Rett syndrome (RTT) is a neurodevelopmental disorder caused by loss-of-function mutations in MECP2, which encodes the transcriptional regulator methyl-CpG-binding protein 2. Its core symptoms include problems with breathing control, which are most severe during wakefulness and are further exacerbated by behavioural arousal. Reduced levels of brain-derived neurotrophic factor (BDNF) are thought to be involved in the aetiology of respiratory dysfunction in RTT. Now, Katz et al. report that acute administration of LM22A-4, a partial BDNF mimetic, completely reverses spontaneous apnoeas (atypical breathing pauses) and respiratory dysregulation during behavioural arousal in Mecp2 mutant mice, an RTT model. Moreover, patch-clamp recordings in Mecp2-null brainstem slices indicate that LM22A-4 decreases synaptic hyperexcitability within specific cell groups in the brainstem’s respiratory network. These findings support the hypothesis that reduced BNDF signalling and respiratory dysfunction in RTT are linked and demonstrate the feasibility of improving neurological function in RTT by redressing imbalances in synaptic excitability. Page 1047
Development/DMM Virtual Meeting 2021
Welcoming new Editors to DMM
Editor-in-Chief Liz Patton wants DMM to strengthen its presence in the field of translational biology and to focus on the importance of disease mechanisms, just as much as models. To implement this vision, we are pleased to welcome new Editors Sally Dunwoodie (Victor Chang Cardiac Research Institute, Australia), Monkol Lek (Yale School of Medicine, USA) and Rickie Patani (Francis Crick Institute, London, UK) to the team.
Roles of the gut microbiome in colorectal cancer development
Going hand-in-hand, a new Perspective by Foegeding et al. explores the Western diet as a driver of dysbiosis in colorectal cancer while a new Review by Wang et al. focuses on microbiota-driven mechanisms that initiate sporadic colorectal cancer.
preLights – the latest disease modelling preprints
Head over to preLights for the digests of the latest preprints:
Erin McGregor highlights work by Nowicka et al. that suggests a potential connection between mitochondrial dysfunction and neurodegeneration.
Emma Wilson discusses work by Dagra et al., which highlights D2 receptors as a potential target that could be used to alleviate alpha-Synuclein pathology in Parkinson’s disease.
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