Neurotrophin secretion from cultured microglia

✍ Scribed by Kazuyuki Nakajima; Shizuyo Honda; Yoko Tohyama; Yoshinori Imai; Shinichi Kohsaka; Tadashi Kurihara

• Book ID: 102385232
• Publisher: John Wiley and Sons
• Year: 2001
• Tongue: English
• Weight: 253 KB
• Volume: 65
• Category: Article
• ISSN: 0360-4012
• DOI: 10.1002/jnr.1157

✦ Synopsis

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, PKCα 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 PKCα‐associated signal transduction mechanism. J. Neurosci. Res. 65:322–331, 2001. © 2001 Wiley‐Liss, Inc.