| First Author | Wang X | Year | 2023 |
| Journal | Neurobiol Aging | Volume | 121 |
| Pages | 64-77 | PubMed ID | 36379094 |
| Mgi Jnum | J:344488 | Mgi Id | MGI:7410713 |
| Doi | 10.1016/j.neurobiolaging.2022.09.007 | Citation | Wang X, et al. (2023) Amyloid beta oligomers disrupt piriform cortical output via a serotonergic pathway. Neurobiol Aging 121:64-77 |
| abstractText | Although olfactory deficits have been found in patients with early-stage Alzheimer's disease (AD), the underlying mechanisms remain unclear. Here we investigated whether and how human amyloid beta (Abeta) oligomers affect neural activity in the piriform cortex (PC) slices of adult mice. We found that oligomeric Abeta1-42 decreased the excitability of pyramidal neurons in the anterior PC. The effect was not blocked by glutamate or GABA(A) receptor antagonists, suggesting that Abeta1-42-induced hypoactivity is independent of glutamatergic and GABAergic transmission. Interestingly, the hypoexcitability was occluded by serotonin (5-HT) and blocked by antagonists of 5-HT(2C) receptors, phospholipase C (PLC), and calcium-activated potassium (BK) channels. Furthermore, Abeta1-42 oligomers failed to increase K(+)-channel currents in the presence of a BK channel blocker. Finally, 5-HT(2C) receptor antagonist improved olfactory memory and odor discrimination in APP/PS1 mice. The above data indicate that Abeta disrupts olfactory information output from the PC via the 5-HT-5-HT(2C) receptor-PLC-BK channel pathway. This study reveals that serotonergic modulation is a potential novel therapeutic target for olfactory damage in AD. |
