Neurotrophin secretion from cultured microglia

Abstract

Because microglia have been suggested to produce neurotrophins, we tested this ability in vitro. Rat primary microglia were found to constitutively secrete a limited amount of brain-derived neurotrophic factor (BDNF), but nerve growth factor (NGF) and neurotrophin-3 (NT-3) were undetectable in the conditioned medium. Stimulation of the cells with lipopolysaccharide (LPS) increased BDNF secretion, and induced NGF secretion. As a first step to examine this regulation system, the association of protein kinase C (PKC) was pharmacologically analyzed. A PKC activator, phorbol-12-myristate-13-acetate, enhanced the secretion of BDNF. Pre-treatment of microglia with a PKC inhibitor, bisindolylmaleimide, suppressed LPS-stimulated BDNF secretion as well as the constitutive one. These results suggest that the PKC signaling cascade is closely associated with BDNF secretion. Among PKC isoforms, PKCalpha probably plays a role in BDNF secretion, based on the results of experiments using a specific PKC activator, 1-oleoyl-2-acetyl-sn-glycerol, and a specific PKC inhibitor, Gö 6976, and by immunoblotting. Taken together, these findings suggest that the secretion of BDNF from microglia is regulated through PKCalpha-associated signal transduction mechanism.

GM1 induces p38 and microtubule dependent ramification of rat primary microglia in vitro

“…Neurotrophins are a family of structurally and functionally related molecules, including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), NT-3, and NT-4/5. Neurotrophins have been shown to induce morphological changes and differentiation in neurons (Barbacid, 1994(Barbacid, , 1995Chao and Hempstead, 1995), they are released from microglia and regulate proliferation and morphological changes by autocrine-or paracrine-manner (Nakajima et al, 2001;Zhang et al, 2003). These earlier observations together with our present findings led us to suggest that Gmix may induce the release of neurotrophins from rat primary microglia and the released neurotrophins may then induce their ramified morphological changes.…”

Macrophages and HIV-1: dangerous liaisons

“…These molecules interact closely with inflammatory factors. For example, IL-1, TNF- and LPS induce or increase the expression of the nerve growth factor (NGF) by microglia through a NFB-dependent mechanism (Heese et al, 1998a;Heese et al, 1998b;Lindholm et al, 1987;Mallat et al, 1989;Nakajima et al, 2001), whereas the complement component C3a has the same effect independently of NFB activation (Heese et al, 1998b).…”

“…Likewise, LPS and C8 ceramide induce microglia to release brain-derived neutrophic factor (BDNF), the latter acting even in the absence of tumour necrosis factor  (TNF- (Nakajima et al, 2001;Nakajima et al, 2002). Interleukin-1 (IL-1 is a key regulator of ciliary neurotrophic factor (CNTF) production by astrocytes (Herx et al, 2000).…”

Neonatal vaccination with bacille Calmette-Guérin promotes the dendritic development of hippocampal neurons

“…The interplay of cytokines and neurotrophins is complex. Neural traffic factors can be secreted by several types of immune cells, including T cells, microglia, macrophages and mast cells, 50,51 particularly after exposing these cells to various cytokines, including TNF-a, IL-1b and IL-6. 52,53 Once secreted, these neurotrophins can serve as mediators of the beneficial effects of immunity on neural development.…”