Metabolic brain disease最新文献

Ischemic stroke is a leading cause of disability and death in patients. Despite considerable recent advances in the treatment of ischemic stroke, only a limited number of effective neuroprotective agents are available for stroke. Green tea (Camellia sinensis) is a popular herbal plant, and numerous studies have indicated its health benefits for several diseases. Green tea is of interest due to its high content of catechin derivatives, including epicatechin, gallocatechin, epicatechin gallate, epigallocatechin, and epigallocatechin-3-gallate. This review tried to develop a feasible background for the potential effects of green tea and its bioactive derivatives concerning protection against ischemic stroke. Green tea's antioxidants, anti-inflammatory, anti-apoptotic, and neuroprotective effects are believed to be efficacious in stroke treatment. Evidence supports the idea that green tea can be used to assist in treating ischemic stroke.

Diabetes mellitus (DM) is a chronic disease characterized by elevated blood glucose levels caused by a lack of insulin production (type 1 diabetes) or insulin resistance (type 2 diabetes). It is well known that DM is associated with cognitive deficits and metabolic and neurophysiological changes in the brain. Glutamate is the main excitatory neurotransmitter in the central nervous system that plays a key role in synaptic plasticity, learning, and memory processes. An increasing number of studies have suggested that abnormal activity of the glutamatergic system is implicated in the pathophysiology of DM. Dysfunction of glutamatergic neurotransmission in the central nervous system can provide an important neurobiological substrate for many disorders. Magnetic resonance spectroscopy (MRS) is a non-invasive technique that allows a better understanding of the central nervous system factors by measuring in vivo the concentrations of brain metabolites within the area of interest. Here, we briefly review the MRS studies that have examined glutamate levels in the brain of patients with DM. The present article also summarizes the available data on abnormalities in glutamatergic neurotransmission observed in different animal models of DM. In addition, the role of gut microbiota in the development of glutamatergic alterations in DM is addressed. We speculate that therapeutic strategies targeting the glutamatergic system may be beneficial in the treatment of central nervous system-related changes in diabetic patients.

Most scholars believe that amyloid-beta (Aβ) has the potential to induce apoptosis, stimulate an inflammatory cascade, promote oxidative stress and exacerbate the pathological progression of Alzheimer's disease (AD). Therefore, it is crucial to investigate the deposition of Aβ in AD. At approximately 6 months of age, APP/PS1 double transgenic mice gradually exhibit the development of plaques, as well as spatial and learning impairment. Notably, the hippocampus is specifically affected in the course of AD. Herein, 6-month-old APP/PS1 double transgenic mice were utilized, and the differentially expressed (DE) proteins in the hippocampus were identified and analyzed using 4D label-free quantitative proteomics technology and parallel reaction monitoring (PRM). Compared to wild-type mice, 29 proteins were upregulated and 25 proteins were downregulated in the AD group. Gene Ontology (GO) enrichment analysis of biological processes (BP) indicated that the DE proteins were mainly involved in 'ribosomal large subunit biogenesis'. Molecular function (MF) analysis results were primarily associated with '5.8S rRNA binding' and 'structural constituent of ribosome'. In terms of cellular components (CC), the DE proteins were mainly found in 'polysomal ribosome', 'cytosolic large ribosomal subunit', 'cytosolic ribosome', and 'large ribosomal subunit', among others. Furthermore, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis demonstrated that the results were mainly enriched in the 'Ribosome signaling pathway'. The key target proteins identified were ribosomal protein (Rp)l18, Rpl17, Rpl19, Rpl24, Rpl35, and Rpl6. The PRM verification results were consistent with the findings of the 4D label-free quantitative proteomics analysis. Overall, these findings suggest that Rpl18, Rpl17, Rpl19, Rpl24, Rpl35, and Rpl6 may have potential therapeutic value for the treatment of AD by targeting Aβ.

Obsessive-compulsive disorder (OCD) is a neuropsychiatric disorder. Approximately, around 2% to 3% percent of the general population experience symptoms of OCD over the course of their lifetime. OCD can lead to economic burden, poor quality of life, and disability. The characteristic features exhibited generally in OCD are continuous intrusive thoughts and periodic ritualized behaviours. Variations in genes, pathological function of Cortico-Striato-Thalamo-Cortical (CSTC) circuits and dysregulation in the synaptic conduction have been the major factors involved in the pathological progression of OCD. However, the basic mechanisms still largely unknown. Current therapies for OCD largely target monoaminergic neurotransmitters (NTs) in specific dopaminergic and serotonergic circuits. However, such therapies have limited efficacy and tolerability. Drug resistance has been one of the important reasons reported to critically influence the effectiveness of the available drugs. Inflammation has been a crucial factor which is believed to have a significant importance in OCD progression. A significant number of proinflammatory cytokines have been reportedly amplified in patients with OCD. Mechanisms of drug treatment involve attenuation of the symptoms via modulation of inflammatory signalling pathways, modification in brain structure, and synaptic plasticity. Hence, targeting inflammatory signaling may be considered as a suitable approach in the treatment of OCD. The present review focuses mainly on the significant findings from the animal and human studies conducted in this area, that targets inflammatory signaling in neurological conditions. In addition, it also focusses on the therapeutic approaches that target OCD via modification of the inflammatory signaling pathways.

