Single-Cell RNA Sequencing Transcriptomics Revealed HCMV IE2-Related Microglia Responses in Alzheimer ’s-Like Disease in Transgenic Mice
Abstract Although multiple factors are known to concur with Alzheimer’s disease (AD), the relationship between human cytomegalovirus (HCMV) and AD-like disease is unclear. Here, we propose a hypothesis that HCMV immediate-early 2 (IE2) protein promotes microglia activation and thus leads to AD-like disease. We successfully constructed IE2 transgenic mice expressing IE2 in the hippocampus. Single-cell sequencing analysis revealed that IE2 promoted the activation of microglia and upregulated the expression of disease-associated microglia genes. Differentially expressed gene analysis and pathway enrichment revealed t...
Source: Molecular Neurobiology - March 1, 2024 Category: Neurology Source Type: research
Optogenetic Approach in Trigeminal Neuralgia and Potential Concerns: Preclinical Insights
AbstractThe integration of optogenetics in the trigeminal pain circuitry broadens and reinforces existing pain investigations. Similar to research on spinal neuropathic pain, the exploration of the underlying determinants of orofacial pain is expanding. Optogenetics facilitates more direct, specific, and subtle investigations of the neuronal circuits involved in orofacial pain. One of the most significant concerns of both dentistry and medicine is trigeminal neuralgia (TN) management due to its substantial impact on a patient ’s quality of life. Our objective is to gather insights from preclinical studies conducted in TN...
Source: Molecular Neurobiology - March 1, 2024 Category: Neurology Source Type: research
Protective Effects of Plant-Derived Compounds Against Traumatic Brain Injury
AbstractInflammation in the nervous system is one of the key features of many neurodegenerative diseases. It is increasingly being identified as a critical pathophysiological primitive mechanism associated with chronic neurodegenerative diseases following traumatic brain injury (TBI). Phytochemicals have a wide range of clinical properties due to their antioxidant and anti-inflammatory effects. Currently, there are few drugs available for the treatment of neurodegenerative diseases other than symptomatic relief. Numerous studies have shown that plant-derived compounds, in particular polyphenols, protect against various neu...
Source: Molecular Neurobiology - March 1, 2024 Category: Neurology Source Type: research
Neuronal Stem Cells from Late-Onset Alzheimer Patients Show Altered Regulation of Sirtuin 1 Depending on Apolipoprotein E Indicating Disturbed Stem Cell Plasticity
AbstractLate-onset Alzheimer ’s disease (AD) is a complex multifactorial disease. The greatest known risk factor for late-onset AD is the E4 allele of the apolipoprotein E (APOE), while increasing age is the greatest known non-genetic risk factor. The cell type-specific functions of neural stem cells (NSCs), in particular the ir stem cell plasticity, remain poorly explored in the context of AD pathology. Here, we describe a new model that employs late-onset AD patient-derived induced pluripotent stem cells (iPSCs) to generate NSCs and to examine the role played by APOE4 in the expression of aging markers such as sirtuin ...
Source: Molecular Neurobiology - March 1, 2024 Category: Neurology Source Type: research
Screening for Differentially Expressed Memory Genes on a Diabetes Model Induced by High-Sugar Diet in Drosophila melanogaster: Potential Markers for Memory Deficits
AbstractType 2 diabetes mellitus (T2DM) has been shown to affect a series of cognitive processes including memory, increasing the risk for dementia, particularly Alzheimer ’s disease (AD). Although increasing evidence has supported that both diseases share common features, the pathophysiological mechanisms connecting these two disorders remain to be fully elucidated. Herein, we usedDrosophila melanogaster fed on a high-sugar diet (HSD) to mimic T2DM, and investigate its effects on memory as well as identify potential molecular players associated with the memory deficits induced by HSD. Flies hatched from and reared on HS...
Source: Molecular Neurobiology - March 1, 2024 Category: Neurology Source Type: research
The Role of Nicotine Metabolic Rate on Nicotine Dependence and Rewarding: Nicotine Metabolism in Chinese Male Smokers and Male Mice
AbstractThe exact relationship between nicotine metabolism and dependence is not fully understood but is known to be influenced at a molecular level by genetic factors. A sample comprising 274 Chinese adult male smokers was categorized into groups based on their metabolic rates, namely fast, intermediate, and slow metabolizers. We then measured their smoking topography, evaluated their nicotine dependence, and assessed the rewarding effects. Based on these findings, we proposed the hypothesis that the rate of nicotine metabolism could influence the level of dopamine release which in turn had repercussions on the pleasurabl...
Source: Molecular Neurobiology - March 1, 2024 Category: Neurology Source Type: research
Protective Effects of Plant-Derived Compounds Against Traumatic Brain Injury
AbstractInflammation in the nervous system is one of the key features of many neurodegenerative diseases. It is increasingly being identified as a critical pathophysiological primitive mechanism associated with chronic neurodegenerative diseases following traumatic brain injury (TBI). Phytochemicals have a wide range of clinical properties due to their antioxidant and anti-inflammatory effects. Currently, there are few drugs available for the treatment of neurodegenerative diseases other than symptomatic relief. Numerous studies have shown that plant-derived compounds, in particular polyphenols, protect against various neu...
Source: Molecular Neurobiology - March 1, 2024 Category: Neurology Source Type: research
RTA-408 Regulates p-NF- κB/TSLP/STAT5 Signaling to Ameliorate Nociceptive Hypersensitivity in Chronic Constriction Injury Rats
AbstractNeuropathic pain following nerve injury is a complex condition, which often puts a negative impact on life and remains a sustained problem. To make pain management better is of great significance and unmet need. RTA 408 (Omaveloxone) is a traditional Asian medicine with a valid anti-inflammatory property. Thus, we aim to investigate the therapeutic effect of RTA-408 on mechanical allodynia in chronic constriction injury (CCI) rats as well as the underlying mechanisms. Neuropathic pain was induced by using CCI of the rats ’ sciatic nerve (SN) and the behavior testing was measured by calibrated forceps testing. Act...
