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P1‐447: Time‐course effects of amyloid toxicity induced by a single icv injection of Aβ(25–35) on the glucocorticoids system in rats
Author(s) -
Brureau Anthony,
Zussy Charleine,
Delair Brice,
Maurice Tangui,
Givalois Laurent
Publication year - 2008
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2008.05.1029
Subject(s) - medicine , endocrinology , hippocampal formation , corticosterone , neurodegeneration , hippocampus , senile plaques , receptor , dexamethasone , glucocorticoid receptor , chemistry , alzheimer's disease , hormone , disease
Background: Alzheimer’s disease (AD) is a neurodegenerative pathology characterized by the presence of senile plaques and neurofibrillary tangles, accompanied by synaptic and neuronal loss. The major component of senile plaques is a -amyloid protein (A ). Intracerebral injection of A to rodents induces learning and memory impairments as well as neurodegeneration in brain area related to cognitive functions. In AD patients, it was also observed some endocrine modifications and more particularly changes in the hypothalamo-pituitary-adrenocortical (HPA) axis activity, which are characterized by an hyper-secretion of glucocorticoids. Methods: In this study, we assessed the time-course effects (during 6 weeks) of a single intracerebroventricular (icv) injection of aggregated A fragment (25-35) at a dose of 10 g/rat on the glucocorticoids system. The hippocampal, amygdala, frontal cortex and hypothalamic mRNA and protein levels (RT-PCR and western blot) of glucocorticoids receptors (MR and GR) were evaluated before and 1, 2, 3 and 6 weeks after the single icv injection of A (25-35). The effects of A icv injection on the subcellular localization of glucocorticoids receptors were also evaluated by immunohistochemistry. Plasmatic concentrations of ACTH and corticosterone (CORT) were determined (RIA) before and after A (25-35) injection. The eventual modification of glucocorticoids feedback following the single icv injection of A (25-35) was estimated with the dexamethasone (DEX) suppression test. The icv injection of scrambled A (25-35) peptide was used as sham control. Results: The results show that aggregated A (25-35) affects differentially the expression of GR and MR over the time and the cerebral region considered. It seems that amyloid peptide induces a progressive localization of GR in the nucleolus over the time, which is more pronounced in the frontal cortex, the amygdala and the hippocampus than in the hypothalamus. Plasma concentrations of ACTH are significantly increased only 3 and 6 weeks after the single injection of A (25-35), while the plasma concentrations of CORT are significantly increased after 1, 2, 3 and 6 weeks. Conclusions: In conclusion, this study shows that A (25-35) seems to induce a glucocorticoids resistance that could initiate and/or contribute to cognitive and physiological deficits at an early stage of Alzheimer’s disease.