Nerve growth factor promotes differentiation and protects the oligodendrocyte precursor cells from in vitro hypoxia/ischemia

Abstract

IntroductionNerve growth factor (NGF) is a pleiotropic molecule acting on different cell types in physiological and pathological conditions. However, the effect of NGF on the survival, differentiation and maturation of oligodendrocyte precursor cells (OPCs) and oligodendrocytes (OLs), the cells responsible for myelin formation, turnover, and repair in the central nervous system (CNS), is still poorly understood and heavily debated.MethodsHere we used mixed neural stem cell (NSC)-derived OPC/astrocyte cultures to clarify the role of NGF throughout the entire process of OL differentiation and investigate its putative role in OPC protection under pathological conditions.ResultsWe first showed that the gene expression of all the neurotrophin receptors (TrkA, TrkB, TrkC, and p75NTR) dynamically changes during the differentiation. However, only TrkA and p75NTR expression depends on T3-differentiation induction, as Ngf gene expression induction and protein secretion in the culture medium. Moreover, in the mixed culture, astrocytes are the main producer of NGF protein, and OPCs express both TrkA and p75NTR. NGF treatment increases the percentage of mature OLs, while NGF blocking by neutralizing antibody and TRKA antagonist impairs OPC differentiation. Moreover, both NGF exposure and astrocyte-conditioned medium protect OPCs exposed to oxygenglucose deprivation (OGD) from cell death and NGF induces an increase of AKT/pAKT levels in OPCs nuclei by TRKA activation.DiscussionThis study demonstrated that NGF is implicated in OPC differentiation, maturation, and protection in the presence of metabolic challenges, also suggesting implications for the treatment of demyelinating lesions and diseases.

MicroRNAs dysregulated in multiple sclerosis affect the differentiation of CG-4 cells, an oligodendrocyte progenitor cell line

“…It is, therefore, not clear which pathway supports their proliferation. This should be further explored as, for example, Jun N-terminal kinase (Jnk) interacting protein 1 [also called mitogen-activated protein kinase 8 interacting protein 1 ( Mapk8ip1 )] and Jun , elements of the Jnk signaling pathway involved in OPC proliferation, were slightly but significantly upregulated, as well as Ntrk3 , that has been linked to both OPC proliferation/survival and differentiation (data not shown) ( Kumar et al, 1998 ; Chew et al, 2010 ; Baldassarro et al, 2023 ). However, miR-34c-5p was also identified as anti-proliferative in glioblastoma and osteosarcoma cells ( Wu et al, 2013 ; Wang Y. et al, 2019 ).…”

NGF contributes to activities of acid‐sensing ion channels in dorsal root ganglion neurons of male rats with experimental peripheral artery disease

“…The new findings are presented in Figure 4. That is, Figure 4a shows that the pretreatment of 1 μM GW441756, an inhibitor of TrkA for 4 h (Baldassarro et al, 2023;Terada et al, 2018), significantly decreased amplification of ASIC3-like currents induced by preapplication of 100 ng/mL NGF for 24 h in the control group (p = 0.0347 between GW441756 + NGF/n = 26 and NGF/n = 28). Note that the pretreatment of 1 μM GW441756 did not alter ASIC1a current density in L4-6 DRG neurons of all the groups.…”

Nerve Growth Factor and the Role of Inflammation in Tumor Development

“…NGF is synthesized as a precursor, called pro-NGF, which after processing generates the mature NGF molecule. NGF is primarily produced by various cell types, including immune cells, endothelial cells, and tissues within the nervous system [14,[26][27][28].…”