Orexin-A aggravates cognitive deficits in 3xTg-AD mice by exacerbating synaptic plasticity impairment and affecting amyloid ß metabolism.
Neurobiol Aging
; 124: 71-84, 2023 04.
Article
in En
| MEDLINE
| ID: mdl-36758468
ABSTRACT
Dementia is the main clinical feature of Alzheimer's disease (AD). Orexin has recently been linked to AD pathogenesis, and exogenous orexin-A (OXA) aggravates spatial memory impairment in APP/PS1 mice. However, the effects of OXA on other types of cognitive deficits, especially in 3xTg-AD mice exhibiting both plaque and tangle pathologies, have not been reported. Furthermore, the potential electrophysiological mechanism by which OXA affects cognitive deficits and the molecular mechanism by which OXA increases amyloid ß (Aß) levels are unknown. In the present study, the effects of OXA on cognitive functions, synaptic plasticity, Aß levels, tau hyperphosphorylation, BACE1 and NEP expression, and circadian locomotor rhythm were evaluated. The results showed that OXA aggravated memory impairments and circadian rhythm disturbance, exacerbated hippocampal LTP depression, and increased Aß and tau pathologies in 3xTg-AD mice by affecting BACE1 and NEP expression. These results indicated that OXA aggravates cognitive deficits and hippocampal synaptic plasticity impairment in 3xTg-AD mice by increasing Aß production and decreasing Aß clearance through disruption of the circadian rhythm and sleep-wake cycle.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Alzheimer Disease
Limits:
Animals
Language:
En
Journal:
Neurobiol Aging
Year:
2023
Type:
Article
Affiliation country:
China