| First Author | Li YY | Year | 2023 |
| Journal | Neurobiol Aging | Volume | 124 |
| Pages | 71-84 | PubMed ID | 36758468 |
| Mgi Jnum | J:351246 | Mgi Id | MGI:7441769 |
| Doi | 10.1016/j.neurobiolaging.2023.01.008 | Citation | Li YY, et al. (2023) Orexin-A aggravates cognitive deficits in 3xTg-AD mice by exacerbating synaptic plasticity impairment and affecting amyloid beta metabolism. Neurobiol Aging 124:71-84 |
| abstractText | 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 beta (Abeta) levels are unknown. In the present study, the effects of OXA on cognitive functions, synaptic plasticity, Abeta 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 Abeta 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 Abeta production and decreasing Abeta clearance through disruption of the circadian rhythm and sleep-wake cycle. |
