Unexpected Neuroprotective Effects of Loganin on 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine-Induced Neurotoxicity and Cell Death in Zebrafish.

1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP), which induces the pathological characteristics of Parkinson's disease in rodents, also specifically targets dopaminergic neurons in zebrafish embryos and larvae. Loganin, a traditional Chinese drug, was reported to regulate immune function and possess anti-inflammatory and anti-shock effects. Here, we investigate the role of loganin in MPTP-induced Parkinson-like abnormalities in zebrafish. MPTP treatment-induced abnormal development, in larvae, such as pericardium edema, increased yolk color, yolk sac edema, and retarded yolk sac resorption, as well as defects in brain development. Loganin could block MPTP-induced defects, with little toxicity to the eggs. Results of whole mount in situ hybridization showed loganin prevented the loss of both dopaminergic neurons and locomotor activity, exhibited by larvae treated with MPTP. In addition, loganin significantly rescued MPTP-induced neurotoxicity on PC12 cells, possibly through the suppression of PI3K/Akt/mTOR axis and JNK signaling pathways. In conclusion, loganin blocks MPTP-induced neurotoxicity and abnormal development in zebrafish. J. Cell. Biochem. 118: 615-628, 2017. © 2016 Wiley Periodicals, Inc.

Acute toxicity of MPTP and MPP(+) in the brain of embryo and newborn mice.

1-Methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) causes damage to dopaminergic neurons in the nigrostriatal system, similar to that seen in Parkinson disease (PD). Recently, a few reports have confirmed neuroblastic apoptosis in the subventricular zone (SVZ) of adult C57BL/6J mice by i.p. injection of MPTP, and concluded that MPTP is also toxic to neuroblasts in the SVZ. While there have been many researches on the neurotoxicity of MPTP in adult mice, there have been only a few in fetal mice. In the present study, we assessed the toxicity of MPTP to embryonic and newborn mice after a single injection into pregnant or newborn mice. MPTP and 1-methyl-4-phenylpyridinium (MPP(+)), a metabolite of MPTP, caused loss of tyrosine hydroxylase (TH)-positive cells or fibers and increased apoptotic cells in embryonic and newborn mice. In addition, MPTP and MPP(+) induced a marked increase of apoptotic cells in the SVZ compared to the nigrostriatal system. The present results may indicate that MPTP and MPP(+) pass through the placenta and blood-brain barrier (BBB) and that a different mechanism may be involved in MPTP- or MPP(+)-induced toxicity in the SVZ and in the nigrostriatal system of embryonic and newborn mice.