Dexamethasone reverses adrenalectomy-induced neuronal de-differentiation in midbrain raphe-hippocampus axis.
Differentiation leads to specific morphological and biochemical characteristics. We examined whether epigenetic factors (e.g., glucocorticoids) are required to maintain neuronal differentiation in the adult brain. In the midbrain, adrenalectomy (ADX) (1-2 wk) reduced the size of tryptophan hydroxylase (WH)-immunoreactive (IR) neurons. ADX rats exposed to short-term (24-72-h) dexamethasone (ST-DEX) in the drinking saline (10 mg/l) showed an increase in WH protein, somal area and dendritic size of WH-IR neurons. In the hippocampus, ADX for 2-3 mo (long-term; LT) reduced Nissl staining, calbindin (CBD)-IR and 5-HT1A receptor mRNA in the granular cell layer, and the size of the molecular layer and its CBD-IR dendrites. Small vimentin (Vim)-IR glial cells emerged in the granular layer. ST-DEX after LT-ADX rapidly induced a recovery of 5-HT1A mRNA, Nissl labeling and CBD-IR in the granule cell layer. In the molecular layer, there was an increase in the area and in the number of CBD-IR dendrites. Furthermore, the Vim-IR glial cells were enlarged in size and branching. The rate of cell proliferation was studied in these animals. Immunostaining with antibodies against proliferating cell nuclear antigen (PCNA) and use of bromouridine argue against enhanced neurogenesis after ST-DEX in LT-ADX. We propose that glucocorticoids induce and maintain differentiation of serotonergic and CBD-IR neurons in the midbrain-hippocampal axis. A neuronotrophic role for the glial 5-HT1A receptor is suggested.
Azmitia
E C
EC
Department of Biology, New York University, New York 10003.
Liao
B
B
D000315:Adrenalectomy; D000818:Animals; D001933:Brain Stem / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D002454:Cell Differentiation; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D006624:Hippocampus / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D006801:Humans; D009473:Neuronal Plasticity; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D011903:Raphe Nuclei / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D009418:S100 Proteins / Q000032:analysis / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D014365:Tryptophan Hydroxylase / Q000032:analysis / Q000378:metabolism
D009418:S100 Proteins; D012701:Serotonin; D003907:Dexamethasone; D014365:Tryptophan Hydroxylase