Ventrolateral ventromedial hypothalamic nucleus GABA neuron adaptation to recurring Hypoglycemia correlates with up-regulated 5′-AMP-activated protein kinase activity
| Autor: | Prabhat R. Napit, Haider Ali, Abdulrahman Alhamyani, Karen P. Briski, Mostafa M.H. Ibrahim |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
AMPK
education.field_of_study Cell signaling Adrenergic receptor Chemistry General Neuroscience Glutamate decarboxylase Population Glutamate receptor Neurosciences. Biological psychiatry. Neuropsychiatry recurrent insulin-induced hypoglycemia medicine.anatomical_structure Glucocorticoid receptor nervous system ventrolateral ventromedial hypothalamic nucleus-ventrolateral part medicine GABAergic glutamate decarboxylase Neuron education Neuroscience RC321-571 Research Article adrenergic receptor |
| Zdroj: | AIMS Neuroscience AIMS Neuroscience, Vol 8, Iss 4, Pp 510-525 (2021) |
| ISSN: | 2373-7972 2373-8006 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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