Neuroplasticity in the nucleus tractus solitarius precedes development of functional changes in autonomic regulation of arterial pressure in obese Zucker rats

Abstract

Obese Zucker rats (OZR) develop elevated sympathetic nerve activity (SNA) and arterial pressure (AP) between 7–14 wks of age vs. lean Zucker rats (LZR). Baroreflexes are normal in juvenile OZR (7 wk), but impaired in adult OZR (12–14 wk). In adult OZR baroreceptor afferent nerves respond normally to rises in MAP, but direct stimulation of afferents evokes blunted decreases in SNA and MAP, suggesting changes in the brain impair baroreflexes. We examined if nucleus tractus solitarius (NTS), the brain site receiving baroreceptor inputs, is affected in adult OZR. Stimulation of NTS by microinjections of glutamate evoked comparable decreases in SNA and MAP in juvenile OZR vs. LZR, but reduced responses in adult OZR vs. LZR. However, stimulation the caudal ventrolateral medulla, a target of the NTS, evoked comparable decreases in SNA and MAP in adult OZR and LZR. We examined the time course of changes in NTS by expression of ΔFosB protein as a marker of neuroplasiticity. At 5 wks OZR and LZR had comparable ΔFosB+ neurons (203±30 vs. 195±22). However, by 7 wks NTS of OZR had more ΔFosB+ neurons than LZR (514.5±70 vs. 207±24.5; P = 0.027), which persisted at 12 wks (177±15.38 in OZR and 88±15.76 in LZR; P = 0.02). These data suggest reduced excitability of NTS neurons contributes to blunted baroreflexes in adult OZR. Furthermore, changes in the NTS occur prior to the onset of altered baseline SNA and MAP or NTS function. Funding: NIHHL086759.