Effects of amyloid-β peptides on the serotoninergic 5-HT1A receptors in the rat hippocampus

Calcium Signaling and Amyloid Toxicity in Alzheimer Disease

“…Interactions of A␤ with various Ca 2ϩ -permeable channels have been established (31,32), including voltage-gated Ca 2ϩ channels (N, P, and Q), nicotinic acetylcholine channels (␣ 7 and ␣ 4 ␤ 2 ), glutamate receptors (AMPA and NMDA), dopamine receptors, serotonin receptors (5-hydroxytryptamine type 3), and intracellular inositol trisphosphate receptors (IP 3 Rs). Several lines of evidence point to complex dynamics between A␤ and both the cholinergic and glutamatergic neurotransmitter systems during the progression of AD (33,34).…”

“…In turn, this is linked to downstream pathogenic effects, such as dynamin 1 degradation, increased reactive oxygen species production, and aberrant calpain activation (43), all of which can impair synaptic integrity. Acute treatment studies applying A␤ and A␤ [25][26][27][28][29][30][31][32][33][34][35] peptides have demonstrated similar patterns of enhanced NMDA currents (44). In contrast, sustained exposure of neurons to A␤ oligomeric peptides reduces NMDA cell-surface expression, Ca 2ϩ influx, and glutamatergic currents (17,45,46).…”

Endoplasmic Reticulum Ca2+Handling in Excitable Cells in Health and Disease

“…As a third proposed mechanism, A␤ peptides have been shown to interact with several Ca 2ϩ -permeable channels and to increase Ca 2ϩ flux. These include several voltage-gated Ca 2ϩ channels, ␣-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid and NMDA glutamate receptors, and serotonergic (5-HT 3 ) and cholinergic (nicotinic ␣7 and ␣4␤2) receptors (Buckingham et al, 2009;Demuro et al, 2010;Verdurand et al, 2011).…”

Agonist and antagonist bind differently to 5-HT1A receptors during Alzheimer’s disease: A post-mortem study with PET radiopharmaceuticals

“…This observation was also replicated in our laboratory in a rodent model of AD where the infusion of the amyloid beta-40 peptide in the rat hippocampus induced a transient 5-HT 1A receptors overexpression specific to the dentate gyrus (Verdurand et al, 2011;2016).…”

“…On the contrary, an up-regulation of 5-HT 1A receptors has been reported at the Mild Cognitive Impairment (MCI) stage, prodromal of AD (Truchot et al, 2007;Truchot et al, 2008). The pathophysiological significance of this phenomenon remains to be elucidated, and could reflect compensatory mechanisms occurring at the earliest stages of this neurodegenerative disease (Truchot et al, 2007;Verdurand et al, 2011). …”