COP-22 Alleviates d-Galactose –Induced Brain Aging by Attenuating Oxidative Stress, Inflammation, and Apoptosis in Mice
In this study, COP-22, a mono-carbonyl curcumin derivative, was evaluated for its anti-aging ability, especially its ability to resist brain aging induced byD-galactose (D-gal) in mice. For brain protection, COP-22 could resist D-gal –induced oxidative stress by increasing the activity of antioxidative defense enzymes and enhancing antioxidant capacity in the brain tissue; COP-22 could improve the dysfunction of the cholinergic system by decreasing the increased activity of acetylcholinesterase and increasing the reduced conte nt of acetylcholine induced by D-gal; and COP-22 could protect nerve cells of the brain. Furthe...
Source: Molecular Neurobiology - February 12, 2024 Category: Neurology Source Type: research
The Inflammation/NF- κB and BDNF/TrkB/CREB Pathways in the Cerebellum Are Implicated in the Changes in Spatial Working Memory After Both Morphine Dependence and Withdrawal in Rat
AbstractWe aimed to explore the impact of the cerebellum on the decline in spatial working memory following morphine dependence and withdrawal. Two groups of male Wistar rats received intraperitoneal injections of either saline (1 ml/kg) or morphine (10 mg/kg) twice daily for 10 days, serving as the control and dependent groups. Additionally, a withdrawal group underwent a 30-day withdrawal period after the dependence phase. Spatial working memory was assessed using a Y maze test. ELISA and western blot were used to asses s protein levels in the cerebellum. On day 1, morphine impaired spatial working memory, deteriorat...
Source: Molecular Neurobiology - February 12, 2024 Category: Neurology Source Type: research
Contribution of ApoB-100/SORT1-Mediated Immune Microenvironment in Regulating Oxidative Stress, Inflammation, and Ferroptosis After Spinal Cord Injury
This study aims to explore the impacts of ApoB-100/SORT1-mediated immune microenvironment during acute spinal cord injury (SCI), and to investigate the potential mechanism. CB57BL/6 mice underwent moderate thoracic contusion injury to establish the SCI animal model, and received ApoB-100 lentivirus injection to interfere ApoB-100 level. Functional recovery was assessed using the Basso, Beattie, and Bresnahan (BBB) score and footprint analysis. Transmission electron microscopy was applied to observe the ultrastructure of the injured spinal cord tissue. Hematoxylin-eosin (HE) staining and Perls staining were conducted to ass...
Source: Molecular Neurobiology - February 10, 2024 Category: Neurology Source Type: research
Emerging Functional Connections Between Metabolism and Epigenetic Remodeling in Neural Differentiation
AbstractStem cells possess extraordinary capacities for self-renewal and differentiation, making them highly valuable in regenerative medicine. Among these, neural stem cells (NSCs) play a fundamental role in neural development and repair processes. NSC characteristics and fate are intricately regulated by the microenvironment and intracellular signaling. Interestingly, metabolism plays a pivotal role in orchestrating the epigenome dynamics during neural differentiation, facilitating the transition from undifferentiated NSC to specialized neuronal and glial cell types. This intricate interplay between metabolism and the ep...
Source: Molecular Neurobiology - February 10, 2024 Category: Neurology Source Type: research
USP18 Stabilized FTO Protein to Activate Mitophagy in Ischemic Stroke Through Repressing m6A Modification of SIRT6
AbstractIschemic stroke (IS) is a dangerous cerebrovascular disorder with a significant incidence and death rate. Ubiquitin-specific peptidase 18 (USP18) has been proven to mitigate ischemic brain damage; however, its potential regulatory mechanisms remain unclear. In vivo and in vitro models of IS were established by middle cerebral artery occlusion (MCAO) and oxygen –glucose deprivation/reoxygenation (OGD/R). Neurocyte injury was detected by MTT, LDH, ROS level, mitochondrial membrane potential (Δψm), and flow cytometry. Molecular expression was evaluated by qPCR, Western blotting, and immunofluorescence staining. Mo...
