Effects of altered corticosteroid milieu on rat hippocampal neurochemistry and structure--an in vivo magnetic resonance spectroscopy and imaging study.
Altered corticosteroid milieu induces changes in hippocampal volume, neuronal structure, neurochemistry and cognitive function in humans and rodents. This in vivo magnetic resonance spectroscopy (1H MRS) and imaging (MRI) study investigated whether long-term alterations of the corticosteroid milieu cause: (i) metabolic and/or (ii) structural changes of the rat hippocampus. Therefore, hypocortisolism was induced by adrenalectomy (ADX), normocortisolism by ADX with low-dose corticosterone replacement, and hypercortisolism by ADX and high-dose dexamethasone treatment (for 11 weeks, respectively). All groups including a control group (n=23) were studied by in vivo 1H MRS and MR volumetry. Effects of treatment on normalized hippocampal metabolites and volumes were tested for significance using one-factorial multivariate analysis of variance (MANOVA). Hypercortisolemic rats revealed significantly elevated glutamate. Hypocortisolemic rats showed significantly decreased myo-inositol ratio levels, and were associated with significantly reduced normalized hippocampal volumes. Our findings suggest chronic hypercortisolism to be associated with glutamate-mediated excitotoxicity in the absence of volumetric abnormalities. In contrast, hypocortisolism appears to be associated with neurodegenerative processes, altered astrocytic metabolism but preserved neuronal density.
Schubert
Mirjam I
MI
NMR Research Group, Max Planck Institute of Psychiatry, Munich, Germany. mirjam.schubert@nottingham.ac.uk
Kalisch
Raffael
R
Sotiropoulos
Ioannis
I
Catania
Caterina
C
Sousa
Nuno
N
Almeida
Osborne F X
OF
Auer
Dorothee P
DP
D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D001284:Atrophy; D002794:Choline / Q000378:metabolism; D003401:Creatine / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology*; D005938:Glucocorticoids / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D006854:Hydrocortisone / Q000502:physiology*; D007091:Image Processing, Computer-Assisted; D007294:Inositol / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D015999:Multivariate Analysis; D051381:Rats; D017208:Rats, Wistar
D005938:Glucocorticoids; D001224:Aspartic Acid; D018698:Glutamic Acid; D007294:Inositol; D003907:Dexamethasone; C000179:N-acetylaspartate; D003401:Creatine; D002794:Choline; D006854:Hydrocortisone