Ventrolateral ventromedial hypothalamic nucleus GABA neuron adaptation to recurring Hypoglycemia correlates with up-regulated 5′-AMP-activated protein kinase activity
Gamma-aminobutyric acid (GABA) acts on ventromedial hypothalamic targets to suppress counter-regulatory hormone release, thereby lowering blood glucose. Maladaptive up-regulation of GABA signaling is implicated in impaired counter-regulatory outflow during recurring insulin-induced hypoglycemia (RII...
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2021
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oai:doaj.org-article:e5c981b3b0f343cda58add9656d98cc82021-12-02T01:20:20ZVentrolateral ventromedial hypothalamic nucleus GABA neuron adaptation to recurring Hypoglycemia correlates with up-regulated 5′-AMP-activated protein kinase activity10.3934/Neuroscience.20210272373-7972https://doaj.org/article/e5c981b3b0f343cda58add9656d98cc82021-09-01T00:00:00Zhttps://www.aimspress.com/article/doi/10.3934/Neuroscience.2021027?viewType=HTMLhttps://doaj.org/toc/2373-7972Gamma-aminobutyric acid (GABA) acts on ventromedial hypothalamic targets to suppress counter-regulatory hormone release, thereby lowering blood glucose. Maladaptive up-regulation of GABA signaling is implicated in impaired counter-regulatory outflow during recurring insulin-induced hypoglycemia (RIIH). Ventromedial hypothalamic nucleus (VMN) GABAergic neurons express the sensitive energy gauge 5′-AMP-activated protein kinase (AMPK). Current research used high-neuroanatomical resolution single-cell microdissection tools to address the premise that GABAergic cells in the VMNvl, the primary location of ‘glucose-excited’ metabolic-sensory neurons in the VMN, exhibit attenuated sensor activation during RIIH. Data show that during acute hypoglycemia, VMNvl glutamate decarboxylase65/67 (GAD)-immunoreactive neurons maintain energy stability, yet a regional subset of this population exhibited decreased GAD content. GABA neurons located along the rostrocaudal length of the VMNvl acclimated to RIIH through a shift to negative energy imbalance, e.g. increased phosphoAMPK expression, alongside amplification/gain of inhibition of GAD profiles. Acquisition of negative GAD sensitivity may involve altered cellular receptivity to noradrenergic input via α2-AR and/or β1-AR. Suppression of VMNvl GABA nerve cell signaling during RIIH may differentiate this neuroanatomical population from other, possibly non-metabolic-sensory GABA neurons in the MBH. Data here also provide novel evidence that VMNvl GABA neurons are direct targets of glucocorticoid control, and show that glucocorticoid receptors may inhibit RIIH-associated GAD expression in rostral VMNvl GABAergic cells through AMPK-independent mechanisms.Abdulrahman AlhamyaniPrabhat R Napit Haider Ali Mostafa MH IbrahimKaren P BriskiAIMS Pressarticlerecurrent insulin-induced hypoglycemiaventrolateral ventromedial hypothalamic nucleus-ventrolateral partglutamate decarboxylaseampkadrenergic receptorNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571ENAIMS Neuroscience, Vol 8, Iss 4, Pp 510-525 (2021) |
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recurrent insulin-induced hypoglycemia ventrolateral ventromedial hypothalamic nucleus-ventrolateral part glutamate decarboxylase ampk adrenergic receptor Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 |
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recurrent insulin-induced hypoglycemia ventrolateral ventromedial hypothalamic nucleus-ventrolateral part glutamate decarboxylase ampk adrenergic receptor Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Abdulrahman Alhamyani Prabhat R Napit Haider Ali Mostafa MH Ibrahim Karen P Briski Ventrolateral ventromedial hypothalamic nucleus GABA neuron adaptation to recurring Hypoglycemia correlates with up-regulated 5′-AMP-activated protein kinase activity |
description |
Gamma-aminobutyric acid (GABA) acts on ventromedial hypothalamic targets to suppress counter-regulatory hormone release, thereby lowering blood glucose. Maladaptive up-regulation of GABA signaling is implicated in impaired counter-regulatory outflow during recurring insulin-induced hypoglycemia (RIIH). Ventromedial hypothalamic nucleus (VMN) GABAergic neurons express the sensitive energy gauge 5′-AMP-activated protein kinase (AMPK). Current research used high-neuroanatomical resolution single-cell microdissection tools to address the premise that GABAergic cells in the VMNvl, the primary location of ‘glucose-excited’ metabolic-sensory neurons in the VMN, exhibit attenuated sensor activation during RIIH. Data show that during acute hypoglycemia, VMNvl glutamate decarboxylase65/67 (GAD)-immunoreactive neurons maintain energy stability, yet a regional subset of this population exhibited decreased GAD content. GABA neurons located along the rostrocaudal length of the VMNvl acclimated to RIIH through a shift to negative energy imbalance, e.g. increased phosphoAMPK expression, alongside amplification/gain of inhibition of GAD profiles. Acquisition of negative GAD sensitivity may involve altered cellular receptivity to noradrenergic input via α2-AR and/or β1-AR. Suppression of VMNvl GABA nerve cell signaling during RIIH may differentiate this neuroanatomical population from other, possibly non-metabolic-sensory GABA neurons in the MBH. Data here also provide novel evidence that VMNvl GABA neurons are direct targets of glucocorticoid control, and show that glucocorticoid receptors may inhibit RIIH-associated GAD expression in rostral VMNvl GABAergic cells through AMPK-independent mechanisms. |
format |
article |
author |
Abdulrahman Alhamyani Prabhat R Napit Haider Ali Mostafa MH Ibrahim Karen P Briski |
author_facet |
Abdulrahman Alhamyani Prabhat R Napit Haider Ali Mostafa MH Ibrahim Karen P Briski |
author_sort |
Abdulrahman Alhamyani |
title |
Ventrolateral ventromedial hypothalamic nucleus GABA neuron adaptation to recurring Hypoglycemia correlates with up-regulated 5′-AMP-activated protein kinase activity |
title_short |
Ventrolateral ventromedial hypothalamic nucleus GABA neuron adaptation to recurring Hypoglycemia correlates with up-regulated 5′-AMP-activated protein kinase activity |
title_full |
Ventrolateral ventromedial hypothalamic nucleus GABA neuron adaptation to recurring Hypoglycemia correlates with up-regulated 5′-AMP-activated protein kinase activity |
title_fullStr |
Ventrolateral ventromedial hypothalamic nucleus GABA neuron adaptation to recurring Hypoglycemia correlates with up-regulated 5′-AMP-activated protein kinase activity |
title_full_unstemmed |
Ventrolateral ventromedial hypothalamic nucleus GABA neuron adaptation to recurring Hypoglycemia correlates with up-regulated 5′-AMP-activated protein kinase activity |
title_sort |
ventrolateral ventromedial hypothalamic nucleus gaba neuron adaptation to recurring hypoglycemia correlates with up-regulated 5′-amp-activated protein kinase activity |
publisher |
AIMS Press |
publishDate |
2021 |
url |
https://doaj.org/article/e5c981b3b0f343cda58add9656d98cc8 |
work_keys_str_mv |
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