Involvement of orexin nerves in early stage of Alzheimer's disease model mice and preventive effect of orexin receptor antagonists - PubMed

a day ago

Orexin (OX) levels are elevated in the cerebrospinal fluid of patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD).
The study investigated the efficacy of dual OX receptor antagonists (suvorexant and lemborexant) in an early-stage AD mouse model (App-KI).
OX receptor gene expression was highest in the lateral hypothalamus of wild-type mice and was also observed in other brain regions.
OX1R gene expression was significantly increased in these brain regions in App-KI mice.
Brain concentrations of suvorexant peaked 20 to 40 min after administration, and those of lemborexant peaked 15 min after administration.
Motor activity decreased following the administration of either suvorexant or lemborexant, but no difference was observed compared to the control group 24 h later.
Suvorexant and lemborexant mitigated cognitive impairment in App-KI mice, as revealed by the Y-maze test.
Both drugs suppressed the accumulation of Aβ in the CA1 region of the hippocampus in App-KI mice, associated with increased Aβ uptake by activated microglia.
The results suggest that suvorexant and lemborexant effectively suppress the early stages of AD.

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