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Age- and Hypertension-Related Neurochemical Remodeling in the Jugular–Nodose Ganglion Complex of Rats: Asymmetry and Plasticity of CGRP, nNOS, and TTN3 Expression
* 1 , 2 , 2
1  Faculty of Medicine, Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania
2  Institute of Anatomy, Lithuanian University of Health Sciences, Kaunas, Lithuania
Academic Editor: Alberto Ouro

Abstract:

The jugular–nodose ganglion (JNG) complex of the vagus nerve is a key autonomic relay. However, how aging and hypertension affect its neuropeptide expression remains unclear. This study examined age-, strain-, and side-dependent expression of CGRP, nNOS, and TTN3 in spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats.

Methods:
Male SHR and WKY rats were grouped as young (4–9 weeks), middle-aged (39–42 weeks), or old (60–63 weeks). JNG tissues were processed for immunohistochemistry with antibodies against CGRP, nNOS, and TTN3. Neuronal expression was quantified bilaterally and compared using unpaired and paired t-tests.

Results:
In young rats, CGRP-positive neurons accounted for 11.05% in SHR and 0.98% in WKY (p = 0.0007); in middle-aged rats – 6.79% vs. 0.32% (p < 0.0001); no significant difference in old rats (28.36% vs. 34.45%, p = 0.11). nNOS expression was lower in young SHR (3.35%) than WKY (37.07%, p = 0.01) but similar in middle-aged (31.64% vs. 29.78%) and old rats (40.27% vs. 38.53%). TTN3-positive neurons were more frequent in SHR across all ages: young (70.13% vs. 47.23%, p < 0.0001), middle-aged (42.56% vs. 78.30%, p = 0.0025), and old (70.11% vs. 44.22%, p = 0.0086). Neuron size in SHR increased with age (Me = 23.23→24.97 µm²), whereas WKY showed no significant change. Neuron density was higher in young SHR (762/mm²) vs. WKY (608/mm²) and declined with age. Ganglion area correlated positively with neuron number in young and middle-aged but not old animals.

Discussion:
Hypertension induces dynamic, age-dependent neurochemical and morphological remodeling of the JNG. Elevated CGRP, reduced nNOS, and persistent TTN3 upregulation suggest adaptive–maladaptive interplay in baroreceptor pathways. Although these results were obtained in rats, the JNG shares key molecular features with the human vagus nerve. Direct evidence of age- or hypertension-related morphological changes in human vagal ganglia is still lacking, but many mammalian species exhibit comparable autonomic aging, supporting the translational relevance of these findings.

Keywords: Hypertension; vagus nerve; aging; autonomic nervous system; neuropeptides

 
 
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