Journal
EUROPEAN JOURNAL OF NEUROSCIENCE
Volume 27, Issue 6, Pages 1320-1332Publisher
BLACKWELL PUBLISHING
DOI: 10.1111/j.1460-9568.2008.06104.x
Keywords
agmatine; arginine decarboxylase; hippocampus; prefrontal cortex; repeated restraint stress; beta-tubulin III
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Funding
- NCRR NIH HHS [P20 RR017701, P20 RR017701-076628, RR17701, P20 RR017701-076630] Funding Source: Medline
- NIMH NIH HHS [K02 MH002031, MH02031, K02 MH002031-06] Funding Source: Medline
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Agmatine is an endogenous amine derived from decarboxylation of arginine catalysed by arginine decarboxylase. Agmatine is considered a novel neuromodulator and possesses neuroprotective properties in the central nervous system. The present study examined whether agmatine has neuroprotective effects against repeated restraint stress-induced morphological changes in rat medial prefrontal cortex and hippocampus. Sprague-Dawley rats were subjected to 6 h of restraint stress daily for 21 days. Immunohistochemical staining with beta-tubulin III showed that repeated restraint stress caused marked morphological alterations in the medial prefrontal cortex and hippocampus. Stress-induced alterations were prevented by simultaneous treatment with agmatine (50 mg/kg/day, i.p.). Interestingly, endogenous agmatine levels, as measured by high-performance liquid chromatography, in the prefrontal cortex and hippocampus as well as in the striatum and hypothalamus of repeated restraint rats were significantly reduced as compared with the controls. Reduced endogenous agmatine levels in repeated restraint animals were accompanied by a significant increase of arginine decarboxylase protein levels in the same regions. Moreover, administration of exogenous agmatine to restrained rats abolished increases of arginine decarboxylase protein levels. Taken together, these results demonstrate that exogenously administered agmatine has neuroprotective effects against repeated restraint-induced structural changes in the medial prefrontal cortex and hippocampus. These findings indicate that stress-induced reductions in endogenous agmatine levels in the rat brain may play a permissive role in neuronal pathology induced by repeated restraint stress.
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