This study aims to assess the effects of exercise on cognitive impairment behavioral performance and neuroprotective mechanisms in diabetes mellitus (DM) animal models. PubMed, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang Database, VIP Database (VIP), and China Biomedical Literature Database (CBM) were systematically searched for studies investigating the impact of exercise on cognitive impairment in animal models of diabetes mellitus (DM) from the inception of these databases through July 2023. Rigorous quality assessments were conducted on the included literature. Primary outcome measures comprised fasting blood glucose (FBG) levels and performance in the Morris water maze test, while secondary outcomes focused on mechanisms related to neuroprotection. Statistical analysis of outcome data was conducted using RevMan 5.3 and R software. A total of 17 studies were included, encompassing 399 animals. The results of the meta-analysis of primary outcome measures revealed that, compared to the control group, exercise effectively reduced fasting blood glucose (FBG) levels in diabetic animal models. In the Morris water maze experiment, exercise also significantly decreased the escape latency of diabetic animal models, increased the number of platform crossings, improved the percentage of time spent in the target quadrant, extended the time spent in the target quadrant, and enhanced swimming speed. Meta-analysis of secondary outcome measures indicated that exercise effectively reduced Aβ deposition, attenuated oxidative stress, enhanced synaptic function, suppressed cellular apoptosis and neuroinflammation, and promoted neurogenesis. Exercise represents a promising non-pharmacological therapy with a positive impact on diabetes-related cognitive function and neuroprotection. Moreover, this study provides a theoretical foundation for further preclinical and clinical trials.

Long non-coding RNAs (lncRNAs) have been recently considered as one of the regulatory mechanisms of the nervous system. Hence, lncRNAs may be considered diagnostic biomarkers for bipolar disorder (BD). We aimed to investigate the expression of RMRP, CTC-487M23.5, and DGCR5 lncRNAs in bipolar patients. The levels of these three lncRNAs were measured in peripheral blood mononuclear cells (PBMCs) of 50 BD patients and 50 healthy subjects by real-time PCR. Moreover, we performed a ROC curve analysis between the gene expression and some clinical features of BD patients. Significant upregulation of RMRP and CTC-487M23.5 and no significant change in levels of DGCR5 was observed in BD individuals compared with controls. Also, we found upregulation of RMRP and downregulation of CTC-487M23.5 and DGCR5 in females with BD. The areas under the ROC curve (AUC) for RMRP and CTC-487M23.5 lncRNAs were 0.80 and 0.61, respectively. There was no significant correlation between the expression of these three lncRNAs and clinical features in PBMCs of BD patients. These results suggest a role for RMRP and CTC-487M23.5 in the pathogenesis of bipolar disorder. Moreover, the peripheral expression of these two lncRNAs might be beneficial as potential biomarkers for BD.

Classic galactosemia is a rare inborn error of metabolism that affects the metabolism of galactose, a sugar derived from milk and derivates. Classic galactosemia is caused by variants of the GALT gene, which lead to absent or misfolded forms of the ubiquitously present galactose-1-phosphate uridylyltransferase enzyme (GALT) driving galactose metabolites to accumulate, damaging cells from neurons to hepatocytes. The disease has different prevalence around the world due to different allele frequencies among populations and its symptoms range from cognitive and psychomotor impairment to hepatic, ophthalmological, and bone structural damage. The practice of newborn screening still varies among countries, dairy restriction treatment is a consensus despite advances in preclinical treatment strategies. Recent clinical studies in Duarte variant suggest dairy restriction could be reconsidered in these cases. Despite noteworthy advances in the classic galactosemia understanding, preclinical trials are still crucial to fully understand the pathophysiology of the disease and help propose new treatments. This review aims to report a comprehensive analysis of past studies and state of art research on galactosemia screening, its clinical and preclinical trials, and treatments with the goal of shedding light on this complex and multisystemic innate error of the metabolism.

Depression is one of the most prevalent severe CNS disorders, which negatively affects social lives, the ability to work, and the health of people. As per the World Health Organisation (WHO), it is a psychological disorder that is estimated to be a leading disease by 2030. Clinically, various medicines have been formulated to treat depression but they are having a setback due to their side effects, slow action, or poor bioavailability. Nowadays, flavonoids are regarded as an essential component in a variety of nutraceutical, pharmaceutical and medicinal. Isoflavones are a distinctive and important subclass of flavonoids that are generally obtained from soybean, chickpeas, and red clover. The molecules of this class have been extensively explored in various CNS disorders including depression and anxiety. Isoflavones such as genistein, daidzein, biochanin-A, formononetin, and glycitein have been reported to exert an anti-depressant effect through the modulation of different mediators. Fatty acid amide hydrolase (FAAH) mediated depletion of anandamide and hypothalamic-pituitary-adrenal (HPA) axis-mediated modulation of brain-derived neurotrophic factor (BDNF), monoamine oxidase (MAO) mediated depletion of biogenic amines and inflammatory signaling are the important underlying pathways leading to depression. Upregulation in the levels of BDNF, anandamide, antioxidants and monoamines, along with inhibition of MAO, FAAH, HPA axis, and inflammatory stress are the major modulations produced by different isoflavones in the observed anti-depressant effect. Therefore, the present review has been designed to explore the mechanistic interplay of various mediators involved in mediating the anti-depressant action of different isoflavones.