Induction of microglial apoptosis by corticotropin-releasing hormone.
Neuropeptides are short-chain peptides found in brain tissue, some of which function as neurotransmitters and others as hormones. Neuropeptides may directly or indirectly modulate glial functions in the CNS. In the present study, effects of various neuropeptides on the viability and inflammatory activation of cultured microglia were investigated. Vasoactive intestinal peptide, substance P, cholecystokinin and neuropeptide Y did not affect microglial cell viability, whereas corticotropin-releasing hormone (CRH) induced a classical apoptosis of mouse microglia in culture as shown by nuclear condensation and fragmentation, terminal deoxynucleotidyl transferase dUTP nick-end labeling, and cleavage of caspase 3 and poly(ADP-ribose) polymerase protein. CRH, however, did not influence nitric oxide production or expression of inflammatory genes including those encoding cytokines and chemokines, indicating that CRH did not affect the inflammatory activation of microglia. The CRH-induced microglial apoptosis appeared to involve a mitochondrial pathway and reactive oxygen species, based on the mitochondrial membrane potential change, caspase 9 activation and sensitivity to antioxidants. Taken together, our results indicate that the stress neuropeptide CRH may regulate neuroinflammation by inducing the apoptosis of microglia, the major cellular source of inflammatory mediators in the CNS.
Ock
Jiyeon
J
Department of Pharmacology, Kyungpook National University School of Medicine, Daegu, Korea.
Lee
Heasuk
H
Kim
Sangseop
S
Lee
Won-Ha
WH
Choi
Dong-Kug
DK
Park
Eun Jung
EJ
Kim
Sang-Hyun
SH
Kim
In Kyeom
IK
Suk
Kyoungho
K
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D002470:Cell Survival / Q000502:physiology; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology / Q000502:physiology*; D018836:Inflammation Mediators / Q000494:pharmacology / Q000502:physiology; D051379:Mice; D017628:Microglia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D009479:Neuropeptides / Q000494:pharmacology / Q000502:physiology
D018836:Inflammation Mediators; D009479:Neuropeptides; D003346:Corticotropin-Releasing Hormone