TOXOPATHOLOGICAL EFFECT OF 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE ON THE BRAIN AND GASTROINTESTINAL TRACT OF C57BL/6 MICE: POTENTIAL PROTECTIVE ROLE OF N-ACETYLSEROTONIN

The current study tried to explore the neuroprotective effects of N-Acetylserotonin (NAS) against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced toxopathological derangements in C57BL/6 mice. Fifty male mice were assigned into 5 groups (10 each): control, MPTP (1 wk), MPTP (3 wk), MPTP and NAS, and NAS. MPTP was given at a dose of 25 mg/kg b.w., intraperitoneally (i.p.), for 5 consecutive days. NAS was given at a dose of 20 mg/kg b.w., i.p., on the 3rd day post-MPTP treatment till the 28th day. At the end of each treatment, body weight gain and gastrointestinal (GIT) functions were assessed, and specimens from the brain, colon, stomach, and adrenal glands were obtained and processed for histopathological analysis. MPTP induced a significant reduction in body weight gain compared to controls, and on the other hand, concomitant treatment with MPTP and NAS significantly ameliorated gain loss in body weight, compared to the MPTP group. Neither MPTP nor concomitant treatment with MPTP and NAS altered GIT functions as evaluated by one hour stool collection test and the solid gastric emptying test. Histopathologically, MPTP markedly induced neuronal cell loss in the substantia nigra (SN), degeneration of hippocampal neurons, and neuronal degeneration and microglial activation in some sporadic brain areas. Moreover, MPTP resulted in decreasing colon thickness, gastric mucosal alterations, and mild vacuolation of adrenal zona fasciculata (ZF) cells. Co-treatment with MPTP and NAS significantly alleviated these pathological alterations. In conclusion, NAS is protective against MPTP-induced pathological alterations in the brain, colon, stomach and adrenal glands in C57BL/6 mice relevant to PD.

Jilin University
Assiut University
Arish University