We previously reported that neuronal numbers within adult nodose ganglia (NG) were restored to normal levels 60 days following the capsaicin-induced destruction of nearly half of the neuronal population. However, the nature of this neuronal replacement is not known. Therefore, we aimed to characterize neural proliferation, neurochemical phenotypes, and functional recovery within adult rat NG neurons following capsaicin-induced damage. Sprague-Dawley rats received intraperitoneal injections of capsaicin or vehicle solution, followed by 5-bromo-2-deoxyuridine (BrdU) injections to reveal cellular proliferation. NG were collected at multiple times post-treatment (up to 300 days) and processed for immunofluorescence, RT-PCR, and dispersed cell cultures. Capsaicin-induced cellular proliferation, indicated by BrdU/Ki-67-labeled cells, suggests that lost neurons were replaced through cell division. NG cells expressed the stem cell marker, nestin, indicating that these ganglia have the capacity to generate new neurons. BrdU-incorporation within β-III tubulin-positive neuronal profiles following capsaicin suggests that proliferating cells matured to become neurons. NG neurons displayed decreased NMDAR expression up to 180-days post-capsaicin. However, both NMDAR expression within the NG and synaptophysin expression within the central target of NG neurons, the NTS, were restored to pre-injury levels by 300 days. NG cultures from capsaicin-treated rats contained bipolar neurons, normally found only during development. To test the functional recovery of NG neurons, we injected the satiety molecule, CCK. The effect of CCK on food intake was restored by 300-days post-capsaicin. This restoration may be due to the regeneration of damaged NG neurons or generation of functional neurons that replaced lost connections.

Capsaicin is a neurotoxin selective for C- and Adelta-type neurons. Systemic treatment with capsaicin is known to reduce this subpopulation in the dorsal root ganglia (DRG) of neonatal rats. To better understand the effects of capsaicin on adult afferent fibers, we examined DRG neurons retrogradely labeled by an i.p. injection of Fast Blue (FB) administered 3, 30, or 60 days after systemic capsaicin treatment (125 mg/kg i.p.). FB labeling in the 12th and 13th thoracic DRG was dramatically reduced 3 and 30 days post capsaicin (50% and 35% of control, respectively). However, the number of retrogradely labeled neurons rose to 65% of control by 60 days post capsaicin. In addition to FB labeling, we quantified the immunoreactivity of NR1, the obligatory N-methyl-D-aspartate receptor subunit, and Na(v)1.8, a DRG-specific sodium channel, in FB-labeled neurons as well as mRNA levels for both proteins in the 5th and 6th lumbar DRG. NR1 immunoreactivity and mRNA expression followed a pattern of early reduction and subsequent partial restoration similar to FB labeling. Na(v)1.8 immunoreactivity and mRNA expression dropped to approximately 50% of control at 3 days post capsaicin but completely recovered by 60 days. These data strongly support the conclusion that restoration of spinal afferent projections and signaling occurs in adult rats following capsaicin-induced damage.

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BackgroundLittle is known about the effects of social exclusion on youth with bipolar disorder (BD). Understanding these effects and the functional neural correlates of social exclusion in youth with BD may establish differences from healthy youth and help identify areas of intervention.MethodsWe investigated brain function in 19 youth with BD and 14 age and gender matched healthy control (HC) participants while performing Cyberball, an fMRI social exclusion task. Whole brain activation, region-of-interest, and functional connectivity were compared between groups and examined with behavioral measures.ResultsCompared with the HC group, youth with BD exhibited greater activation in the left fusiform gyrus (FFG) during social exclusion. Functional connectivity between the left FFG and the posterior cingulate/precuneus was significantly greater in the HC compared with the BD group. For the HC group only, age and subjective distress during Cyberball significantly predicted mean FFG activation. No significant differences in distress during social exclusion were found between groups.ConclusionAlthough preliminary due to small sample size, these data suggest that youth with BD process social exclusion in a manner that focuses on basic visual information while healthy youth make use of past experiences to interpret current social encounters. This difference may account for the social cognitive issues experienced by youth with BD, which can lead to more severe anxiety and mood symptoms.