Source: Molecular Neurobiology - February 10, 2024 Category: Neurology Source Type: research
Shaping the Neurovascular Unit Exploiting Human Brain Organoids
AbstractBrain organoids, three-dimensional cell structures derived from pluripotent stem cells, closely mimic key aspects of the human brainin vitro, providing a powerful tool for studying neurodevelopment and disease. The neuroectodermal induction protocol employed for brain organoid generation primarily gives rise to the neural cellular component but lacks the vital vascular system, which is crucial for the brain functions by regulating differentiation, migration, and circuit formation, as well as delivering oxygen and nutrients. Many neurological diseases are caused by dysfunctions of cerebral microcirculation, making v...
Source: Molecular Neurobiology - February 9, 2024 Category: Neurology Source Type: research
Electroacupuncture Alleviates Hyperalgesia and Anxiety-Like Behaviors in Pain Memory Model Rats Through Activation of GABAergic Neurons and GABA Receptor in the Rostral Anterior Cingulate Cortex
This study revealed that the effect of EA on pain memory-induced negative behaviors is related to the mediation of GABAergic neuron activity and GABA receptor expression in the rostral anterior cingulate cortex (rACC). Previous studies have shown that the rACC is a crucial area for regulating nociceptive behaviors and negative emotions in pain memory models. The GABAergic neurons and receptors in the rACC are largely involved in pain sensation and related effects. However, the relationships among pain memory, GABAergic neurons and receptors in the rACC have not been investigated. In this study, we established a pain memory...
Source: Molecular Neurobiology - February 8, 2024 Category: Neurology Source Type: research
Restoration of nNOS Expression Rescues Autistic-Like Phenotypes Through Normalization of AMPA Receptor-Mediated Neurotransmission
AbstractAutism spectrum disorder (ASD) is associated with a range of abnormalities characterized by deficits in socialization, communication, repetitive behaviors, and restricted interests. We have recently shown that neuronal nitric oxide synthase (nNOS) expression was decreased in the basolateral amygdala (BLA) of mice after postnatal valproic acid exposure. Neuronal activity-regulated pentraxin (Narp) could contribute to the regulation of the GluA4 2-amino-3-(5-methyl-3-oxo-1,2-oxazol-4-yl) propanoic acid (AMPA) subunits which are predominantly expressed in interneurons. However, the specific role of nNOS re-expression ...
Source: Molecular Neurobiology - February 8, 2024 Category: Neurology Source Type: research
Identification of Autophagy-Related Candidate Genes in the Early Diagnosis of Alzheimer ’s Disease and Exploration of Potential Molecular Mechanisms
This study aimed to identify autophagy-related candidate genes for the early diagnosis of Alzheimer ’s disease (AD) and elucidate their potential molecular mechanisms. Differentially expressed genes (DEGs) and phenotype-associated significant module genes were obtained using the “limma” package and weighted gene co-expression network analysis (WGCNA) based on hippocampal tissue datasets from AD patients and control samples. The intersection between the list of autophagy-related genes (ATGs), DEGs, and module genes was further investigated to obtain AD-autophagy-related differential expression genes (ATDEGs). Subseque...
Source: Molecular Neurobiology - February 8, 2024 Category: Neurology Source Type: research
Quercetin Ameliorates Cognitive Impairment in Depression by Targeting HSP90 to Inhibit NLRP3 Inflammasome Activation
AbstractCognitive dysfunction was a common symptom of major depressive disorder (MDD). In previous studies, psychological stress leads to activation and proliferation of microglial cells in different brain regions. Quercetin, a bioflavonoid derived from vegetables and fruits, exerts anti-inflammatory effects in various diseases. To demonstrate the role of quercetin in the hippocampal inflammatory response in depress mice. The chronic unpredictable stress (CUS) depressive mice model built is used to explore the protective effects of quercetin on depression. Neurobehavioral test, protein expression of NOD-like receptor the...
