bims-ciryme 2019-04-14 papers

Issue of 2019‒04‒14
two papers selected by
Gabriela Da Silva Xavier
University of Birmingham

JCI Insight. 2019 Apr 11. pii: 125133. [Epub ahead of print]5

Bmal1 deletion in mice facilitates adaptation to disrupted light/dark conditions.

Guangrui Yang, Lihong Chen, Jiayang Zhang, Baoyin Ren, Garret A FitzGerald.

Recently, by utilizing conventional and tamoxifen inducible Bmal1 (Brain and muscle Arnt-like protein 1) knockout mice, we found that delaying the loss of circadian rhythms to adulthood attenuates the impact on general integrity and survival at least under 12h light/12h dark conditions (LD). To understand further the contribution of Bmal1 in post-natal life under conditions of circadian disruption, we subjected inducible knockout mice (KO) and their littermate controls (Ctrl) to forced desynchrony protocols including cycles with non-24h periods, randomized light/dark cycles, and jet lag, and monitored their locomotor activity using radiotelemetry. Under these conditions, control mice cannot be entrained, as reflected by their maintenance of circadian behavior irrespective of schedules. By contrast, KO mice displayed higher activity levels in the dark phases of most cycles. Under a 3h light/3h dark regime, Ctrls displayed higher activity levels in the dark phases of all cycles although there were still obvious circadian rhythms, suggesting that an ultradian mechanism is also involved. Insulin sensitivity was markedly reduced by disrupted light schedules as expected in Ctrls, but not in the KOs. Thus, Bmal1 deletion in adult mice facilitates adaptation to new light/dark schedules and protects from insulin resistance induced by circadian disruption.

Keywords: Behavior; Mouse models; Neuroscience

DOI: https://doi.org/10.1172/jci.insight.125133

Elife. 2019 Apr 11. pii: e42819. [Epub ahead of print]8

Shank3 Modulates Sleep and Expression of Circadian Transcription Factors.

Ashley Ingiosi, Hannah Schoch, Taylor P Wintler, Kristan G Singletary, Dario Righelli, Leandro Roser, Elizabeth Medina, Davide Risso, Marcos G Frank, Lucia Peixoto.

Autism Spectrum Disorder (ASD) is the most prevalent neurodevelopmental disorder in the United States and often co-presents with sleep problems. Sleep problems in ASD predict the severity of ASD core diagnostic symptoms and have a considerable impact on the quality of life of caregivers. Little is known, however, about the underlying molecular mechanisms of sleep problems in ASD. We investigated the role of Shank3, a high confidence ASD gene candidate, in sleep architecture and regulation. We show that mice lacking exon 21 of Shank3 have problems falling asleep even when sleepy. Using RNA-seq we show that sleep deprivation increases the differences in prefrontal cortex gene expression between mutants and wild types, downregulating circadian transcription factors Per3, Bhlhe41, Hlf, Tef, and Nr1d1. Shank3 mutants also have trouble regulating wheel-running activity in constant darkness. Overall, our study shows that Shank3 is an important modulator of sleep and clock gene expression.

Keywords: mouse; neuroscience

DOI: https://doi.org/10.7554/eLife.42819