AMPK-dependent brain-wide norepinephrine release promotes recovery from metabolic coma in mice
Coma is a pathological brain state characterized by loss of consciousness. How the brain recovers from coma remains largely unknown. Using mouse models of metabolic coma, we identified an endogenous neuromodulatory pathway that actively promotes coma recovery. In mice subjected to hypoglycemic coma, hypoglycemia triggered AMPK-dependent excitation of nucleus tractus solitarius (NTS) neurons,…
Coma is a brain state marked by a loss of consciousness. The mechanisms behind brain recovery from coma remain largely unclear. Researchers have identified a neuromodulatory pathway in mice models of metabolic coma that actively facilitates recovery. Hypoglycemic coma in mice led to AMPK-triggered activation of nucleus tractus solitarius (NTS) neurons, which in turn activated locus coeruleus (LC) norepinephrine neurons via a glutamatergic NTS-LC circuit.
The activated LC neurons released norepinephrine across cortical and subcortical regions, promoting post-coma arousal. The released norepinephrine was significantly higher, approximately 10 times more than normal norepinephrine release during sleep-wake cycles. This process also occurred during hypercapnic coma. Vagus nerve stimulation hastened coma recovery by activating this endogenous anti-coma mechanism.
The study reveals an AMPK-dependent brainstem circuit that actively restores arousal from metabolic coma, unveiling a neural defense strategy against severe metabolic stress.
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