title: MANF is widely expressed in mammalian tissues and differently regulated after ischemic and epileptic insults in rodent brain.
abstract: The mesencephalic astrocyte-derived neurotrophic factor (MANF) has been described as a survival factor for dopaminergic neurons in vitro, but its expression in mammalian tissues is poorly known. MANF and a homologous protein, the conserved dopamine neurotrophic factor (CDNF), form a novel evolutionary conserved family of neurotrophic factors. Here we used in situ hybridization and immunohistochemistry to characterize MANF expression in developing and adult mouse. MANF expression was widespread in the nervous system and non-neuronal tissues. In the brain, relatively high MANF levels were detected in the cerebral cortex, hippocampus and cerebellar Purkinje cells. After status epilepticus, Manf mRNA expression was transiently increased in the dentate granule cell layer of hippocampus, thalamic reticular nucleus and in several cortical areas. In contrast, following global forebrain ischemia changes in Manf expression were widespread in the hippocampal formation and more restricted in cerebral cortex. The widespread expression of MANF together with its evolutionary conserved nature and regulation by brain insults suggest that it has important functions both under normal and pathological conditions in many tissue types.
authors: Institute of Biotechnology, Viikki Biocenter, University of Helsinki, Helsinki, Finland.
authors: Päivi
authors: P
authors: Lindholm
authors: Johan
authors: J
authors: Peränen
authors: Jaan-Olle
authors: JO
authors: Andressoo
authors: Nisse
authors: N
authors: Kalkkinen
authors: Zaal
authors: Z
authors: Kokaia
authors: Olle
authors: O
authors: Lindvall
authors: Tõnis
authors: T
authors: Timmusk
authors: Mart
authors: M
authors: Saarma
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000033:anatomy & histology / Q000378:metabolism; D002545:Brain Ischemia / Q000378:metabolism*; D002460:Cell Line; D002470:Cell Survival; D004622:Embryo, Mammalian / Q000033:anatomy & histology / Q000502:physiology; D004827:Epilepsy / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D017403:In Situ Hybridization; D051379:Mice; D008969:Molecular Sequence Data; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D016415:Sequence Alignment; D014018:Tissue Distribution
chemical_list: C099695:MANF protein, human; C534671:MANF protein, mouse; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger