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Depression and anxiety are prevalent neuropsychiatric conditions among patients with Parkinson's disease (PD), which may manifest prior to motor symptoms. As levodopa, a prominent treatment for PD motor symptoms, provides few benefits for mood-related abnormalities, tackling non-motor symptoms is particularly important. AdipoRon (Ad), an adiponectin agonist, has demonstrated neuroprotective effects by suppressing neuroinflammatory responses and activating the AMPK/Sirt-1 signaling pathway. This study looked at the potential advantages and underlying mechanisms of intranasal Ad in a rat model of PD induced by 6-hydroxydopamine (6-OHDA). We found that Ad at doses of 1 and 10 µg for 21 days exhibited anxiolytic- and antidepressant effects in the open field (OF) test, elevated plus maze (EPM), sucrose splash test, and forced swimming test in a PD model caused by a unilateral 6-OHDA injection into the medial forebrain bundle (MFB). The Ad also lowered the levels of corticosterone in the blood, decreased inflammasome components (NLRP3, caspase 1, and IL-1β), and increased Sirt-1 protein levels in the prefrontal cortex (PFC) of PD rats. We conclude that Ad ameliorates anxious and depressive-like behaviors in the PD rat model through stimulating the AMPK/Sirt-1 signaling and blocking the NLRP3 inflammasome pathways in the PFC., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Achieving the optimal clinical outcome of mesenchymal stem cells (MSCs) is particularly dependent on fundamental understanding of therapeutic mechanisms. The current study was focused on the possible mechanisms by which rat bone marrow-derived mesenchymal stem cells (rBMMSCs) and/or conditioned media (CM) display broad immunomodulatory properties for ameliorating of asthma-related pathological changes. Male rats were divided equally into four experimental groups (n = 6): healthy rats received 50 μl PBS intravenously (group C), sensitized rats received 50 μl PBS intravenously (group OVA), sensitized rats received 50 μl CM intravenously (group OVA + CM), and sensitized rats received 50 μl PBS intravenously containing 2 × 10 6 rBMMSCs (group OVA + MSCs). After 2 weeks, the expression of interleukin (IL)-5, IL-12 and INF-γ, ICAM-1, and VCAM-1; pathological injuries; and the homing of MSCs into the lung tissues were assessed. Our results showed that systemic delivery of rBMMSCs, but not CM, returned the expression of IL-5, IL-12 and INF-γ, ICAM-1, and VCAM-1 and pathological injuries in the lung tissues of asthmatic groups to the near level of control group (p < 0.001 to p < 0.05). Moreover, rBMMSCs had potential to successfully recall to asthmatic niche in cell-administrated rats. However, no regulatory function was observed by MSC-CM. Collectively, our data notified the potency of MSCs in ameliorating OVA-mediated airway inflammation in a rat model of asthma presumably by regulating endothelial expression of leukocyte-selective cell adhesion molecules in lung tissue.

Many studies have shown a close relationship between obesity and asthma severity. In the present study, the effects of diet-induced obesity were examined on airway responsiveness to methacholine in addition to visfatin level in female Wistar rats' tracheae after sensitization with ovalbumin. The rats were divided into four groups: control with normal diet (ND), ovalbumin (OVA)-sensitized with normal diet (S + ND), high-fat diet (HFD), and OVA-sensitized with a high-fat diet (S + HFD). The animals were fed for 8 weeks with standard pelts or high-fat diet and then sensitized and challenged with OVA or saline for another 4 weeks. At the end of the study, the tracheae were isolated and assessed for airway responsiveness and visfatin protein levels. Diet-induced obesity groups developed increased weight and obesity indices (p < 0.001). After sensitization with OVA and diet-induced obesity, there were marked leftward shifts in methacholine concentration-response curves in S + HFD group compared to other groups. Also, maximum response was the highest (p < 0.05 to p < 0.001), EC 50 was the lowest (p < 0.05 to p < 0.001), and visfatin protein level was the highest (p < 0.05 to p < 0.01) in S + HFD. According to results, diet-induced obesity caused airway hyperresponsiveness to methacholine and enhanced visfatin protein levels in the tracheae of ovalbumin-sensitized female rats. Our results suggested that, in obese ovalbumin-sensitized conditions in female rats, the local production of adipocytokines, such as visfatin, may be increased, resulting in the deterioration of inflammation in lungs. This finding shows a possible mechanism for the altered phenotype in obesity-ovalbumin sensitization conditions in female rats.

Our aim in selecting an appropriate cell fraction and conditioned media (CM) was to achieve the suitable candidate for ameliorating long-term chronic asthmatic changes of respiratory tract. Thirty-six rats were classified into healthy and sensitized groups, which were further divided into three subgroups; rats received systemically 50 μl volume of PBS, CM, or 2 × 10 6 rat bone marrow-derived mesenchymal stem cells (rBMMSCs). Tracheal responsiveness (TR), immunologic responses, and recruitment of rBMMSCs into the lungs were evaluated. A high degree of TR and total WBC and percentages of eosinophils and neutrophils was significantly recorded in all sensitized groups rather than of controls (p < 0.001 to p < 0.05). Concurrently, a significant improvement of TR and eosinophil and neutrophil return toward normal levels was evident in sensitized rats receiving cells as compared to parallel asthmatic animals. Flow cytometric monitoring of lymphocyte subpopulation revealed a decrease in the number of CD3 + CD4 + and concurrent increase in CD3 + CD8 + in all sensitized rats as compared to control (p < 0.001 to p < 0.05). Noticeably, no significant modulatory effects of either cell or CM administration were achieved on the CD3 + CD4 + and CD3 + CD8 + populations in non-asthmatic rats. Corroborating our results, the number of CD3 + CD4 + tended to increase (p < 0.05) which coincided with a decreased manner of CD3 + CD8 + populations as compared to other asthmatic groups (p < 0.01 to p < 0.05). Moreover, stem cells could efficiently transmigrate to the lung parenchyma, albeit the dynamic of asthmatic changes stimulated the rate of recruited cells. Our study shed light on superior effects of mesenchymal stem cells, but not CM, in attenuating chronic asthmatic changes in the model of rat.