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.

journal_name

Neurobiol Aging

journal_title

Neurobiology of aging

authors

Verdurand M,Chauveau F,Daoust A,Morel AL,Bonnefoi F,Liger F,Bérod A,Zimmer L

doi

10.1016/j.neurobiolaging.2015.12.008

subject

Has Abstract

pub_date

2016-04-01 00:00:00

pages

11-21

eissn

0197-4580

issn

1558-1497

pii

S0197-4580(15)00612-0

journal_volume

40

pub_type

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