Differential effects of amyloid-beta 1-40 and 1-42 fibrils on 5-HT1A serotonin receptors in rat brain

摘要

Evidence accumulates suggesting a complex interplay between neurodegenerative processes and serotonergic neurotransmission. We have previously reported an overexpression of serotonin 5-HT1A receptors (5-HT1AR) after intrahippocampal injections of amyloid-beta 1-40 (A beta 40) fibrils in rats. This serotonergic reactivity paralleled results from clinical positron emission tomography studies with [F-18] MPPF revealing an overexpression of 5-HT1AR in the hippocampus of patients with mild cognitive impairment. Because A beta 40 and A beta 42 isoforms are found in amyloid plaques, we tested in this study the hypothesis of a peptide-and region-specific 5-HT1AR reactivity by injecting them, separately, into the hippocampus or striatum of rats. [F-18] MPPF in vitro autoradiography revealed that A beta 40 fibrils, but not A beta 42, were triggering an overexpression of 5-HT1AR in the hippocampus and striatum of rat brains after 7 days. Immunohistochemical approaches targeting neuronal precursor cells, mature neurons, and astrocytes showed that A beta 42 fibrils caused more pathophysiological damages than A beta 40 fibrils. The mechanisms of A beta 40 fibrilseinduced 5-HT1AR expression remains unknown, but hypotheses including neurogenesis, glial expression, and axonal sprouting are discussed. (C) 2016 Elsevier Inc. All rights reserved.