We studied the involvement of cAMP and PKA in the regulation of the secretion of neurotrophic growth factors by macro-and microglial cells in the model of ethanol-induced neurodegeneration in vitro and in vivo. The stimulating role of cAMP in the secretion of neurotrophins by intact astrocytes and oligodendrocytes was shown, while PKA does not participate in this process. On the contrary, the inhibitory role of cAMP (implemented via PKA activation) in the production of neurogenesis stimulators by microglial cells under conditions of optimal vital activity was found. Under the influence of ethanol, the role of cAMP and PKA in the production of growth factors by macroglial cells was considerably changed. The involvement of PKA in the cAMP-dependent signaling pathways and inversion of the role of this signaling pathway in the implementation of the neurotrophic secretory function of astrocytes and oligodendrocytes, respectively, directly exposed to ethanol in vitro were noted. Long-term exposure of the nervous tissue to ethanol in vivo led to the loss of the stimulating role of cAMP/PKA signaling on neurotrophin secretion by macroglial cells without affecting its inhibitory role in the regulation of this function in microglial cells.
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http://dx.doi.org/10.1007/s10517-023-05800-7 | DOI Listing |
Metab Brain Dis
January 2025
Department of Neurology, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR, 97239, USA.
Neuroinflammation and mitochondrial dysfunction are early events in Alzheimer's disease (AD) and contribute to neurodegeneration and cognitive impairment. Evidence suggests that the inflammatory axis mediated by macrophage migration inhibitory factor (MIF) binding to its receptor, CD74, plays an important role in many central nervous system (CNS) disorders such as AD. Our group has developed DRhQ, a novel CD74 binding construct which competitively inhibits MIF binding, blocks macrophage activation and migration into the CNS, enhances anti-inflammatory microglia cell numbers and reduces pro-inflammatory gene expression.
View Article and Find Full Text PDFActa Pharm Sin B
December 2024
Department of Translational Neuroscience, Jing'an District Centre Hospital of Shanghai, Institutes of Brain Science, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai 200032, China.
Spinal microglia and astrocytes are both involved in neuropathic and inflammatory pain, which may display sexual dimorphism. Here, we demonstrate that the sustained activation of spinal astrocytes and astrocyte-derived interleukin (IL)-17A promotes the progression of mouse bone cancer pain without sex differences. Chemogenetic or pharmacological inhibition of spinal astrocytes effectively ameliorates bone cancer-induced pain-like behaviors.
View Article and Find Full Text PDFJ Tradit Complement Med
January 2025
National Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taipei City, 112026, Taiwan.
Amidst growing concerns over COVID-19 aftereffects like fatigue and cognitive issues, NRICM101, a traditional Chinese medicine, has shown promise. Used by over 2 million people globally, it notably reduces hospitalizations and intubations in COVID-19 patients. To explore whether NRICM101 could combat COVID-19 brain fog, we tested NRICM101 on hACE2 transgenic mice administered the S1 protein of SARS-CoV-2, aiming to mitigate S1-induced cognitive issues by measuring animal behaviors, immunohistochemistry (IHC) staining, and next-generation sequencing (NGS) analysis.
View Article and Find Full Text PDFJ Tradit Complement Med
January 2025
Institute of Food Science and Technology, College of Bioresources and Agriculture, National Taiwan University, Taipei, Taiwan.
Background And Aim: (CM) and (AM) are medicinal mushrooms with potential applications in the treatment of mood disorders, including depression and anxiety. While research suggests that both CM and AM possess anti-inflammatory properties and hold potential for treating depression when administered separately, there is limited knowledge about their efficacy when combined in a formula, as well as the underlying mechanism involving the modulation of microglia.
Experimental Procedure: Rats received oral administrations of the low-dose formulation, medium-dose formulation, and high-dose formulation over 28 consecutive days as part of the UCMS protocols.
Korean J Physiol Pharmacol
January 2025
Department of Pharmacology, Catholic Kwandong University College of Medicine, Gangneung 25601, Korea.
Neurosteroids play an important role as endogenous neuromodulators that are locally produced in the central nervous system and rapidly change the excitability of neurons and the activation of microglial cells and astrocytes. Here we review the mechanisms of synthesis, metabolism, and actions of neurosteroids in the central nervous system. Neurosteroids are able to play a variety of roles in the central nervous system under physiological conditions by binding to membrane ion channels and receptors such as gamma-aminobutyric acid type A receptors, Nmethyl- D-aspartate receptors, L- and T-type calcium channels, and sigma-1 receptors.
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