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Differential effects of short‐ and long‐term hyperhomocysteinaemia on cholinergic neurons, spatial memory and microbleedings in vivo in rats
Author(s) -
Pirchl Michael,
Ullrich Celine,
Humpel Christian
Publication year - 2010
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2010.07434.x
Subject(s) - choline acetyltransferase , medicine , endocrinology , cholinergic , cholinergic neuron , nerve growth factor , cortex (anatomy) , cerebral cortex , in vivo , biology , neuroscience , receptor , microbiology and biotechnology
Hyperhomocysteinaemia (HHcy) has been identified as a cardiovascular risk factor for neurodegenerative brain diseases. The aim of the present study was to investigate the effects of short (5 months) or long (15 months) HHcy in Sprague–Dawley rats in vivo . Short‐ and long‐term HHcy differentially affected spatial memory as tested in a partially baited eight‐arm radial maze. HHcy significantly reduced the number of choline acetyltransferase (ChAT)‐positive neurons in the basal nucleus of Meynert and ChAT‐positive axons in the cortex only after short‐term but not long‐term treatment, while acetylcholine levels in the cortex were decreased at both time points. Nerve growth factor (NGF) was significantly enhanced in the cortex only after 15 months of HHcy. HHcy did not affect cortical levels of amyloid precursor protein, beta‐amyloid(1‐42), tau and phospho‐tau181 and several inflammatory markers, as well as vascular RECA‐1 and laminin density. However, HHcy induced cortical microbleedings, as illustrated by intensive anti‐rat IgG‐positive spots in the cortex. In order to study the regulation of the key enzyme ChAT, organotypic rat brain slices were incubated with homocysteine, which induced a decline of ChAT that was counteracted by NGF treatment. In conclusion, our data demonstrate that chronic short‐ and long‐term HHcy differentially caused memory impairment, cholinergic dysfunction, NGF expression and vascular microbleedings.