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Astrocytic lesions that spare neurons in the nucleus tractus solitarii interfere with cardiorespiratory control

Richerson GB, Dragon DN, Jones S, Wu Y, Talman WT (2015) Astrocytic lesions that spare neurons in the nucleus tractus solitarii interfere with cardiorespiratory control. Neuroscience 2015 Abstracts 297.15/B100. Society for Neuroscience, Chicago IL.

Summary: Conjugates of saporin (SAP) have been widely used to target specific neurons while leaving other neurons undisturbed. We found that killing catecholamine neurons bilaterally in the nucleus tractus solitarii (NTS) by injection of the SAP conjugate containing an antibody to dopamine-_-hydroxylase (anti-DBH-SAP) spared non-catecholamine neurons but led to attenuation of baroreceptor reflexes, lability of arterial pressure, and, in some animals, sudden death. In contrast, selective targeting of catecholamine neurons with 6-hydroxydopamine produced no such cardiovascular events. We hypothesized that SAP conjugates may target non-neuronal cells in the NTS. Indeed, we found that local astrocytes were killed by the conjugates as well as by unconjugated SAP itself. SAP injections into the NTS led to death of astrocytes that expressed glial fibrillary acidic protein (GFAP) but did not affect neuronal structural markers and neuronal biosynthetic enzymes. Our recent studies further suggest that local neurons are physiologically intact. Nonetheless, SAP injections into the NTS significantly reduced cardiovascular responses elicited by glutamate agonists injected into the NTS, and bilateral injections of SAP into the NTS led to attenuation of cardiovascular reflexes whose pathways pass through the NTS, lability of arterial pressure, damage to cardiac myocytes and sudden death resulting from asystole. When asystole and death followed SAP treatment the fatal arrhythmia followed progressive bradycardia. In that treated animals demonstrate altered ventilatory function, we conjecture that it is altered ventilation that leads to cardiac compromise and death.

Related Products: Anti-DBH-SAP (Cat. #IT-03)

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