PMID- 19570026 OWN - NLM STAT- MEDLINE DCOM- 20111207 LR - 20221229 IS - 1759-0914 (Electronic) IS - 1759-0914 (Linking) VI - 1 IP - 1 DP - 2009 Apr 14 TI - Regulated release of BDNF by cortical oligodendrocytes is mediated through metabotropic glutamate receptors and the PLC pathway. LID - 10.1042/AN20090006 [doi] LID - e00001 AB - A number of studies suggest that OLGs (oligodendrocytes), the myelinating cells of the central nervous system, are also a source of trophic molecules, such as neurotrophins that may influence survival of proximate neurons. What is less clear is how the release of these molecules may be regulated. The present study investigated the effects of BDNF (brain-derived neurotrophic factor) derived from cortical OLGs on proximate neurons, as well as regulatory mechanisms mediating BDNF release. Initial work determined that BDNF derived from cortical OLGs increased the numbers of VGLUT1 (vesicular glutamate transporter 1)-positive glutamatergic cortical neurons. Furthermore, glutamate acting through metabotropic, and not AMPA/kainate or NMDA (N-methyl-d-aspartate), receptors increased BDNF release. The PLC (phospholipase C) pathway is a key mediator of metabotropic actions to release BDNF in astrocytes and neurons. Treatment of OLGs with the PLC activator m-3M3FBS [N-(3-trifluoromethylphenyl)-2,4,6-trimethylbenzenesulfonamide] induced robust release of BDNF. Moreover, release elicited by the metabotropic receptor agonist ACPD [trans-(1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid] was inhibited by the PLC antagonist U73122, the IP3 (inositol triphosphate 3) receptor inhibitor 2-APB (2-aminoethoxydiphenylborane) and the intracellular calcium chelator BAPTA/AM [1,2-bis-(o-aminophenoxy)ethane-N,N,N',N'-tetra-acetic acid tetrakis(acetoxymethyl ester)]. Taken together, these results suggest that OLG lineage cells release BDNF, a molecule trophic for proximate neurons. BDNF release is regulated by glutamate acting through mGluRs (metabotropic glutamate receptors) and the PLC pathway. Thus glutamate and BDNF may be molecules that support neuron-OLG interactions in the cortex. FAU - Bagayogo, Issa P AU - Bagayogo IP AD - Department of Neuroscience and Cell Biology, University of Medicine and Dentistry of New Jersey/Robert Wood Johnson Medical School, 675 Hoes Lane, Piscataway, NJ 08854, USA. FAU - Dreyfus, Cheryl F AU - Dreyfus CF LA - eng GR - P01 HD023315/HD/NICHD NIH HHS/United States GR - R01 NS036647/NS/NINDS NIH HHS/United States PT - Comparative Study PT - Journal Article DEP - 20090414 PL - United States TA - ASN Neuro JT - ASN neuro JID - 101507115 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Receptors, Metabotropic Glutamate) RN - EC 3.1.4.- (Type C Phospholipases) SB - IM MH - Animals MH - Brain-Derived Neurotrophic Factor/*metabolism MH - Cells, Cultured MH - Cerebral Cortex/enzymology/*metabolism MH - Female MH - Oligodendroglia/enzymology/*metabolism MH - Pregnancy MH - Rats MH - Rats, Sprague-Dawley MH - Receptors, Metabotropic Glutamate/*physiology MH - Signal Transduction/*physiology MH - Type C Phospholipases/*physiology PMC - PMC2695578 EDAT- 2009/07/03 09:00 MHDA- 2011/12/13 00:00 PMCR- 2009/04/14 CRDT- 2009/07/03 09:00 PHST- 2009/07/03 09:00 [entrez] PHST- 2009/07/03 09:00 [pubmed] PHST- 2011/12/13 00:00 [medline] PHST- 2009/04/14 00:00 [pmc-release] AID - AN20090006 [pii] AID - e00001 [pii] AID - 10.1042/AN20090006 [doi] PST - epublish SO - ASN Neuro. 2009 Apr 14;1(1):e00001. doi: 10.1042/AN20090006.