Pharmacological activation of the nuclear receptor REV-ERB reverses cognitive deficits and reduces amyloid-β burden in a mouse model of Alzheimer’s disease.

Autor: Roby, Deborah A., Ruiz, Fernanda, Kermath, Bailey A., Voorhees, Jaymie R., Niehoff, Michael, Zhang, Jinsong, Morley, John E., Musiek, Erik S., Farr, Susan A., Burris, Thomas P.
Předmět:
Zdroj: PLoS ONE; 4/12/2019, Vol. 14 Issue 4, p1-15, 15p
Abstrakt: Alzheimer’s disease currently lacks treatment options that effectively reverse the biological/anatomical pathology and cognitive deficits associated with the disease. Loss of function of the nuclear receptor REV-ERB is associated with reduced cognitive function in mouse models. The effect of enhanced REV-ERB activity on cognitive function has not been examined. In this study, we tested the hypothesis that enhanced REV-ERB function may enhance cognitive function in a model of Alzheimer’s disease. We utilized the REV-ERB agonist SR9009 to pharmacologically activate the activity of REV-ERB in the SAMP8 mouse model of Alzheimer’s disease. SR9009 reversed cognitive dysfunction of an aged SAMP8 mouse in several behavioral assays including novel object recognition, T-maze foot shock avoidance, and lever press operant conditioning task assessments. SR9009 treatment reduced amyloid-β 1–40 and 1–42 levels in the cortex, which is consistent with improved cognitive function. Furthermore, SR9009 treatment led to increased hippocampal PSD-95, cortical synaptophysin expression and the number of synapses suggesting improvement in synaptic function. We conclude that REV-ERB is a potential target for treatment of Alzheimer’s disease. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje