Pandamooz S., Bozkurt N. M., Ünal G., Salehi M. S.
European College of Neuropsychopharmacology, Milan, İtalya, 21 - 24 Eylül 2024, ss.666, (Özet Bildiri)
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Yayın Türü:
Bildiri / Özet Bildiri
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Doi Numarası:
10.1016/j.nsa.2024.105389
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Basıldığı Şehir:
Milan
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Basıldığı Ülke:
İtalya
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Sayfa Sayıları:
ss.666
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Erciyes Üniversitesi Adresli:
Evet
Özet
Background: The complexities of the human brain pose significant challenges in neuropsychiatric disorder research due to limitations in current model systems. However, advancements in patient-derived stem cell technology and insights into the role of the oxytocin (OXT) system provide new avenues for exploration. While animal models have contributed valuable insights into OXT and its receptor (OXTR), patient-derived stem cell models related to this neuropeptide and its receptor are lacking. Based on prior research that identified OXTR expression in migratory hair follicle stem cells (HFSCs) and validated their functionality upon OXT stimulation, this study aims to investigate potential differences in OXTR expression in HFSCs from a valproic acid (VPA)-induced rat model of autism.
Methods: In this study, VPA (at dose of 500 mg/kg) was administered to Wistar rats on prenatal day 12.5 to induce autistic-like behaviors. HFSCs were subsequently obtained from the bulge explant of whisker pad follicles from both genders of normal and autistic groups. We examined the number of bulges containing migrated stem cells at the end of the initial cell subculture phase, providing crucial insights into the migratory behavior of these stem cells under autistic conditions. We then characterized the migrated stem cells from both groups using immunostaining against well-established HFSC markers, Nestin and SOX-10, to confirm their identity. Subsequently, we evaluated the expression of OXTR at the gene level between the experimental groups by qRT-PCR to assess the impact of autism at molecular level.
Results: Our findings revealed notable differences in the number of bulges containing migrated stem cells between the control and VPA-induced groups. In the control group, 83% of females and 45% of males exhibited migrated stem cells, whereas in the VPA-induced group, these percentages decreased to 39% in females and 17% in males. Additionally, all groups demonstrated expression of Nestin and SOX-10 at the protein level, that are main cellular markers of HFSCs. Notably, the expression of OXTR in the male autistic group was significantly lower compared to the corresponding male normal groups (P<0.01), while no significant difference was detected between female rats in the normal and autistic groups (P=0.93).
Conclusions: our study highlights the potential of patient-derived stem cell models in elucidating the molecular mechanisms underlying neuropsychiatric disorders. By utilizing a valproic acid-induced rat model of autism, we demonstrated alterations in the migration and OXTR expression of hair follicle stem cells, suggesting a dysregulation within the oxytocinergic system. These findings underscore the importance of investigating OXTR expression in HFSCs as a potential biomarker for autism spectrum disorders, potentially promising advancements in diagnostic and therapeutic paradigms for these conditions. Moreover, our findings suggest that males may have a greater susceptibility to the brain disturbances connected with autism. This discovery emphasizes the importance of taking gender differences into account in both research efforts and medical treatment, advocating for a more detailed approach to comprehending and managing the wide range of ASD symptoms.