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Essential and sex-specific effects of mGluR5 in ventromedial hypothalamus regulating estrogen signaling and glucose balance
Key and sex-specific roles of mGluR5 in the brain's energy control area affecting estrogen signals and blood sugar balance
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Abstract
Expression of metabotropic glutamate receptor subtype 5 (mGluR5) in the ventromedial hypothalamus (VMH) is reduced in severely obese brain-derived neurotrophic factor (BDNF) mutant mice.
- mGluR5 depletion in VMH SF1 neurons does not impact energy balance regulation.
- Impairments in insulin sensitivity, glycemic control, lipid metabolism, and sympathetic output are observed in females but not in males with mGluR5 depletion.
- Sex-specific deficits are associated with reduced intrinsic excitability and firing rate of SF1 neurons.
- Altered synapse assembly and increased expression of the GABAergic synthetic enzyme GAD67 affect synaptic excitatory and inhibitory tone in mutant SF1 neurons.
- Disrupted interactions between mGluR5 and estrogen receptors change the effects of estrogen on SF1 neuronal activity and glucose control from protective to harmful.
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