The Role of Gut-derived Short-Chain Fatty Acids in Multiple Sclerosis
AbstractMultiple sclerosis (MS) is a chronic condition affecting the central nervous system (CNS), where the interplay of genetic and environmental factors influences its pathophysiology, triggering immune responses and instigating inflammation. Contemporary research has been notably dedicated to investigating the contributions of gut microbiota and their metabolites in modulating inflammatory reactions within the CNS. Recent recognition of the gut microbiome and dietary patterns as environmental elements impacting MS development emphasizes the potential influence of small, ubiquitous molecules from microbiota, such as sho...
Source: NeuroMolecular Medicine - April 17, 2024 Category: Neurology Source Type: research
Drug Treatment Attenuates Retinal Ganglion Cell Death by Inhibiting Collapsin Response Mediator Protein 2 Phosphorylation in Mouse Models of Normal Tension Glaucoma
This study evaluated the impact of the natural compounds huperzine A (HupA) and naringenin (NAR), which have therapeutic effects against glutamate excitotox icity and oxidative stress, on inhibiting CMRP2 phosphorylation in mice intravitreally injected withN-methyl-d-aspartate (NMDA) and GLAST mutant mice. Results of the study demonstrated that HupA and NAR significantly reduced RGC degeneration and thinning of the inner retinal layer, and inhibited the elevated CRMP2 phosphorylation. These treatments protected against glutamate excitotoxicity and suppressed oxidative stress, which could provide insight into developing new...
Source: NeuroMolecular Medicine - April 15, 2024 Category: Neurology Source Type: research
Circular RNA-GRIN2B Suppresses Neuropathic Pain by Targeting the NF- κB/SLICK Pathway
AbstractThe role of circular RNAs (circRNAs) in neuropathic pain is linked to the fundamental physiological mechanisms involved. However, the exact function of circRNAs in the context of neuropathic pain is still not fully understood. The functional impact of circGRIN2B on the excitability of dorsal root ganglion (DRG) neurons was investigated using siRNA or overexpression technology in conjunction with fluorescence in situ hybridization and whole-cell patch-clamp technology. The therapeutic efficacy of circGRIN2B in treating neuropathic pain was confirmed by assessing the pain threshold in a chronic constrictive injury (C...
Source: NeuroMolecular Medicine - April 10, 2024 Category: Neurology Source Type: research
The Relationship Between CYP46A1 Polymorphism and Suicide Risk: A Preliminary Investigation
This study examines the association betweenCYP46A1 polymorphisms, specifically SNPs rs754203 and rs4900442, and suicide risk in a Mexican MDD patient cohort. Our study involved 188 unrelated suicide death victims, 126 MDD patients, and 144 non-suicidal controls. Genotypic and allelic frequencies were assessed using the Real Time-polymerase chain reaction method, and associations with suicide risk were evaluated using chi-square tests. The study revealed significant differences in allelic and genotypic frequencies in rs754203 SNP between suicide death and controls. TheCYP46A1 rs754203 genotype G/G was significantly linked w...
Source: NeuroMolecular Medicine - April 9, 2024 Category: Neurology Source Type: research
Inhibition of p70 Ribosomal S6 Kinase (S6K1) Reduces Cortical Blood Flow in a Rat Model of Autism-Tuberous Sclerosis
In this study, we investigated whether inhibiting a component of the mTOR signaling pathway, p70 ribosomal S6 kinase (S6K1), would yield comparable effects. Control Long Evans and Eker rats were divided into vehicle and PF-4708671 (S6K1 inhibitor, 75 mg/kg for 1 h) treated groups. Cerebral regional blood flow (14C-iodoantipyrine) was determined in isoflurane anesthetized rats. We found significantly increased basal cortical (+ 32%) and hippocampal (+ 15%) blood flow in the Eker rats. PF-4708671 significantly lowered regional blood flow in the cortex and hippocampus of the Eker rats. PF-4708671 did not significantly...
Source: NeuroMolecular Medicine - April 4, 2024 Category: Neurology Source Type: research
Tetramethylpyrazine Nitrone Promotes the Clearance of Alpha-Synuclein via Nrf2-Mediated Ubiquitin –Proteasome System Activation
In conclusion, TBN promotes the clearance of α-syn via Nrf2-mediated UPS activation , and it may serve as a potentially disease-modifying therapeutic agent for PD. (Source: NeuroMolecular Medicine)
Source: NeuroMolecular Medicine - April 3, 2024 Category: Neurology Source Type: research
An Emerging Role for Enhancer RNAs in Brain Disorders
AbstractNoncoding DNA undergoes widespread context-dependent transcription to produce noncoding RNAs. In recent decades, tremendous advances in genomics and transcriptomics have revealed important regulatory roles for noncoding DNA elements and the RNAs that they produce. Enhancers are one such element that are well-established drivers of gene expression changes in response to a variety of factors such as external stimuli, cellular responses, developmental cues, and disease states. They are known to act at long distances, interact with multiple target gene loci simultaneously, synergize with other enhancers, and associate ...
Source: NeuroMolecular Medicine - March 28, 2024 Category: Neurology Source Type: research
Acetylation of c-Myc at Lysine 148 Protects Neurons After Ischemia
This study focuses on understanding the role of c-Myc, a cancer-associated transcription factor, in the penumbra following ischemic stroke. While its involvement in cell death and survival is recognized, its post-translational modifications, particularly acetylation, remain understudied in ischemia models. Investigating these modifications could have significant clinical implications for controlling c-Myc activity in the central nervous system. Although previous studies on c-Myc acetylation have been limited to non-neuronal cells, our research examines its expression in perifocal cells during stroke recovery to explore reg...
