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Effects of developmental N-Methyl D-aspartate (NMDA) receptor antagonism on adulthood hypothalamic gene expression in female C57Bl/6J mice.

ABSTRACT: AIM: to examine changes in hypothalamic gene expression following developmental N-Methyl D-aspartate (NMDA) receptor antagonism in adult female C57Bl/6J mice. AIM: to examine changes in hypothalamic gene expression following developmental N-Methyl D-aspartate (NMDA) receptor antagonism in adult female C57Bl/6J mice. This data will compliment on-going studies into the effect of developmental NMDA receptor antagonism on aspects of the Hypothalamic-Pituitary-Adrenal (HPA) axis.

ORGANISM(S): Mus musculus

PROVIDER: GSE108042 | GEO | 2019/12/13

REPOSITORIES: GEO

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Effects of developmental N-Methyl D-aspartate (NMDA) receptor antagonism on adulthood adrenal gene expression in female C57Bl/6J mice.

Project description:AIM: to examine changes in adrenal gene expression following developmental N-Methyl D-aspartate (NMDA) receptor antagonism in adult female C57Bl/6J mice. This data will compliment on-going studies into the effect of developmental NMDA receptor antagonism on aspects of the Hypothalamic-Pituitary-Adrenal (HPA) axis.

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Effects of developmental N-Methyl D-aspartate (NMDA) receptor antagonism on adulthood hypothalamic gene expression in female C57Bl/6J mice.

Project description:Effects of developmental N-Methyl D-aspartate (NMDA) receptor antagonism on adulthood hypothalamic gene expression in female C57Bl/6J mice.

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Effects of developmental N-Methyl D-aspartate (NMDA) receptor antagonism on adulthood adrenal gene expression in female C57Bl/6J mice.

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Gene expression changes in adrenal and hypothalamus following developmental N-Methyl D-aspartate (NMDA) receptor antagonism in adult female C57Bl/6J mice

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Expression data from adult mouse hypothalamus

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Project description:The N-methyl-D-aspartate (NMDA) receptor is a glutamate-activated cation channel critical to many processes in the brain. Genome-wide association studies (GWAS) suggest that glutamatergic neurotransmission and NMDA receptor-mediated synaptic plasticity is important for body weight homeostasis1. Here, we report the engineering and preclinical development of a first-in-class bimodal molecule that integrates NMDA receptor antagonism with glucagon-like peptide-1 (GLP-1) receptor agonism to effectively reverse obesity, hyperglycemia, and dyslipidemia in rodent models of metabolic disease. We demonstrate that GLP-1-directed delivery of the NMDA receptor antagonist MK-801 affects NMDA receptor-mediated synaptic plasticity in the hypothalamus. Importantly, peptide-targeting of MK-801 specifically to GLP-1 receptor-expressing brain regions circumvent adverse physiological and behavioral effects associated with MK-801 monotherapy. In sum, our approach demonstrates the feasibility of cell specific ionotropic receptor-modulation via peptide targeting and highlights the therapeutic potential of unimolecular mixed GLP-1 receptor agonism and NMDA receptor antagonism for obesity treatment.

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GLP-1 directed NMDA receptor antagonism for obesity treatment [I]

Project description:The N-methyl-d-aspartate (NMDA) receptor is a glutamate-activated cation channel critical to many processes in the brain. Genome-wide association studies (GWAS) suggest that glutamatergic neurotransmission and NMDA receptor-mediated synaptic plasticity is important for body weight homeostasis1. Here, we report the engineering and preclinical development of a first-in-class bimodal molecule that integrates NMDA receptor antagonism with glucagon-like peptide-1 (GLP-1) receptor agonism to effectively reverse obesity, hyperglycemia, and dyslipidemia in rodent models of metabolic disease. We demonstrate that GLP-1-directed delivery of the NMDA receptor antagonist MK-801 affects NMDA receptor-mediated synaptic plasticity in the hypothalamus. Importantly, peptide-targeting of MK-801 specifically to GLP-1 receptor-expressing brain regions circumvent adverse physiological and behavioral effects associated with MK-801 monotherapy. In sum, our approach demonstrates the feasibility of cell specific ionotropic receptor-modulation via peptide targeting and highlights the therapeutic potential of unimolecular mixed GLP-1 receptor agonism and NMDA receptor antagonism for obesity treatment.

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Expression data from adult mouse adrenal tissue

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