NEUROPLASTICITY IN THE NUCLEUS TRACTUS SOLITARIUS PRECEDES DEVELOPMENT OF FUNCTIONAL CHANGES IN AUTONOMIC REGULATION OF ARTERIAL PRESSURE IN OBESE ZUCKER RATS.

Purpose: In juvenile OZR (7 wks) splanchnic sympathetic nerve activity (SNA), mean arterial pressure (MAP), and arterial baroreflex-mediated control of SNA are comparable to LZR. In contrast, in adult OZR (12-14 wks), baseline SNA and MAP are elevated and baroreflexes are blunted compared to age-matched LZR. Baroreceptor afferent nerves of adult OZR respond normally to rises in MAP, but direct stimulation of the afferent fibers evokes blunted decreases in SNA and MAP, suggesting changes in the brain contribute to impaired baroreflexes. Activation of the nucleus of the solitary tract (NTS), the brain stem site that receives baroreceptor inputs, by microinjection of glutamate evokes comparable decreases in SNA and MAP in juvenile OZR and LZR but blunted responses in adult OZR. In contrast, activation of the brain stem target of the NTS, the caudal ventrolateral medulla, evokes comparable responses in adult OZR and LZR, suggesting the NTS is the major site that is impaired in adult OZR. The present study sought to determine the time course and the phenotype of NTS neurons that may be altered in OZR to contribute to impaired physiological responses. Methods: Zucker rats (5-6 wk, 7-8 wk and 11-12 wk, 6/group) were transcardially perfused with 4% paraformaldehyde. Brains were harvested and fixed for 48 hours. Then the brains were cut in the coronal plane (30 microns) using a Vibratome and stored in cryoprotectant for later histological processing. To identify neurons undergoing neuroplasticity in the intermediate NTS, we performed immunohistochemistry for ΔFosB revealed by 3, 3'-diaminobenzidine. Results: At 5 wks OZR and LZR had comparable numbers of ΔFosB+ neurons in the NTS (203±30; 195±22, P=0.85). In contrast, at 7 wks and 12 wks OZR had significantly more ΔFosB+ neurons versus age-matched LZR (7 wks: 514.5±70; 207±24.5, P <0.05). (12 wks: 177±15.38; 88±15.76, P <0.05). The ΔFosB positive neurons were not catecholaminergic (immunoreactive for tyrosine hydroxylase). Conclusions: These results suggest noncatecholaminergic NTS neurons undergo neuroplasticity in the OZR prior to the onset of hypertension or impaired baroreflexes, and these changes persist in adulthood.