Details

Autor(en) / Beteiligte

• Zhang, Luoying
• Hirano, Arisa
• Hsu, Pei-Ken
• Jones, Christopher R.
• Sakai, Noriaki
• Okuro, Masashi
• McMahon, Thomas
• Yamazaki, Maya
• Xu, Ying
• Saigoh, Noriko
• Saigoh, Kazumasa
• Lin, Shu-Ting
• Kaasik, Krista
• Nishino, Seiji
• Ptáček, Louis J.
• Fu, Ying-Hui

Titel

A PERIOD3 variant causes a circadian phenotype and is associated with a seasonal mood trait

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 2016-03, Vol.113 (11), p.E1536-E1544

Ort / Verlag

United States: National Academy of Sciences

Erscheinungsjahr

2016

Quelle

MEDLINE

Beschreibungen/Notizen

• In humans, the connection between sleep and mood has long been recognized, although direct molecular evidence is lacking. We identified two rare variants in the circadian clock gene PERIOD3 (PER3-P415A/H417R) in humans with familial advanced sleep phase accompanied by higher Beck Depression Inventory and seasonality scores. hPER3-P415A/H417R transgenic mice showed an altered circadian period under constant light and exhibited phase shifts of the sleep-wake cycle in a short light period (photoperiod) paradigm. Molecular characterization revealed that the rare variants destabilized PER3 and failed to stabilize PERIOD1/2 proteins, which play critical roles in circadian timing. Although hPER3-P415A/H417R-Tg mice showed a mild depression-like phenotype, Per3 knockout mice demonstrated consistent depression-like behavior, particularly when studied under a short photoperiod, supporting a possible role for PER3 in mood regulation. These findings suggest that PER3 may be a nexus for sleep and mood regulation while fine-tuning these processes to adapt to seasonal changes.