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P1–076: Effect of chronic lithium treatment on a transgenic mouse model of Alzheimer's disease
Author(s) -
Martı́n-Aparicio Ester,
Fuertes-Huerta Ana,
Pérez-Puerto Marı́a José,
Navarro Marı́a Luisa,
del Monte-Millán Maria,
Martı́nez Ana,
Medina Miguel
Publication year - 2006
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.2006.05.451
Subject(s) - gsk 3 , glycogen synthase , lithium (medication) , gsk3b , hyperphosphorylation , genetically modified mouse , transgene , neurotoxicity , endocrinology , medicine , morris water navigation task , phosphorylation , neuroprotection , chemistry , hippocampus , biology , microbiology and biotechnology , glycogen , biochemistry , toxicity , gene
neuroinflammation and the number and morphology of the forebrain cholinergic neurons, by means of histochemistry and single and double labelling immunohistochemistry, the extracellular cortical acetylcholine levels in vivo, by means of the microdialysis technique, and the ability to acquire an inhibitory avoidance response in the “step-down” test. Neuronal shrinkage, particularly in correspondence to A (1-42)-immunopositive deposits, and white matter demyelination were widespread in the transgenic mouse brain. In the brain areas where a strong A (1-42) deposition and numerous plaques were detected, reactive microglia and hyperthrophic astrocytes were found infiltrating and surrounding A (1-42)-immunopositive deposits, respectively. A significant reduction in the number of choline acetyltransferase (ChAT)-positive neurons in the nucleus basalis magnocellularis and a decrease of both basal and K -stimulated extracellular acetylcholine (ACh) levels in the frontal cortex of TgCRND8 mice, respect to non transgenic controls, were found. m2 muscarinic receptor-immunoreactivity was significantly reduced in the primary motor cortex of TgCRND8 mice and no increase in the extracellular ACh levels was brought about by the administration of 0.5 mg/kg i.p. of the muscarinic antagonist scopolamine. A significant cognitive impairment was demonstrated in the step-down test. These findings demonstrate that neuronal damage and cholinergic dysfunction in vivo may underlie the impairment in learning and memory functions in this mouse model of Alzheimer’s disease.