Management of sleep/wake cycles improves cognitive function in a transgenic mouse model of Huntington's disease.
Normally, mice sleep during the day and are active at night. In Huntington's disease mice (R6/2 line) this circadian pattern disintegrates progressively over the course of their illness. Cognitive decline and apathy in R6/2 mice can be improved with sleeping drugs, suggesting that sleep disruption contributes to their neurological decline. We wondered if wakefulness was equally important. Here, we used two drugs to manage sleep/wake cycles in R6/2 mice, Alprazolam (to put them to sleep) and Modafinil (to wake them up). We found that both drugs improved cognitive function and apathy, but had a stronger effect when used in combination. Remarkably, beneficial effects on cognitive performance were also seen in vehicle-treated cage-mates of Alprazolam/Modafinil-treated mice, suggesting that behavioral intervention to regularize sleep/wake activity might be therapeutically useful. We suggest that focused management of sleep and wakefulness will slow the progression of cognitive decline and apathy in neurological conditions where sleep is disordered.
Pallier
Patrick N
PN
Department of Pharmacology, University of Cambridge, Cambridge, UK.
Morton
A Jennifer
AJ
D000339:Affect / Q000187:drug effects; D000525:Alprazolam / Q000008:administration & dosage; D000818:Animals; D001559:Benzhydryl Compounds / Q000008:administration & dosage; D001835:Body Weight / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000008:administration & dosage; D003071:Cognition / Q000187:drug effects*; D003072:Cognition Disorders / Q000150:complications / Q000188:drug therapy; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D005260:Female; D006816:Huntington Disease / Q000150:complications / Q000188:drug therapy*; D006993:Hypnotics and Sedatives / Q000008:administration & dosage; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D000077408:Modafinil; D012193:Reversal Learning / Q000187:drug effects; D012890:Sleep / Q000187:drug effects*; D014851:Wakefulness / Q000187:drug effects*
D001559:Benzhydryl Compounds; D000697:Central Nervous System Stimulants; D006993:Hypnotics and Sedatives; D000077408:Modafinil; D000525:Alprazolam