Reduced responses to glutamate receptor agonists follow loss of astrocytes and astroglial glutamate markers in the nucleus tractus solitarii

Saporin (SAP) or SAP conjugates injected into the nucleus tractus solitarii (NTS) of rats kill astrocytes. When injected in its unconjugated form, SAP produces no demonstrable loss of or damage to local neurons. However bilateral injections of SAP significantly attenuate responses to activation of baroreceptor reflexes that are mediated by transmission of signals through glutamate receptors in the NTS We tested the hypothesis that SAP would reduce cardiovascular responses to activation of NTS glutamate receptors despite its recognized ability to spare local neurons while killing local astrocytes. In animals treated with SAP and SAP conjugates or, as a control, with the toxin 6-hydroxydopamine (6-OHDA), we sought to determine if dose-related changes of arterial pressure (AP) or heart rate (HR) in response to injection into NTS of N-methyl-d-aspartate (NMDA) or α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) were attenuated. Also we quantified changes in immunoreactivity (IR) for EAAT2, EAAC1, and VGluT2 in NTS after SAP and SAP conjugates. Our earlier studies showed that IR for NMDA and AMPA receptors was not changed after injection of SAP We found that EAAT2 and EAAC1, both found in astrocytes, were reduced by SAP or its conjugates but not by 6-OHDA In contrast, VGluT2-IR was increased by SAP or conjugates but not by 6-OHDA AP and HR responses to NMDA and AMPA were attenuated after SAP and SAP conjugate injection but not after 6-OHDA Results of this study are consistent with others that have shown interactions between astroglia and neurons in synaptic transmission mediated by glutamate receptor activation in the NTS.