title: Repeated immobilization stress alters rat hippocampal and prefrontal cortical morphology in parallel with endogenous agmatine and arginine decarboxylase levels.
abstract: Agmatine, an endogenous amine derived from decarboxylation of L-arginine catalyzed by arginine decarboxylase, has been proposed as a neurotransmitter or neuromodulator in the brain. In the present study, we examined whether agmatine has neuroprotective effects against repeated immobilization-induced morphological changes in brain tissues and possible effects of immobilization stress on endogenous agmatine levels and arginine decarboxylase expression in rat brains. Sprague-Dawley rats were subjected to 2h immobilization stress daily for 7 days. This paradigm significantly increased plasma corticosterone levels, and the glutamate efflux in the hippocampus as measured by in vivo microdialysis. Immunohistochemical staining with beta-tubulin III showed that repeated immobilization caused marked morphological alterations in the hippocampus and medial prefrontal cortex that were prevented by simultaneous treatment with agmatine (50mg/kg/day), i.p.). Likewise, endogenous agmatine levels measured by high-performance liquid chromatography in the prefrontal cortex, hippocampus, striatum and hypothalamus were significantly increased by immobilization, as compared to controls. The increased endogenous agmatine levels, ranging from 92 to 265% of controls, were accompanied by a significant increase of arginine decarboxylase protein levels in the same regions. These results demonstrate that the administration of exogenous agmatine protects the hippocampus and medial prefrontal cortex against neuronal insults caused by repeated immobilization. The parallel increase in endogenous brain agmatine and arginine decarboxylase protein levels triggered by repeated immobilization indicates that the endogenous agmatine system may play an important role in adaptation to stress as a potential neuronal self-protection mechanism.
authors.affiliation: Department of Pharmacology, Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37604, USA. zhum@etsu.edu
authors.forename: Meng-Yang
authors.initials: MY
authors.lastname: Zhu
authors.forename: Wei-Ping
authors.initials: WP
authors.lastname: Wang
authors.forename: Jingjing
authors.initials: J
authors.lastname: Huang
authors.forename: Yang-Zheng
authors.initials: YZ
authors.lastname: Feng
authors.forename: Soundar
authors.initials: S
authors.lastname: Regunathan
authors.forename: Garth
authors.initials: G
authors.lastname: Bissette
mesh_terms: D000376:Agmatine / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D002262:Carboxy-Lyases / Q000378:metabolism*; D003345:Corticosterone / Q000097:blood; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D009410:Nerve Degeneration / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D018696:Neuroprotective Agents / Q000378:metabolism / Q000494:pharmacology; D017397:Prefrontal Cortex / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012149:Restraint, Physical; D013315:Stress, Psychological / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D014404:Tubulin / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology
chemical_list: D018696:Neuroprotective Agents; D014404:Tubulin; D018698:Glutamic Acid; D000376:Agmatine; D002262:Carboxy-Lyases; C019722:arginine decarboxylase; D003345:Corticosterone