Cerebral dopamine neurotrophic factor alleviates Aβ25-35-induced endoplasmic reticulum stress and early synaptotoxicity in rat hippocampal cells

Alzheimer's disease (AD) is an age-related progressive neurodegenerative disease, and early stage AD is characterized by synaptic dysfunction generally ascribed to soluble oligomers of amyloid-beta (A(3). Neurotrophic factors are promising for AD treatment and are integrally involved in neuronal growth, survival and maintenance. Cerebral dopamine neurotrophic factor (CDNF) was recently discovered to have beneficial effects on long-term memory. The present study explored the synaptoprotective effects of CDNF in A beta-treated primary hippocampal cells. Immunofluorescent analysis of synaptophysin and postsynaptic density protein 95 (PSD95) puncta densities in the group of pretreatment with CDNF before A beta exposure revealed significant improvements compared to A beta group. In addition, pretreatment with CDNF reduced the expression levels of endoplasmic reticulum (ER) stress-related proteins, including Bip (also known as GRP78), phosphorylation of eukaryotic translation initiation factor 2 subunit a (peIF2 alpha), phosphorylation of c-Jun N-terminal kinase (pJNK), and cleaved caspase 3, which are increased by A beta treatment at early stage. Our results revealed protective effects of CDNF on A beta-induced synaptotoxicity and ER stress, implying that CDNF may protect against A beta-induced synaptotoxicity through suppression of ER stress. CDNF could be a potential drug candidate for early AD treatment. (C) 2016 Elsevier Ireland Ltd. All rights reserved.