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Preparation of Acute Hippocampal Slices from Rats and Transgenic Mice for the Study of Synaptic Alterations during Aging and Amyloid Pathology
Published on: March 23, 2011
Aging attenuates glucocorticoid negative feedback in rat brain.
K Mizoguchi1, R Ikeda, H Shoji
1Section of Oriental Medicine, Department of Geriatric Medicine, National Institute for Longevity Sciences, National Center for Geriatrics and Gerontology, 36-3 Gengo, Morioka, Obu, Aichi 474-8522, Japan. k-mizo@nils.go.jp
Neuroscience
|January 15, 2009
Summary
Aging enhances the neuroendocrine system
Area of Science:
- Neuroendocrinology
- Aging research
- Neuroscience
Background:
- Aging can increase vulnerability of the neuroendocrine system, particularly the hypothalamic-pituitary-adrenal (HPA) axis.
- Dysregulation of the HPA axis, marked by dexamethasone (DEX)-mediated negative feedback resistance, is observed in aging individuals.
Purpose of the Study:
- To investigate the influence of aging on the HPA axis feedback system, focusing on brain involvement.
- To compare the effects of DEX on corticosterone levels in young and aged rats, examining both systemic and central administration.
Main Methods:
- Systemic DEX injection and intracranial DEX infusion into the prefrontal cortex (PFC), hippocampus, and hypothalamus.
- Immunohistochemical and Western immunoblot analyses to assess glucocorticoid receptor (GR) expression and translocation in the pituitary and brain regions.
Main Results:
- Systemic DEX injection showed an enhanced suppressive response in aged rats compared to young rats.
- Intracranial DEX infusion into brain regions abolished the suppressive response in aged rats.
- Aged rats exhibited decreased GR expression in the brain but increased GR expression in the pituitary, with reduced GR translocation in the brain and enhanced translocation in the pituitary.
Conclusions:
- Aging enhances systemic HPA axis feedback, primarily involving the pituitary gland.
- Aging attenuates central HPA axis feedback within the brain, potentially contributing to neuroendocrine vulnerability in aging.
