Neuropharmacology, Journal Year: 2024, Volume and Issue: unknown, P. 110278 - 110278
Published: Dec. 1, 2024
Language: Английский
Cell Reports, Journal Year: 2024, Volume and Issue: 43(12), P. 115052 - 115052
Published: Dec. 1, 2024
Language: Английский
Citations
5
British Journal of Pharmacology, Journal Year: 2025, Volume and Issue: unknown
Published: April 21, 2025
Background and Purpose Nimodipine, an L‐type voltage‐gated calcium channel blocker, is approved cerebral vasorelaxant. We hypothesized that nimodipine attenuates the pro‐inflammatory shift in microglial phenotypes. Here, we analysed effects of on morphological functional phenotypes as well their transcriptomic profile. Experimental Approach Live brain slice preparations from C57BL/6 mice primary microglia cultures neonatal Sprague Dawley rats were used. Microglia activated either by ischemia or lipopolysaccharide (LPS), treated with (5–10–20 μM). Microglial phenotypes, phagocytic activity, Iba1 expression TNF‐α levels evaluated. Total RNA was isolated monocultures processed for next generation sequencing. Key Results LPS resulted a phenotype, affecting cytokines, complement system phagocytosis‐related genes. increased transcription ionotropic purinergic TRP channels but decreased voltage‐ ligand‐gated channels, down‐regulated Ryr IP 3 receptors SERCA pump. Nimodipine suppressed amoeboid transformation phagocytosis altered 110 genes opposite direction to activation, which at least 20 associated immune response, seven cell adhesion two autophagy regulation. Conclusion Implications The effect goes beyond vasorelaxation. activation modulating Ca 2+ ‐dependent gene involved intracellular signalling cascades drive responses. Consideration should be given expanding use
Language: Английский
Citations
0
Brain Sciences, Journal Year: 2025, Volume and Issue: 15(5), P. 442 - 442
Published: April 24, 2025
Background. Microglia, accounting for 5–15% of total brain cells, represent an essential population glial cells in the cultures used modeling neuroinflammation vitro. However, microglia proliferation is poor neuron–glial cultures. Here, we studied composition rat hippocampal cell prepared utilizing papain (PAP cultures) and trypsin (TRY as proteolytic enzymes isolation. Methods. To evaluate percentage morphology TRY PAP incubated presence TGFβ+MCSF+cholesterol, which should enhance proliferation, immunostaining calcium imaging approach combination with staining using recently developed vital fluorescent probe CDr20. Results. We have shown that was higher than Microglia are predominantly polarized, while bushy more characteristic also demonstrated TGFβ+MCSF+cholesterol increases number both (up to 25–30%) promotes appearance ameboid characterized by high mobility. significant observed already at early stages cultivation (2 DIV) cultures, described transformation 7 DIV. Based on absence ATP-induced Ca2+ response, round shape, mobility, suggested reactive. Conclusions. Thus, our results demonstrate a suitable enzyme preparing mixed heterogeneous functional neurons astrocytes (tricultures).
Language: Английский
Citations
0
bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown
Published: Nov. 12, 2024
Abstract Background Nimodipine, an L-type voltage-gated calcium channel blocker, achieves vasorelaxation by suppressing Ca 2+ -dependent activation of cerebrovascular smooth muscle cells and is used to prevent delayed ischemic deficit following subarachnoid hemorrhage. Our preclinical drug repurposing studies raised the possibility that nimodipine may attenuate pro-inflammatory shift in microglial function response brain injury. We analyzed effects on activated microglia at level morphological functional phenotypes, as well their transcriptomic profile. Methods Live slice preparations from C57BL/6 mice primary cultures cortex neonatal Sprague Dawley rats were used. Brain slices subjected ischemia, with lipopolysaccharide (LPS; 20 ng/ml). Both treated (5-10-20 μM). The degree arborization was evaluated Iba1-stained expressed a transformation index (TI). Phagocytic activity cultured visualized using fluorescent microbeads. TNFα levels measured ELISA. Total RNA isolated processed for next generation sequencing determine differentially genes. Results Nimodipine suppressed ameboid increased phagocytosis triggered ischemia LPS cultures. At transcriptional level, resulted phenotype, affecting expression cytokines, complement system phagocytosis-related Focusing role activation, transcription ionotropic purinergic some TRP channels but decreased voltage- ligand-gated channels. In endoplasmic reticulum, downregulated gene Ryr IP3 receptors SERCA pump gene. co-administered altered 110 genes opposite direction which least associated immune response, 7 cell adhesion 2 autophagy regulation. Conclusion effect goes beyond cerebral vasorelaxation. attenuates modulating involved intracellular signaling cascades drive responses. Consideration should be given expanding medical field indication nimodipine.
Language: Английский
Citations
1
Journal of Neurochemistry, Journal Year: 2024, Volume and Issue: 169(1)
Published: Dec. 18, 2024
The capacity of immune cells to alter their function based on metabolism is the basis emerging field immunometabolism. Microglia are resident innate central nervous system, and it a current focus investigate how alterations in impact these cells. have ability utilize lipids, such as fatty acids, energy sources, but also lipids can microglial form function. Recent studies highlighting different states transcriptional signatures highlighted modifications lipid processing defining states. This review highlights recent uses altered pathways discuss understanding biology microglia. here may phagocytic functioning or pro- anti-inflammatory balance. These provide foundation by which supplementation diet could influence Furthermore, targets modulating new treatment avenues.
Language: Английский
Citations
1
Molecular Neurodegeneration, Journal Year: 2024, Volume and Issue: 19(1)
Published: Dec. 18, 2024
Abstract Background The CD2-associated protein (CD2AP) was initially identified in peripheral immune cells and regulates cytoskeleton trafficking. Single nucleotide polymorphisms (SNPs) the CD2AP gene have been associated with Alzheimer’s disease (AD). However, functional role of CD2AP, especially its microglia during AD onset, remains elusive. Methods levels cultured primary 5xFAD mice studied. Microglial CD2AP-deficient were crossed offspring subjected to neuropathological assessment, behavioral tests, electrophysiology, RNA-seq, Golgi staining, biochemistry analysis. Primary also isolated for assessing their uptake morphology changes. Results We find that is abundantly expressed are elevated brain patients model at pathological stages. demonstrate haploinsufficiency significantly attenuates cognitive synaptic deficits, weakens response Aβ formation disease-associated (DAM), alleviates synapse loss mice. show exhibit compromised ability. In addition, we expression positively correlated complement C1q important phagocytosis DAM deposition. Moreover, reveal interacts colony stimulating factor 1 receptor (CSF1R) CSF1R cell surface levels, which may further affect expression. Conclusions Our results microgliosis identify a protective function microglial deficiency against deposition, suggesting importance detailed investigation AD-associated genes different thoroughly understanding exact contribution AD.
Language: Английский
Citations
0
Neuropharmacology, Journal Year: 2024, Volume and Issue: unknown, P. 110278 - 110278
Published: Dec. 1, 2024
Language: Английский
Citations
0