ORIGINAL ARTICLE 17β-estradiol modulates NGF and BDNF expression through ERβ mediated ERK signaling in cortical astrocytes Jaldeep M. Langhnoja 1 & Lipi K. Buch 1 & Prakash P. Pillai 1 Received: 8 March 2018 /Accepted: 25 July 2018 # Institute of Molecular Biology, Slovak Academy of Sciences 2018 Abstract 17β-estradiol is known to exert neurotrophic and neuroprotective effects through classical estrogen receptors [ERs], ERα and ERβ, on a variety of cell types either by genomic or non-genomic actions. The actions of estradiol on glial cells are important to maintain metabolic functions of the nervous system. Astrocytes are considered to be active participants in brain activity because of their ability to release growth factors, including neurotrophins. Present in vitro studies show that 17β-estradiol modulates NGF and BDNF expression in time-dependent manner and ERK acts as secondary messenger for estradiol’ s action. 17β-estradiol is involved in survival of cortical astrocytes. In conclusion, this study indicates vital role of ERβ mediated ERK signalling for regulation of NGF and BDNF expression along with cell viability of cortical astrocytes which further confirms the role of ERs, particularly ERβ in glial cells’ functions and viability. Keywords BDNF . ERK . 17β-estradiol . NGF Abbreviations E2 17β-estradiol ERs Estradiol Receptors ERα Estradiol Receptor alpha ERβ Estradiol Receptor beta NGF Nerve growth factor BDNF Brain derived neurotrophic factor NT3 Neurotrophins 3 NT4/5 Neurotrophins 4/5 ERK Extracellular regulated kinase MEK Mitogen activated protein kinase GFAP Glial fibrillary acidic protein Introduction 17β-estradiol (E2), a steroid hormone plays a diverse role at cellular and molecular levels in brain cells. Secretion of this hormone is mainly by the ovaries, brain and fat tissue through aromatization of testosterones. During development, estradiol regulates cell proliferation, differentiation and survival in the brain (MacLusky et al. 1987; TORAN-ALLERAND 2005). Estradiol regulates neural plasticity and dendritic spine densi- ty in the brain regions (Gould et al. 1990; Matsumoto and Arai 1981; Woolley et al. 1990). Two distinct estrogen receptors (ERs), ER alpha (ERα) and ER beta (ERβ) are distributed in the brain regions (McEwen et al. 1997; Mitra et al. 2003; Register et al. 1998; Shughrue et al. 1997) and located in nucleus as well as in cytoplasm, and this localization decides estradiol’ s mode of action (Lee and McEwen 2001). Nucleus- initiated receptors’ signaling activate new gene transcription by association with estrogen response elements (EREs) in the DNA (Nelson and Bulun 2001), also called direct genomic action while membrane associated receptors cooperate with growth factor receptors or G-protein-coupled receptors to ac- tivate kinase cascades through indirect genomic action (Hammes and Levin 2007; Levin 2005; Thomas et al. 2005; Vasudevan and Pfaff 2007). Post receptor activation, estradiol is involved in many of the cascades such as induction of anti-apoptotic gene expres- sion, maintenance of intracellular calcium homeostasis, pro- moting antioxidant activity and modulating actions of neurotrophins (Lee and McEwen 2001). The major focus in the present study is to elucidate the role of estradiol in neurotrophin expression modulation. Neurotrophins are a family of proteins that are important for neuronal * Prakash P. Pillai pillaippp@gmail.com; prakash.pillai-zoo@msubaroda.ac.in 1 Division of Neurobiology, Department of Zoology, The Maharaja Sayajirao University of Baroda, Vadodara, Gujarat, India Biologia https://doi.org/10.2478/s11756-018-0099-1