PMID- 17971830 OWN - NLM STAT- MEDLINE DCOM- 20081008 LR - 20150311 IS - 0893-133X (Print) IS - 0893-133X (Linking) VI - 33 IP - 9 DP - 2008 Aug TI - Memantine upregulates BDNF and prevents dopamine deficits in SIV-infected macaques: a novel pharmacological action of memantine. PG - 2228-36 AB - N-methyl-D-aspartate (NMDA) receptor activation is involved in the pathogenetic cascades of neurodegenerative disorders including human immunodeficiency virus (HIV) dementia. Memantine, an uncompetitive NMDA receptor antagonist, which has been recently approved for the treatment of Alzheimer's disease, is being discussed as a potential adjunctive therapeutic substance for HIV dementia. We used simian immunodeficiency virus-infected rhesus macaques to assess the effects of memantine on brain dysfunction and brain pathology within 3-5 months after initial infection during early asymptomatic stage of disease. We had shown previously that within this time frame, marked changes were evident in the dopaminergic systems. Memantine was administered two weeks post infection, at peak viremia, in order to prevent early NMDA receptor activation due to immune mediators. We found that memantine prevented onset of dopamine deficits in the brains of SIV-infected macaques, without affecting early brain pathology or peripheral course of infection. Memantine specifically upregulated mRNA and protein expression of the neurotrophic factor brain-derived neurotrophic factor (BDNF), suggesting that the protective effect of memantine on dopamine function may be mechanistically remote from NMDA receptor antagonism. This novel pharmacological action of memantine may also be relevant for other neurodegenerative disorders and supports the involvement of neurotrophic factors in adult brain neuroprotection. FAU - Meisner, Falko AU - Meisner F AD - Institute of Virology and Immunobiology, University of Wurzburg, Germany. FAU - Scheller, Carsten AU - Scheller C FAU - Kneitz, Susanne AU - Kneitz S FAU - Sopper, Sieghart AU - Sopper S FAU - Neuen-Jacob, Eva AU - Neuen-Jacob E FAU - Riederer, Peter AU - Riederer P FAU - ter Meulen, Volker AU - ter Meulen V FAU - Koutsilieri, Eleni AU - Koutsilieri E CN - German Competence Network HIV/AIDS LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20071031 PL - England TA - Neuropsychopharmacology JT - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology JID - 8904907 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Excitatory Amino Acid Antagonists) RN - 0 (RNA, Messenger) RN - 102-32-9 (3,4-Dihydroxyphenylacetic Acid) RN - VTD58H1Z2X (Dopamine) RN - W8O17SJF3T (Memantine) RN - X77S6GMS36 (Homovanillic Acid) SB - IM MH - 3,4-Dihydroxyphenylacetic Acid/metabolism MH - Animals MH - Brain/drug effects/metabolism/pathology/virology MH - Brain-Derived Neurotrophic Factor/genetics/*metabolism MH - Disease Models, Animal MH - Dopamine/*metabolism MH - Excitatory Amino Acid Antagonists/*pharmacology/therapeutic use MH - Homovanillic Acid/metabolism MH - Humans MH - Macaca mulatta MH - Memantine/*pharmacology/therapeutic use MH - Oligonucleotide Array Sequence Analysis/methods MH - RNA, Messenger/metabolism MH - Simian Acquired Immunodeficiency Syndrome/drug therapy/*metabolism/pathology/virology MH - Up-Regulation/*drug effects MH - Viral Load/methods EDAT- 2007/11/01 09:00 MHDA- 2008/10/09 09:00 CRDT- 2007/11/01 09:00 PHST- 2007/11/01 09:00 [pubmed] PHST- 2008/10/09 09:00 [medline] PHST- 2007/11/01 09:00 [entrez] AID - 1301615 [pii] AID - 10.1038/sj.npp.1301615 [doi] PST - ppublish SO - Neuropsychopharmacology. 2008 Aug;33(9):2228-36. doi: 10.1038/sj.npp.1301615. Epub 2007 Oct 31.