Sleep-active hypothalamic MCH-system modulates hippocampal synaptic plasticity and is vulnerable in early Alzheimer’s Disease
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ABSTRACT:
PROVIDER: PRJNA934309 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR23440367.fastq.gz | Fastqsanger.gz | |||
| SRR23440368.fastq.gz | Fastqsanger.gz | |||
| SRR23440369.fastq.gz | Fastqsanger.gz | |||
| SRR23440370.fastq.gz | Fastqsanger.gz | |||
| SRR23440371.fastq.gz | Fastqsanger.gz |
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Project description:Orexin/hypocretin receptor type 2 (Ox2R), which is widely expressed in the brain, receives orexin signals and modulates sleep and metabolism. Ox2R selective agonists are currently under clinical trials for narcolepsy treatment. Nevertheless, it remains unclear whether Ox2R exerts an inhibitory effect via Gi proteins in addition to an excitatory effect via Gq proteins. Here, we focused on Ox2R expression and function in MCH neurons, which have opposite roles to orexin neurons in sleep and metabolism regulation. Ox2R-expressing MCH neurons showed heterogeneity of RNA expression, and orexin B application in brain slices induced both excitatory and inhibitory responses in distinct MCH neuron populations. Ox2R inactivation in MCH neurons reduced transitions from NREM to REM sleep and impaired insulin sensitivity with hyperphagia. In conclusion, Ox2R mediates excitatory and inhibitory responses in MCH neuron subpopulations in vivo, which might regulate sleep and metabolism.
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