Vol.:(0123456789) 1 3 International Journal of Peptide Research and Therapeutics https://doi.org/10.1007/s10989-018-09803-1 The Efects of Leptin on Rat Brain Development; An Experimental Study Arzu Yay 1  · Gozde Ozge Onder 1  · Saim Ozdamar 2  · Anzel Bahadir 3  · Metin Aytekin 4  · Munevver Baran 5 Accepted: 26 December 2018 © Springer Nature B.V. 2019 Introduction Leptin has a crucial role in the development of the brain throughout the embryonic and neonatal stages. Leptin-def- cient mice have diminished total brain volume, weight, and DNA amount, which are redintegrated by the supplementa- tion of leptin (Ahima and Osei 2004; Steppan and Swick 1999). It has been determined that maternal leptin concen- tration was increased in transgenic skinny mice overexpress- ing leptin after birth, which was associated with a lower fetal body weight compared to wild type mice (Sagawa et al. 2002). These fndings suggest that leptin levels, from both the fetus and the mother, may be associated with the neona- tal growth and development (Udagawa et al. 2006). Leptin may serve as an important hormone for fetal growth. Its signaling may provide a nutritional sensing func- tion available from the mother to fetus during pregnancy (Masuzaki et al. 1997). In normal development, it has been detected in the blood of the umbilical cord at the 18th week of gestation, low levels until the 34th week, and dramati- cally increased toward the end of pregnancy (Harigaya et al. 1997). Therefore, the functions of the leptin have been antic- ipated in pregnancy (Ahima and Flier 2000; Henson and Castracane 2000). If the fetus encounters adverse factors, neuronal proliferation and axonal growth can be directly afected (Chen and Liu 2009). In a previous report, leptin was found to be elevated in fetuses with intrauterine growth retardation, suggesting a signifcant association between lep- tin concentration and gestational age (Cetin et al. 2000). It has also been suggested that leptin concentrations reached a peak in the second trimester between 22 and 27 weeks and remained high until birth (Sagawa et al. 2002). Interestingly during the fetal period neurons are rap- idly proliferating (Chen and Liu 2009) especially in the 10th–18th weeks of gestation. Leptin increases the prolif- erative activity of neural progenitor and neural stem cells. Therefore, many studies have eluded to a functional role of leptin in the alteration of both neural stem cells and glial progenitor cell diferentiation in vitro and in vivo within the hypothalamus. Also, these studies declared that leptin has neuroproliferative efects within the fetal cortex (Udagawa et al. 2006) through the maintenance of glial and multipotent stem cells. These investigations indicated that leptin must be required for the brain development throughout the fetal and neonatal stages of life (Udagawa et al. 2007). Nestin is a class VI intermediate flament protein that has been described as a general marker for both a wide a variety of progenitor cells and neural stem cells. It is closely and functionally aligned as a stem cell marker in neurogenesis (Andressen et al. 2001). Also, this protein constitutes heli- cal bundles in neuroepithelial stem/progenitor cells in the growing CNS of embryonal rats and humans (Chinnaiyan * Arzu Yay arzu.yay38@gmail.com Gozde Ozge Onder gozdekorkmaz@erciyes.edu.tr Saim Ozdamar sozdamar@pau.edu.tr Anzel Bahadir anzelbahadir@duzce.edu.tr Metin Aytekin Aytekim@ccf.org Munevver Baran m.baran@erciyes.edu.tr 1 Department of Histology and Embryology, Faculty of Medicine, Erciyes University, Kayseri, Turkey 2 Department of Histology and Embryology, Faculty of Medicine, Pamukkale University, Kayseri, Turkey 3 Department of Biophysics, Faculty of Medicine, Duzce University, Duzce, Turkey 4 Department of Pathobiology/Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA 5 Department of Pharmaceutical Basic Science, Faculty of Pharmacy, Erciyes University, Kayseri, Turkey