Dexamethasone reverses adrenalectomy-induced neuronal de-differentiation in midbrain raphe-hippocampus axis

E. C. Azmitia, B. Liao

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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.
Original languageUndefined
Pages (from-to)180-93; discussion 193-4, 221-2
JournalAnnals of the New York Academy of Sciences
StatePublished - 1994


  • *Adrenalectomy Animals Brain Stem/*cytology/drug effects/physiology Cell Differentiation Dexamethasone/*pharmacology Female Hippocampus/*cytology/drug effects/physiology Humans Neuronal Plasticity Neurons/*cytology/drug effects/physiology Raphe Nuclei/*cytology/drug effects/physiology S100 Proteins/analysis/metabolism Serotonin/metabolism Tryptophan Hydroxylase/analysis/metabolism

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