Source: Molecular Neurobiology - February 27, 2024 Category: Neurology Source Type: research
CCL2 Knockdown Attenuates Inflammatory Response After Spinal Cord Injury Through the PI3K/Akt Signaling Pathway: Bioinformatics Analysis and Experimental Validation
This study revealed that the inflammatory chemokine CCL2 can regulate the inflammatory response of PC-12 cells through the PI3K/Akt signaling pathway, and blocking the expression of the inflammatory chemokine CCL2 may be a promising strategy for the treatment of secondary injury after SCI. (Source: Molecular Neurobiology)
Source: Molecular Neurobiology - February 27, 2024 Category: Neurology Source Type: research
Let-7b-TLR7 Signaling Axis Contributes to the Anesthesia/Surgery-Induced Cognitive Impairment
AbstractPerioperative neurocognitive disorders (PNDs) are severe and common neurological complications among elderly patients following anesthesia and surgery. As the first line of defense of the innate immune system, Toll-like receptors (TLRs) have been found to be involved in the occurrence of neurodegenerative diseases in recent years. However, the role of TLR7 in the pathology and development of PNDs remains largely unclear. In our current study, we hypothesized that increased microRNA let-7b (let-7b) during anesthesia and surgical operation would activate TLR7 signaling pathways and mediate PNDs. Using a mouse model o...
Source: Molecular Neurobiology - February 27, 2024 Category: Neurology Source Type: research
The Emerging Role of Toll-Like Receptor-Mediated Neuroinflammatory Signals in Psychiatric Disorders and Acquired Epilepsy
AbstractThe new and evolving paradigms of psychiatric disorders pathogenesis are deeply inclined toward chronic inflammation that leads to disturbances in the neuronal networks of patients. A strong association has been established between the inflammation and neurobiology of depression which is mediated by different toll-like receptors (TLRs). TLRs and associated signalling pathways are identified as key immune regulators to stress and infections in neurobiology. They are a special class of transmembrane proteins, which are one of the broadly studied members of the Pattern Recognition Patterns family. This review focuses ...
Source: Molecular Neurobiology - February 27, 2024 Category: Neurology Source Type: research
Serum Uric Acid Levels and Outcome of Acute Ischemic Stroke: a Dose –Response Meta-analysis
AbstractPrevious meta-analyses have reported conflicting results regarding the relationship between baseline uric acid (UA) levels and acute ischemic stroke (AIS) outcomes. Therefore, we conducted a dose –response meta-analysis to elucidate the association’s strength and shape. Studies on the association between baseline UA levels and AIS outcomes in the PubMed and EMBASE databases were searched from their inception to April 17, 2023. Two researchers independently reviewed the studies for inclus ion. A total of 23 articles involving 15,733 patients with AIS were included. The analysis revealed a significant inverse cor...
Source: Molecular Neurobiology - February 27, 2024 Category: Neurology Source Type: research
Hypoxia-Induced miR-101 Impairs Endothelial Barrier Integrity Through Altering VE-Cadherin and Claudin-5
This study aims to investigate the role of miRNA in hypoxia-induced endothelial barrier disruption. In this study, brain en dothelial cells were exposed to hypoxic conditions for different time points. Western blotting, overexpression and knockdown of miRNA, real-time PCR, TEER, and sodium fluorescein assay were used to examine the effect of hypoxic conditions on brain endothelial cells. Hypoxic exposure was validated us ing HIF-1α protein. Exposure to hypoxic conditions resulted to a significant decrease in endothelial barrier resistance and an increase in sodium fluorescein migration across the endothelial barrier. Redu...
Source: Molecular Neurobiology - February 27, 2024 Category: Neurology Source Type: research
FKBP51-Hsp90 Interaction-Deficient Mice Exhibit Altered Endocrine Stress Response and Sex Differences Under High-Fat Diet
AbstractFK506-binding protein 51 kDa (FKBP51), encoded byFkbp5 gene, gained considerable attention as an important regulator of several aspects of human biology including stress response, metabolic dysfunction, inflammation, and age-dependent neurodegeneration. Its catalytic peptidyl-prolyl isomerase (PPIase) activity is mediated by the N-terminal FK506-binding (FK1) domain, whereas the C-terminal tetratricopeptide motif (TPR) domain is responsible for FKBP51 interaction with molecular chaperone heat shock protein 90 (Hsp90). To understand FKBP51-related biology, several mouse models have been created. These includeFkbp5...
Source: Molecular Neurobiology - February 27, 2024 Category: Neurology Source Type: research
Quantitative Proteomic and Phosphoproteomic Analyses Reveal a Role of Death-Associated Protein Kinase 1 in Regulating Hippocampal Synapse
AbstractDeath-associated protein kinase 1 (DAPK1) is a stress-responsive calcium/calmodulin (CaM)-regulated serine/threonine protein kinase that is actively involved in stress-induced cell death. The dysregulation of DAPK1 has been established in various neurological disorders such as epilepsy, Alzheimer ’s disease (AD), and Parkinson’s disease (PD). Recent research indicates a synaptic localization of DAPK1 in neurons, suggesting a potential role of DAPK1 in modulating synaptic structure and function. However, the key molecules and pathways underlying the influence of DAPK1 on synapses remain e lusive. We utilized qua...
Source: Molecular Neurobiology - February 27, 2024 Category: Neurology Source Type: research
