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Neurogenesis, the generation of new neurons, persists throughout the mammalian life span in the hippocampal dentate gyrus. Adult hippocampal neurogenesis may be severely affected in the course of PD, accounting for some of the neuropsychiatric symptoms such as depression and cognitive impairment. Two important PD\u2010related pathogenic factors have separately been attributed to contribute to both PD and adult hippocampal neurogenesis: dopamine depletion and accumulation of \u03b1\u2010synuclein (\u03b1\u2010syn). In the acute 1\u2010methyl\u20104\u2010phenyl\u20101,2,3,6\u2010tetrahydropyridine model, altered neurogenesis has been linked merely to a reduced dopamine level. Here, we seek to determine whether a distinct endogenous \u03b1\u2010syn expression pattern is associated, possibly contributing to the hippocampal neurogenic deficit. We observed a persistent reduction of striatal dopamine and a loss of tyrosine hydroxylase\u2010expressing neurons in the substantia nigra pars compacta in contrast to a complete recovery of tyrosine hydroxylase\u2010immunoreactive dopaminergic fibers within the striatum. However, dopamine levels in the hippocampus were significantly decreased. Survival of newly generated neurons was significantly reduced and paralleled by an accumulation of truncated, membrane\u2010associated, insoluble \u03b1\u2010syn within the hippocampus. Specifically, the presence of truncated \u03b1\u2010syn species was accompanied by increased activity of calpain\u20101, a calcium\u2010dependent protease. Our results further substantiate the broad effects of dopamine loss in PD\u2010susceptible brain nuclei, gradually involved in the PD course. Our findings also indicate a detrimental synergistic interplay between dopamine depletion and posttranslational modification of \u03b1\u2010syn, contributing to impaired hippocampal plasticity in PD. \u00a9 2015 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/jnr.23677","type":"journal-article","created":{"date-parts":[[2015,10,9]],"date-time":"2015-10-09T16:51:54Z","timestamp":1444409514000},"page":"62-73","source":"Crossref","is-referenced-by-count":35,"title":["Dopaminergic lesioning impairs adult hippocampal neurogenesis by distinct modification of \u03b1\u2010synuclein"],"prefix":"10.1002","volume":"94","author":[{"given":"Johannes C.M.","family":"Schlachetzki","sequence":"first","affiliation":[{"name":"Department of Molecular Neurology Friedrich\u2010Alexander\u2010Universit\u00e4t Erlangen\u2010N\u00fcrnberg Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Grimm","sequence":"additional","affiliation":[{"name":"Department of Molecular Neurology Friedrich\u2010Alexander\u2010Universit\u00e4t Erlangen\u2010N\u00fcrnberg Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zinayida","family":"Schlachetzki","sequence":"additional","affiliation":[{"name":"Department of Molecular Neurology Friedrich\u2010Alexander\u2010Universit\u00e4t Erlangen\u2010N\u00fcrnberg Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nada M.B.","family":"Ben Abdallah","sequence":"additional","affiliation":[{"name":"Department of Molecular Neurology Friedrich\u2010Alexander\u2010Universit\u00e4t Erlangen\u2010N\u00fcrnberg Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Ettle","sequence":"additional","affiliation":[{"name":"Department of Molecular Neurology Friedrich\u2010Alexander\u2010Universit\u00e4t Erlangen\u2010N\u00fcrnberg Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrizia","family":"V\u00f6hringer","sequence":"additional","affiliation":[{"name":"Department of CNS Diseases Research Germany Boehringer Ingelheim Pharma GmbH and Co. 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