Controversies surrounding glucocorticoid-mediated cell death in the hippocampus.
The adrenal gland releases mineralocorticoids (MCs) and glucocorticoids (GCs) in response to a variety of stimuli, including stress. Once released, these adrenal steroids mediate a plethora of physiological responses in both the periphery and the central nervous system. The collective actions of GCs in the brain are paradoxical, however, in that basal levels of GCs are essential for neuronal development, plasticity and survival, while stress levels of GCs produce neuronal loss. Aging represents another contradictory function of GCs in the brain, since lifelong exposure to GCs has been implicated as a causative factor in senescent neuronal loss. In addition, glucocorticoids have also been shown to intensify neuronal damage in the hippocampus during ischemia and excitotoxicity through mechanisms that modulate synaptic glutamate concentrations. Conversely, the absence of adrenal steroids has been shown to regulate both neurogenesis and neuronal loss in the dentate gyrus of the hippocampus. Evidence continues to accumulate which suggests that GC-induced neuronal death in all these physiological and pathophysiological settings occurs by apoptosis. Accordingly, this review will examine the pharmacological, cellular and molecular mechanisms through which glucocorticoids mediate or contribute to neuronal remodeling and, ultimately, neuronal death.
Reagan
L P
LP
Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, Rockefeller University, New York, NY 10021, USA.
McEwen
B S
BS
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D005938:Glucocorticoids / Q000502:physiology*; D006624:Hippocampus / Q000166:cytology*
D005938:Glucocorticoids