSK-3 β, p-Ser 9-GSK-3 β, and Caspase-3. The AI values of different grades of glioma and normal control groups showed that the normal control, low-grade glioma and high-grade glioma groups were 8. 131 ± 0.234, 68.523 ± 1.392 and 22. 421 ± 0.236, respectively. The AI value was higher in the glioma group than in the normal controls (P < 0.05), while the AI value in the glioma group was negatively correlated with its malignancy (r = –0.725, P = 0.000). Western blot showed: compared with the normal control group, apoptosis initiation protein GRP78 expression, IRE 1, ATF 6, PERK decreased (P < 0.05); pathway key protein p-Ser 9-GSK-3 β increased, and p-Tyr216-GSK-3 β decreased (P < 0.05); pathway executive protein Caspase-3 increased (P < 0.05). However, the apoptosis initiation protein GRP78, IRE 1, ATF 6, PERK increased (P < 0.05); pathway key protein p-Ser 9-GSK-3 β decreased and p-Tyr216-GSK-3 β was increased (P < 0.05); pathway execution protein Caspase-3 expression decreased (P < 0.05). Conclusion: the AI value of low-grade glioma is higher than that of high-grade glioma, indicating that the progression of brain glioma may inhibit cell apoptosis. The increased apoptosis index and the expression changes of GSK-3 β ER stress cell apoptosis pathway in the glioma group indicate that the apoptosis pathway in GSK-3 β ER stress cells was initiated and executed in glioma. In low-grade glioma cells, there may be a mechanism to inhibit IRE 1, ATF 6, PERK, and p-Tyr216-GSK-3 β expression, which further promotes cell apoptosis and inhibited tumor progression. And with the progression of glioma, The expression of IRE 1, ATF 6, PERK, GRP78, and p-Tyr216-GSK-3 β was gradu

Abstract—The aim of the present work was to study the dynamics of neurotransmitter amino acids after acute Noopept (a dipeptide analogue of piracetam used in clinical practice as a nootropic agent) administration in intact and long-term ethanol (ETOH) exposed rats. Albino male rats were given 10% (vol/vol) ETOH solution as the only source of fluid 24 h/7 days per week (n = 5). Also we used intact rats of the same age which had no access to ethanol (n = 5). The excitatory and inhibitory amino acids in the extracellular space of the dorsal hippocampus in freely moving intact and ETOH-exposed rats during prolonged alcohol deprivation were measured using the intracerebral microdialysis method followed by HPLC/ED. There were no significant differences in the level of neurotransmitter amino acids between ETOH-exposed and intact animals. For the first time, in vivo experiments showed the effect of Noopept (1.5 mg/kg, i.p.) on the level of excitatory amino acids (an increase in aspartate by 2.38 times and glutamate by 2.28 times) along with an increase in the level of the inhibitory amino acid glycine by 3.13 times only in intact rats. Thus, in ETOH-exposed rats under the adaptive rearrangements in prolonged ethanol withdrawal, the neurochemical mechanisms of the hippocampus seem to be characterized by insensitivity to an acute Noopept administration. Animal neurochemical studies of long-term alcohol-induced changes in the mediator amino acids in the CNS may be of practical importance for the development of optimal strategies and pharmacotherapy.

Abstract

Parkinson’s disease is the most common neurodegenerative movement disorder, the pathogenesis of which is partly related with oxidant status and inflammatory responses. The administration of citral with antioxidant and anti-inflammatory properties may alleviate the negative effects of Parkinson. The present study aimed to assess the effects of citral nanoliposome on Parkinson’s treatment in a rat model. In this study, citral nanoliposome was successfully produced through employing a facile method. Additionally, 40 Wistar rats were divided into four groups (n = 10), one of which was considered as Sham and received no treatment. However, the other groups were administrated with rotenone, and/or treated with 5 and 10 mg/kg of citral for 21 days. Behavioral responses were evaluated based on the forced swimming test and hippocampal-dependent memory deficit. The rates were examined for tissue lipid peroxide (LPO), as well as the activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx) in brain. Further, they were investigated in terms of expression of brain-derived neurotrophic factor (BDNF), tumor necrosis factor (TNF-α), interleukin-6 (IL-6), and nuclear factor kappa B (NF-κB). The results suggested more immobility, higher LPO level, and a rise in the expression of TNF-α, IL-6, and NF-κB (P = 0.001) following rotenone administration. Furthermore, this treatment decreased climbing, retention latency, SOD and GPx activities, and BDNF expression (P = 0.001). The use of citral, especially in higher dose, reversed all the adverse effects of rotenone on behavioral responses, antioxidant status, BDNF, and inflammatory genes. Parkinson represents a closed relationship with movement deficiency, increased inflammation, and reduced oxidant status. Citral administration can be considered as a therapeutic option following future studies.

