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An increase in brain\u2010derived neurotrophic factor (BDNF) expression may be one of the molecular signals associated to compensatory and plastic responses occurring in basal ganglia during presymptomatic PD. In the present study, we used in vivo microdialysis, semiquantitative reverse transcriptase\u2013polymerase chain reaction, and immunohistochemistry to study N\u2010methyl\u2010<jats:sc>D<\/jats:sc>\u2010aspartic acid (NMDA) receptor regulation of BDNF expression in substantia nigra (SN) of adult rats after partial lesioning of the nigrostriatal DA pathway with unilateral striatal injections of 6\u2010hydroxydopamine (6\u2010OHDA). A time\u2010dependent partial decrease of striatal DA tissue content as well as parallel and gradual increases in extracellular glutamate and aspartate levels in SN were found 1 to 7 days after unilateral 6\u2010OHDA intrastriatal injection. Instead, the number of tyrosine hydroxylase\u2013immunoreactive (IR) cells in the ipsilateral SN pars compacta remained statistically unchanged after neurotoxin injection. Intrastriatal administration of 6\u2010OHDA also produced an early and transient augmentation of pan\u2010BDNF, exon II\u2013BDNF, and exon III\u2013BDNF transcripts in the ipsilateral SN. The pan\u2010BDNF and exon II\u2013BDNF transcript increases were completely abolished by the prior systemic administration of MK\u2010801, a selective antagonist of NMDA receptors. MK\u2010801 also blocked the increase in BDNF\u2010IR cells in SN observed 7 days after unilateral 6\u2010OHDA intrastriatal injections. Our findings suggest that a coupling between glutamate release, NMDA receptor activation, and BDNF expression may exist in the adult SN and represent an important signal in this midbrain nucleus triggered in response to partial DA loss occurring in striatal nerve endings during presymptomatic PD. \u00a9 2009 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jnr.22063","type":"journal-article","created":{"date-parts":[[2009,3,26]],"date-time":"2009-03-26T18:23:11Z","timestamp":1238091791000},"page":"2308-2318","source":"Crossref","is-referenced-by-count":16,"title":["NMDA receptors mediate an early up\u2010regulation of brain\u2010derived neurotrophic factor expression in substantia nigra in a rat model of presymptomatic Parkinson's 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