Parkinson’s disease (PD) is a severe and progressive motor disorder of the central nervous system. In PD the pigmented neurons, particularly the pars compacta of the substantia nigra, are susceptible to apoptosis. The pathophysiological mechanism of cell death in PD is unknown; however, some hypotheses have been developed. This is an area where much further research is needed to find possible neuroprotective agents. The neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) can damage dopamine systems in the brains of rodents, cats or monkeys, and is therefore widely used to model degenerative processes that underlie human PD. Various neurotrophic factors and peptides are prospective in prevention of neurodegeneration processes.

The aim of the present study was to investigate the influence of a new prolyl-tyrosin-containing dipeptide (PTCD) on MPTP-induced parkinsonian syndrome (PS) in mice. This compound was synthesized at the Institute of Pharmacology of RAMS, Russia. Two experimental series were carried out on 3- to 5-month-old C57Bl/6 male mice. The first experimental series demonstrated, that mice injected with MPTP only (30 mg kg^-1 I.P., twice daily, every 12 h for 7 days) did not survive for longer than 7 days. In mice injected with PTCD (2 mg kg^-1 I.P.) and MPTP (30 mg kg^-1 I.P.), survival at the 21st day was 100 %, and the animals did not show any significant symptoms of PS. Therefore, the neuropeptide protected mice against acute intoxication. In the second experimental series, mice injected with MPTP (25 mg kg^-1 I.P.) demonstrated some symptoms of PC by the 14th day: their motor activity decreased, the rigidity increased, the time spent motionless significantly increased, and the number of vertical movements significantly decreased on the 7th and 14th days. However, in MPTP-treated mice (25 mg kg^-1, I.P.) with PTDC (2 mg kg^-1, I.P.) investigated parameters did not differ from those in control animals. The development of PS was assessed by oligokinesia and muscle rigidity. Oligokinesia was estimated by changes in the motor activity and the number of vertical movements (rearings). Motor activity was monitored, allowing us to follow the dynamics, and the total motor activity of animals was measured in an automated regime for 3 min using the ‘Auto-Track’ program in opto-Varimex-3 system composed of a host controller (Apple-IIe), an interface box and 16 infrared beam-based activity sensors (Columbus Instruments, USA). Our previous data indicate that PTCD increased short-term of movement activity, the number of vertical movements, and speed of horizontal movements. It reduced muscular rigidity and time spent motionless. Signs of rigidity were also different: in MPTP-treated mice rigidity reached 0.86 points on the 7th day, and 2.29 points on the 14th day, while in mice subjected to I.P. administration of PTCD, rigidity was about 0.77 and 1.33 points, respectively. MPTP administration (daily, for 14 days) caused weight loss in experimental mice. It is supposed that PTDP has a neuroprotective effect. Preliminary data suggest that it is possible to protect DA-ergic neurons from MPTP neurotoxin with PTCD. The target for PTCD’s action could be neurotoxin intracellular transport. Further studies of PTCD’s mechanism of action in biochemical models are needed.

Research was supported by the RFBR grants 00-04-48391 and 02-04-06617.

All procedures accord with current local guidelines.