Abstract

Glioma is the most common type of primary craniocerebral tumor. Understanding the molecular mechanisms of glioma occurrence and development will provide strategies for effectively treating glioma. Proline-rich protein 11 (PRR11) is a protein which is widely overexpressed in different tumors. TCGA data analysis showed that PRR11 expression was up-regulated in glioma tissues, but its role still needs to be further studied. Here, the role of PRR11 in glioma progression and the mechanism were investigated. We found PRR11 was overexpressed in glioma cells. Depletion of PRR11 suppressed the growth of glioma cells as well as induced cell cycle arrest. We further found PRR11 ablation induced the autophagy of glioma cells. Furthermore, knockdown of PRR11 restrained the activation of Akt/mTOR pathway, thereby suppressing the proliferation of glioma cells. We thought PRR11 could serve as a target for glioma therapy.

Abstract—Glycoprotein N-cadherin (Neuronal cadherin) belongs to the family of calcium-dependent cell adhesion molecules, representing a key element that carries out intercellular contacts in brain neurons. However, it is involved not only in the mechanical connection of neurons but also influences the specifics of the further development and functional state of the neuron. This is due to the active interaction of N-cadherin with many proteins at the pre- and post-synapse, which initiates a cascade of reactions that provide processes such as long-term potentiation (underlying learning and memory), morphogenesis, neuronal recognition, activation of receptors (NMDA and AMPA types), and regulation of cytoskeleton formation. This polyfunctionality is necessary for specific neurons to connect to each other in a certain way, and such adhesion leads to the coordination of cell behavior through intercellular signaling and spatio-temporal control of differential gene expression. Mutations in the genes responsible for the expression of N-cadherin lead to various disorders of the functional activity of the synapse and the processes of spatial orientation and memory. Thus, involvement in important neuroplastic processes regulating cognitive functions and behavior determines interest in studying the effect of drugs on N-cadherin. In particular, N-cadherin deserves closer consideration by pharmacologists as a potential target in the mechanism of action of various psychoactive substances.

Abstract

Differentiation and self-renewal capacity of neural stem cells are essential for the development and function of brain. Anesthesia exposure inhibits the differentiation and self-renewal capacity of neural stem cells, impairs neurological function during the development of brain. SOX5 exerted neuroprotective effect against ischemic stroke, and regulated chondrogenic differentiation of stem cells. However, the effect and mechanism of SOX5 on sevoflurane-induced neurotoxicity of neural stem cells have not been reported. Firstly, neural stem cells were isolated from hippocampus of neonatal rats. Results showed that the neural stem cells formed neurospheres, and expressed NESTIN. The isolated neural stem cells were then exposed to sevoflurane anesthesia. Sevoflurane exposure reduced expression of NESTIN, decreased cell viability and suppressed cell proliferation of neural stem cells, thus inhibiting the differentiation and self-renewal capacity of neural stem cells. Secondly, SOX5 was down-regulated in sevoflurane-induced neural stem cells. Over-expression of SOX5 enhanced cell viability of sevoflurane-induced neural stem cells, and promoted the cell proliferation. Moreover, sevoflurane induced cell cycle arrest at G0/G1 phase and promoted the cell apoptosis in neural stem cells. Over-expression of SOX5 attenuated sevoflurane-induced increase of G0/G1 ratio and apoptosis in neural stem cells. Thirdly, sevoflurane-induced decrease of phosphorylated PI3K (p-PI3K) and p-AKT expression in neural stem cells were reversed by SOX5 over-expression. In conclusion, SOX5 attenuated sevoflurane-induced toxicity in neural stem cells through inactivation of PI3K/AKT pathway.

Abstract—A possible mechanism is proposed for the influence of oxytocin and vasopressin on the functioning of the neural network in the CNS, in which olfactory information is processed and stored, and which plays an important role in social behavior. The effect of these neuropeptides on postsynaptic receptors associated with Gq/11 proteins contributes to the induction of long-term potentiation of excitatory synaptic inputs to the main projection cells and to inhibitory interneurons in the prefrontal cortex, hippocampus, piriform cortex, anterior olfactory nucleus, olfactory bulb and nucleus accumbens, including the olfactory tubercle. As a result of disynaptic inhibition in each of the structures, the signal-to-noise ratio is improved and the transmission of strong signals through projection neurons to their target cells is facilitated. Due to the fact that oxytocin promotes the release of dopamine by the neurons of the ventral tegmental area, the conditions for processing and memorizing olfactory information in the interconnected olfactory and hippocampal neural networks, including cortical and subcortical structures, are improved, and attention is also included in this processing. Long-term modification of the effectiveness of interneuronal connections in these networks under the influence of oxytocin and dopamine contributes to the formation and stabilization of contrasting neuronal representation of odors formed in cortical areas. Orientation of attention increases the significance of socially important olfactory stimuli and improves the conditions for the functioning of the reinforcement system necessary for adequate social behavior. Taking into account the known data on the correlation between social behavior and the density of oxytocin and vasopressin receptors on neurons of different structures, understanding the mechanisms of the influence of these neuropeptides on the functioning of the olfactory system can be useful for finding ways to correct behavior if necessary.