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Dopamine-inhibited POMCDrd2+ neurons in the ARC acutely regulate feeding and body temperature.

ABSTRACT: Dopamine acts on neurons in the arcuate nucleus (ARC) of the hypothalamus, which controls homeostatic feeding responses. Here we demonstrate a differential enrichment of dopamine receptor 1 (Drd1) expression in food intake-promoting agouti related peptide (AgRP)/neuropeptide Y (NPY) neurons and a large proportion of Drd2-expressing anorexigenic proopiomelanocortin (POMC) neurons. Owing to the nature of these receptors, this translates into a predominant activation of AgRP/NPY neurons upon dopamine stimulation and a larger proportion of dopamine-inhibited POMC neurons. Employing intersectional targeting of Drd2-expressing POMC neurons, we reveal that dopamine-mediated POMC neuron inhibition is Drd2 dependent and that POMCDrd2+ neurons exhibit differential expression of neuropeptide signaling mediators compared with the global POMC neuron population, which manifests in enhanced somatostatin responsiveness of POMCDrd2+ neurons. Selective chemogenetic activation of POMCDrd2+ neurons uncovered their ability to acutely suppress feeding and to preserve body temperature in fasted mice. Collectively, the present study provides the molecular and functional characterization of POMCDrd2+ neurons and aids our understanding of dopamine-dependent control of homeostatic energy-regulatory neurocircuits.

SUBMITTER: Gaziano I

PROVIDER: S-EPMC9675440 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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Dopamine-inhibited POMCDrd2+ neurons in the ARC acutely regulate feeding and body temperature.

Gaziano Isabella I Corneliussen Svenja S Biglari Nasim N Neuhaus René R Shen Linyan L Sotelo-Hitschfeld Tamara T Klemm Paul P Steuernagel Lukas L De Solis Alain J AJ Chen Weiyi W Wunderlich F Thomas FT Kloppenburg Peter P Brüning Jens C JC

JCI insight 20221108 21

Dopamine acts on neurons in the arcuate nucleus (ARC) of the hypothalamus, which controls homeostatic feeding responses. Here we demonstrate a differential enrichment of dopamine receptor 1 (Drd1) expression in food intake-promoting agouti related peptide (AgRP)/neuropeptide Y (NPY) neurons and a large proportion of Drd2-expressing anorexigenic proopiomelanocortin (POMC) neurons. Owing to the nature of these receptors, this translates into a predominant activation of AgRP/NPY neurons upon dopami ...[more]

PMID: 36345942

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Project description:OBJECTIVES:Impaired cerebral autoregulation following neurologic injury is a predictor of poor clinical outcome. We aimed to assess the relationship between body temperature and cerebral autoregulation in comatose patients. DESIGN:Retrospective analysis of prospectively collected data. SETTING:Neurocritical care unit of the Johns Hopkins Hospital. PATIENTS:Eighty-five acutely comatose patients (Glasgow Coma Scale score of ≤ 8) admitted between 2013 and 2017. INTERVENTIONS:None. MEASUREMENT AND MAIN RESULTS:Cerebral autoregulation was monitored using multimodal monitoring with near-infrared spectroscopy-derived cerebral oximetry index. Cerebral oximetry index was calculated as a Pearson correlation coefficient between low-frequency changes in regional cerebral oxygenation saturation and mean arterial pressure. Patients were initially analyzed together, then stratified by temperature pattern over the monitoring period: no change (< 1°C difference between highest and lowest temperatures; n = 11), increasing (≥ 1°C; n = 9), decreasing (≥ 1°C; n = 9), and fluctuating (≥ 1°C difference but no sustained direction of change; n = 56). Mixed random effects models with random intercept and multivariable logistic regression analysis were used to assess the association between hourly temperature and cerebral oximetry index, as well as between temperature and clinical outcomes. Cerebral oximetry index showed a positive linear relationship with temperature (β = 0.04 ± 0.10; p = 0.29). In patients where a continual increase or decrease in temperature was seen during the monitoring period, every 1°C change in temperature resulted in a cerebral oximetry index change in the same direction by 0.04 ± 0.01 (p < 0.001) and 0.02 ± 0.01 (p = 0.12), respectively, after adjusting for PaCO2, hemoglobin, mean arterial pressure, vasopressor and sedation use, and temperature probe location. There was no significant difference in mortality or poor outcome (modified Rankin Scale score of 4-6) between temperature pattern groups at discharge, 3, or 6 months. CONCLUSIONS:In acute coma patients, increasing body temperature is associated with worsening cerebral autoregulation as measured by cerebral oximetry index. More studies are needed to clarify the impact of increasing temperature on cerebral autoregulation in patients with acute brain injury.

Dataset Information

Dopamine-inhibited POMCDrd2+ neurons in the ARC acutely regulate feeding and body temperature.

Publications

Dopamine-inhibited POMCDrd2+ neurons in the ARC acutely regulate feeding and body temperature.

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