Effects of D-cycloserine on MPTP-induced behavioral and neurological changes: potential for treatment of Parkinson's disease dementia.
Glutamatergic dysfunction has been implicated in the neurodegeneration seen in Parkinson's disease (PD). Sub-chronic intraperitoneal injection with D-cycloserine (DCS), a partial agonist at the glycine binding site of the N-methyl-D-aspartate (NMDA) receptor, at dosages of 30, 100, or 200 mg/kg/day, was used to evaluate the role of NMDA receptors in neuronal and behavioral changes in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD rat model. Starting one day after intra-nigral infusion of MPTP, transient disturbance of motor function in the rotarod test was observed. This impairment spontaneously recovered to control levels 6 days after MPTP lesioning and DCS treatment facilitated recovery. MPTP lesioning also caused deficits in working memory and anxiety-like behavior in the T-maze and elevated plus-maze tests, respectively. Further, object recognition was disrupted in MPTP-lesioned rats, and interleukin-2 levels in the striatum, amygdala, and non-prefrontal cortex were increased, both changes being restored by DCS treatment. Furthermore, MPTP lesion-induced dopaminergic degeneration, microglial activation, and cell loss in the hippocampal CA1 area were all improved by DCS treatment. These results suggest that NMDA receptors are involved in PD-related neuronal and behavioral dysfunctions and that DCS may have clinical potential in the treatment of dementia associated with PD.
School of Psychology, Chung Shan Medical University Hospital, Chung Shan Medical University, Taiwan, ROC. yjho@csmu.edu.tw
Ying-Jui
YJ
Ho
Shih-Chun
SC
Ho
Cornelius Rainer
CR
Pawlak
Kuei-Ying
KY
Yeh
D000818:Animals; D001007:Anxiety / Q000523:psychology; D001921:Brain / Q000473:pathology; D003523:Cycloserine / Q000494:pharmacology*; D003704:Dementia / Q000188:drug therapy* / Q000209:etiology*; D006624:Hippocampus / Q000378:metabolism; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D007376:Interleukin-2 / Q000378:metabolism; D020267:MPTP Poisoning / Q000473:pathology* / Q000523:psychology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D017628:Microglia / Q000187:drug effects; D010300:Parkinson Disease / Q000150:complications*; D004856:Postural Balance / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D021641:Recognition, Psychology / Q000187:drug effects
D007376:Interleukin-2; D003523:Cycloserine