Source: Molecular Neurobiology - February 8, 2024 Category: Neurology Source Type: research
Desmoglein-2 Affects Vascular Function in Moyamoya Disease by Interacting with MMP-9 and Influencing PI3K Signaling
This study aimed to investigate the effect of desmoglein-2 (DSG2) on Moyamoya disease and determine the inhibitory effect of DSG2 in vascular remodeling in Moyamoya disease.RNA sequencing, immunohistochemistry (IHC), and western blotting were used to detect the expression of DSG2 in the superficial temporal artery (STA) tissues of Moyamoya disease. The association between DSG2 and endothelial cells ’ biological activities was investigated by cell counting kit-8 (CCK-8), migration assay, tube formation assay, flow cytometry with Annexin V-FITC/PI staining, and TUNEL apoptotic cell detection kit. Pathways affected by overe...
Source: Molecular Neurobiology - February 7, 2024 Category: Neurology Source Type: research
Discovery and Exploration of Lipid-Modifying Drug Targets for ALS by Mendelian Randomization
AbstractObservational studies have faced challenges in identifying replicable causes for amyotrophic lateral sclerosis (ALS). To address this, we employed an unbiased and data-driven approach to discover and explore potential causal exposures using two-sample Mendelian randomization (MR) analyses. In the phenotype discovery stage, we assessed 3948 environmental exposures from the UK Biobank and utilized ALS summary statistics (Europeans, 20,806 cases, 59,804 controls) as the outcome within a phenome-wide MR pipeline. Through a range of sensitivity analyses, two medication traits were identified to be protective for ALS. In...
Source: Molecular Neurobiology - February 7, 2024 Category: Neurology Source Type: research
Exosomal circZNF800 Derived from Glioma Stem-like Cells Regulates Glioblastoma Tumorigenicity via the PIEZO1/Akt Axis
This study focuses on the molecular mechanism by which circRNAs from glioma stem-like cell (GSLC) exosomes regulate glioblastoma (GBM) tumorigenicity. In this study, we validated that GSLC exosomes accelerated the malignant phenotype of GBM. Subsequently, we found that circZNF800 was highly expressed in GSLC exosomes and was negatively associated with GBM patients. CircZNF800 promoted GBM cell proliferation and migration and inhibited GBM cell apoptosis in vitro. Silencing circZNF800 could improve the GBM xenograft model survival rate. Mechanistic studies revealed that circZNF800 activated the PIEZO1/Akt signaling pathway ...
Source: Molecular Neurobiology - February 7, 2024 Category: Neurology Source Type: research
Remote Ischemia Postconditioning Mitigates Hippocampal Neuron Impairment by Modulating Cav1.2-CaMKII α-Aromatase Signaling After Global Cerebral Ischemia in Ovariectomized Rats
AbstractBrain-derived estrogen (BDE2) is gaining attention as an endogenous neurotransmitter. Recent research has revealed that selectively removing the aromatase gene, the pivotal enzyme responsible for BDE2 synthesis, in forebrain neurons or astrocytes can lead to synaptic loss and cognitive impairment. It is worth noting that remote ischemia post-conditioning (RIP), a non-invasive technique, has been shown to activate natural protective mechanisms against severe ischemic events. The aim of our study was to investigate whether RIP triggers aromatase-BDE2 signaling, shedding light on its neuroprotective mechanisms after g...
Source: Molecular Neurobiology - February 6, 2024 Category: Neurology Source Type: research
Mitochondria-Endoplasmic Reticulum Contact Sites (MERCS): A New Axis in Neuronal Degeneration and Regeneration
AbstractMitochondria-Endoplasmic Reticulum Contact Sites (MERCS) are dynamic structures whose physiological interaction is vital to direct life and death of the cell. A bevy of tethering proteins, mitofusin-1/2 (Mfn-1/2), glucose-regulated protein-75 (Grp-75), voltage-dependent anion channel-1 (VDAC1), and dynamic-related protein-1 (Drp1), plays an integral role in establishing and regulating this intricate intracellular communication. Dysregulation of this interplay leads to various neurodegenerative disorders, like Alzheimer ’s disease (AD), Parkinson’s disease (PD), stroke, traumatic brain injury (TBI), amyotrophic ...
Source: Molecular Neurobiology - February 6, 2024 Category: Neurology Source Type: research
