title: Both secreted and the cellular levels of BDNF attenuated due to tau hyperphosphorylation in primary cultures of cortical neurons.
abstract: Intracellular aggregation of hyperphosphorylated tau in neurofibrillary tangles (NFTs) is a major neuropathological hallmark of taupathies such as Alzheimer's disease. Okadaic acid (OKA) is a potent inhibitor of PP2A, leading to abnormal tau phosphorylation. Brain-derived neurotrophic factor (BDNF) is a neurotrophin that is selectively downregulated in AD. In this study, we investigated the effects of OKA induced tau hyperphosphorylation on secreted and cellular levels of BDNF in primary cortical neurons that were treated with 25nM OKA. Tau phosphorylation at threonine 231 (Thr231) sites was assessed by Western blot using antibodies against phospho-Thr231. Non-phosphorylated tau protein was detected with the Tau-1 antibody. Levels of BDNF secreted to the culture medium were determined by ELISA at the 8th and 24th hours of treatment. Cellular localization and protein expression of BDNF and tau were assessed by immunofluorescent labeling and fluorescent intensity measurements at 24h of treatment. Tau hyperphosphorylation was confirmed with increase in Thr231 and the decrease in Tau-1 signals after 8h of OKA treatment, compared with the control groups, secreted BDNF levels in the OKA-treated group were significantly lower after 24h of treatment but were not significantly different at 8h of treatment. BDNF immunoreactivity was seen in cytoplasm and neurites of the neurons in control group. BDNF immunoreactivity significantly decreased in the OKA treated group and this attenuation was significant especially at neurites. Our results suggest that the decrease in BDNF secretion and the BDNF expression might depend on the disruption of microtubule structure caused by tau hyperphosphorylation.
authors.affiliation: Department of Medical Biology, Cerrahpasa Faculty of Medicine, Istanbul University, Istanbul, Turkey. Electronic address: irem_aatasoy@yahoo.com.
authors.forename: İrem Lütfiye
authors.initials: İL
authors.lastname: Atasoy
authors.affiliation: Department of Medical Biology, Cerrahpasa Faculty of Medicine, Istanbul University, Istanbul, Turkey. Electronic address: erdincdu@yahoo.com.
authors.forename: Erdinç
authors.initials: E
authors.lastname: Dursun
authors.affiliation: Department of Medical Biology, Cerrahpasa Faculty of Medicine, Istanbul University, Istanbul, Turkey. Electronic address: duygugezenak@gmail.com.
authors.forename: Duygu
authors.initials: D
authors.lastname: Gezen-Ak
authors.affiliation: Department of Medical Biology, Cerrahpasa Faculty of Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: Derya
authors.initials: D
authors.lastname: Metin-Armağan
authors.affiliation: Department of Medical Biology, Cerrahpasa Faculty of Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: Melek
authors.initials: M
authors.lastname: Öztürk
authors.affiliation: Department of Medical Biology, Cerrahpasa Faculty of Medicine, Istanbul University, Istanbul, Turkey. Electronic address: drselmayilmazer@gmail.com.
authors.forename: Selma
authors.initials: S
authors.lastname: Yılmazer
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D003470:Culture Media; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D019319:Okadaic Acid / Q000494:pharmacology; D010766:Phosphorylation; D011247:Pregnancy; D061251:Primary Cell Culture; D051381:Rats; D017207:Rats, Sprague-Dawley; D024801:Tauopathies / Q000378:metabolism / Q000473:pathology; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D003470:Culture Media; D004791:Enzyme Inhibitors; D016875:tau Proteins; D019319:Okadaic Acid
keywords: Alzheimer’s disease; BDNF; Neurofibrillary tangles; Okadaic acid; Tau; Tauopathy