title: Differential effects of amyloid-beta 1-40 and 1-42 fibrils on 5-HT1A serotonin receptors in rat brain.
abstract: Evidence accumulates suggesting a complex interplay between neurodegenerative processes and serotonergic neurotransmission. We have previously reported an overexpression of serotonin 5-HT1A receptors (5-HT(1A)R) after intrahippocampal injections of amyloid-beta 1-40 (Aβ40) fibrils in rats. This serotonergic reactivity paralleled results from clinical positron emission tomography studies with [(18)F]MPPF revealing an overexpression of 5-HT(1A)R in the hippocampus of patients with mild cognitive impairment. Because Aβ40 and Aβ42 isoforms are found in amyloid plaques, we tested in this study the hypothesis of a peptide- and region-specific 5-HT(1A)R reactivity by injecting them, separately, into the hippocampus or striatum of rats. [(18)F]MPPF in vitro autoradiography revealed that Aβ40 fibrils, but not Aβ42, were triggering an overexpression of 5-HT(1A)R in the hippocampus and striatum of rat brains after 7 days. Immunohistochemical approaches targeting neuronal precursor cells, mature neurons, and astrocytes showed that Aβ42 fibrils caused more pathophysiological damages than Aβ40 fibrils. The mechanisms of Aβ40 fibrils-induced 5-HT(1A)R expression remains unknown, but hypotheses including neurogenesis, glial expression, and axonal sprouting are discussed.
authors.affiliation: Université de Lyon; Lyon Neuroscience Research Center, CNRS UMR5292; INSERM U1028, Université Claude Bernard Lyon 1, Lyon, France. Electronic address: verdurand@cermep.fr.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Verdurand
authors.affiliation: Université de Lyon; Lyon Neuroscience Research Center, CNRS UMR5292; INSERM U1028, Université Claude Bernard Lyon 1, Lyon, France.
authors.forename: Fabien
authors.initials: F
authors.lastname: Chauveau
authors.affiliation: Université de Lyon; Lyon Neuroscience Research Center, CNRS UMR5292; INSERM U1028, Université Claude Bernard Lyon 1, Lyon, France.
authors.forename: Alexia
authors.initials: A
authors.lastname: Daoust
authors.affiliation: Université de Lyon; Lyon Neuroscience Research Center, CNRS UMR5292; INSERM U1028, Université Claude Bernard Lyon 1, Lyon, France.
authors.forename: Anne-Laure
authors.initials: AL
authors.lastname: Morel
authors.affiliation: CERMEP-Imaging Platform, Lyon, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Bonnefoi
authors.affiliation: CERMEP-Imaging Platform, Lyon, France.
authors.forename: François
authors.initials: F
authors.lastname: Liger
authors.affiliation: Université de Lyon; Lyon Neuroscience Research Center, CNRS UMR5292; INSERM U1028, Université Claude Bernard Lyon 1, Lyon, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Bérod
authors.affiliation: Université de Lyon; Lyon Neuroscience Research Center, CNRS UMR5292; INSERM U1028, Université Claude Bernard Lyon 1, Lyon, France; CERMEP-Imaging Platform, Lyon, France; Hospices Civils de Lyon, Lyon, France. Electronic address: zimmer@univ-lyon1.fr.
authors.forename: Luc
authors.initials: L
authors.lastname: Zimmer
mesh_terms: D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000008:administration & dosage*; D000818:Animals; D060825:Cognitive Dysfunction / Q000378:metabolism; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000378:metabolism*; D004195:Disease Models, Animal; D006624:Hippocampus / Q000000981:diagnostic imaging / Q000378:metabolism*; D007150:Immunohistochemistry; D007267:Injections; D008297:Male; D010446:Peptide Fragments / Q000008:administration & dosage*; D058225:Plaque, Amyloid / Q000378:metabolism; D049268:Positron-Emission Tomography; D051381:Rats; D017207:Rats, Sprague-Dawley; D044263:Receptors, Serotonin, 5-HT1 / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D044263:Receptors, Serotonin, 5-HT1; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42)
keywords: 5-HT1A receptors; Alzheimer's disease; Amyloid-beta peptides; Positron emission tomography; Serotonin