Optogenetic stimulation of vlPAGvglut2 neurons induced hypothermia and cardiovascular depression in healthy mice, whereas their genetic ablation attenuated these responses during systemic inflammation.
Does modulation of vlPAGvglut2 neurons affect hypothermia and cardiovascular depression in mouse models of systemic inflammation?
Identification of a vlPAG excitatory circuit driving hypometabolic responses to systemic inflammation provides potential therapeutic targets for mitigating severe sepsis-induced hypothermia and cardiovascular dysfunction.
Summary Hypometabolism, characterized by hypothermia and cardiovascular depression, is associated with higher mortality in patients with septic shock. However, the neural substrates underlying the hypometabolic state during systemic inflammation remain poorly understood. Here, using activity-dependent genetic labeling of neurons activated by lipopolysaccharide (LPS) administration and cecal ligation and puncture (CLP) in mice, we identified a discrete population of glutamatergic neurons in the ventrolateral periaqueductal gray (vlPAG) that drives hypothermia and cardiovascular depression. Optogenetic stimulation of vlPAGvglut2 neurons induced hypothermia and cardiovascular depression in healthy mice, whereas their genetic ablation attenuated the reductions in core temperature and cardiovascular function observed during systemic inflammation. Furthermore, we demonstrated that projections from vlPAGvglut2 neurons to the nucleus tractus solitarius mediate these hypometabolic pathophysiological effects. Taken together, our findings reveal a vlPAG excitatory circuit that regulates hypometabolic responses to systemic inflammation, providing potential therapeutic targets for mitigating severe sepsis-induced hypothermia and cardiovascular dysfunction.
Xie et al. (Wed,) conducted a other in Systemic inflammation. Optogenetic stimulation or genetic ablation of vlPAGvglut2 neurons was evaluated on Hypothermia and cardiovascular depression. Optogenetic stimulation of vlPAGvglut2 neurons induced hypothermia and cardiovascular depression in healthy mice, whereas their genetic ablation attenuated these responses during systemic inflammation.