Intranasal delivery of kisspeptin-54 improved mood-related disorders in hemiparkinsonian rats

Abstract

This study was designed to investigate whether chronic intranasal administration of kisspeptin-54 ameliorates anxiogenic- and depressive-like behaviors in the 6-hydroxydopamine (6-OHDA) unilaterally lesioned rats. We also tested the hypothesis that intranasal delivery of kisspeptin-54 would prevent against dopaminergic neuron loss in hemiparkinsonian rats. Male adult Sprague Dawley rats (age, 12 weeks; weight, 280-300 g) received a unilateral injection of 6-OHDA or vehicle into the medial forebrain bundle. Vehicle or kisspeptin-54 treatments (0.1, 0.3, 1, and 3 nmol applied topically on the rhinarium) were performed for 7 consecutive days following 6-OHDA surgery. Seven days after the lesion surgery, the sucrose preference test (SPT) and elevated plus maze test (EPMT) were used to measure depression- and anxiety-like behaviors, respectively. Tyrosine hydroxylase immunoreactivity in substantia nigra and striatum was analyzed by immunohistochemistry. Outcomes were analyzed between the experimental groups using ANOVA followed by Tukey posthoc test. As compared with sham-operated control rats (entry: 12 ± 2.3, time: 61.9 ± 1.6 s, n=10), 6-OHDA-lesioned rats made fewer open arm entries (6.1 ± 1, p<0.05, n=10) and spent less time (27.1 ± 3.9 s, p<0.05, n=10) on the open arms of EPM, inducing an anxiety-like behavior. In contrast, 6-OHDA-induced changes were found to be significantly (entry: 7.2-10.1 ± 2-1.7, time: 26.6-58.8 ± 2.5-3.1 s, p<0.05, n=10) improved in rats that received the chronic treatment of central kisspeptin-54 (dose-dependently). In the SPT, 6-OHDA-lesioned rats showed a lower (56.3 ± 3.5%, p<0.05, n=10) sucrose preference (considered an index of depression) in comparison to controls (80.7 ± 1.8%, n=10), and this decrease was dose-dependently restored to control levels by chronic kisspeptin-54 treatment (70.1-80.2 ± 2.8-2.7%, p<0.05, n=10). We also found that central kisspeptin-54 treatment significantly (p<0.05, n=5) attenuated the 6-OHDA-induced loss of dopaminergic nigrostriatal neurons. These data suggest that intranasal treatment of kisspeptin-54 improves 6-OHDA-induced anxiogenic- and depressive-like behaviors. Further, central kisspeptin-54 appears to be a promising therapeutic candidate for the treatment of mood-related disorders in Parkinson’s disease patients. The present study was supported by The Research Foundation of Akdeniz University (project number: TSA-2022-5909) This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.