Source: NeuroMolecular Medicine - March 28, 2024 Category: Neurology Source Type: research
Probable Novel APP Met671Leu Mutation in a Chinese Han Family with Early-Onset Alzheimer ’s Disease
This study aimed to demonstrate a Chinese early-onset AD pedig ree presenting as progressive memory impairment, apraxia, visual-spatial disorders, psychobehavioral disorders, and personality changes with a novel APP gene mutation. The family contains four patients, three carries and three normal family members. The proband underwent brain magnetic resonance ima ging (MRI),18F-fludeoxyglucose positron emission tomography (18F-FDG-PET), cerebrospinal fluid amyloid detection,18F-florbetapir (AV-45) Positron Emission Computed Tomography (PET) imaging, whole-exome sequencing and Sanger sequencing. Brain MRI images showed brain ...
Source: NeuroMolecular Medicine - March 19, 2024 Category: Neurology Source Type: research
MiR206 and 423-3p Are Differently Modulated in Fast and Slow-Progressing Amyotrophic Lateral Sclerosis Patients
AbstractAmyotrophic lateral sclerosis (ALS) is a rare neuromuscular disease with a wide disease progression. Despite several efforts to develop efficient biomarkers, many concerns about the available ones still need to be addressed. MicroRNA (miR) are non-coding RNAs that can modulate molecular circuits and are involved in ALS pathogenic mechanisms. 22 fast and 23 slow-progressing-defined ALS patients were recruited. ALSFRS-R, strength, respiratory function, nerve conduction studies, and creatine kinase were evaluated at the baseline and after 6 months of follow-up. The mean monthly reduction of the previous variables (pro...
Source: NeuroMolecular Medicine - March 15, 2024 Category: Neurology Source Type: research
Effect of 2-Week Naringin Supplementation on Neurogenesis and BDNF Levels in Ischemia –Reperfusion Model of Rats
Conclusion: The results of the study show that 2 weeks of naringin supplementation may have protective effects on impaired neurogenesis and BDNF levels after brain ischemia and reperfusion in rats. (Source: NeuroMolecular Medicine)
Source: NeuroMolecular Medicine - March 8, 2024 Category: Neurology Source Type: research
Uncovering Sex-Specific Epigenetic Regulatory Mechanism Involving H3k9me2 in Neural Inflammation, Damage, and Recovery in the Internal Carotid Artery Occlusion Mouse Model
AbstractCerebral ischemic stroke is one of the foremost global causes of death and disability. Due to inadequate knowledge in its sequential disease mechanisms, therapeutic efforts to mitigate acute ischemia-induced brain injury are limited. Recent studies have implicated epigenetic mechanisms, mostly histone lysine acetylation/deacetylation, in ischemia-induced neural damage and death. However, the role of lysine methylation/demethylation, another prevalent epigenetic mechanism in cerebral ischemia has not undergone comprehensive investigation, except a few recent reports, including those from our research cohort. Conside...
Source: NeuroMolecular Medicine - February 26, 2024 Category: Neurology Source Type: research
Effects of Chronic Hypertension on the Energy Metabolism of Cerebral Cortex Mitochondria in Normotensive and in Spontaneously Hypertensive Rats During Aging
This study describes the effects of chronic hypertension on cerebral mitochondrial energy metabolism during aging through functional proteomics of enzymes at subcellular levels, i.e. in neuronal soma and synapses. In addition, this represents the starting point to envisage an experimental physiopathological model which could be useful also for pharmacological studies, to assess drug actions during the development of age-related pathologies that could coexist and/or are provoked by chronic hypertension.Graphical Abstract (Source: NeuroMolecular Medicine)
Source: NeuroMolecular Medicine - February 23, 2024 Category: Neurology Source Type: research
Amelioration of Astrocyte-Mediated Neuroinflammation by EI-16004 Confers Neuroprotection in an MPTP-induced Parkinson ’s Disease Model
AbstractParkinson ’s disease (PD) is a neurodegenerative disorder that results in motor impairment due to dopaminergic neuronal loss. The pathology of PD is closely associated with neuroinflammation, which can be characterized by astrocyte activation. Thus, targeting the inflammatory response in astrocytes might pr ovide a novel therapeutic approach. We conducted a luciferase assay on an in-house chemical library to identify compounds with anti-inflammatory effects capable of reducing MPP+-induced NF- κB activity in astrocytes. Among the compounds identified, EI-16004, a novel 3-benzyl-N-phenyl-1H-pyrazole-5-carboxamide...
Source: NeuroMolecular Medicine - January 30, 2024 Category: Neurology Source Type: research
Targeting Pericytes for Functional Recovery in Ischemic Stroke
AbstractPericytes surrounding endothelial cells in the capillaries are emerging as an attractive cell resource, which can show a large variety of functions in ischemic stroke, including preservation of the blood –brain barrier, regulation of immune function, and support for cerebral vasculature. These functions have been fully elucidated in previous studies. However, in recent years, increasing evidence has shown that pericytes play an important role in neurological recovery after ischemic stroke due to t heir regenerative function which can be summarized in two aspects according to current discoveries, one is that peric...
Source: NeuroMolecular Medicine - December 1, 2023 Category: Neurology Source Type: research
