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Neural progenitor cells are protected against MPTP by MAO-B inhibitors
Xi Jun He1, Koji Uetsuka, Hiroyuki Nakayama
1Department of Veterinary Pathology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-Ku, Tokyo 113-8657, Japan. aaa37172@mail.goo.ne.jp
Abstract:
Neurotoxic effects of MPTP on the nigrostriatal dopaminergic system are thought to be initiated by 1-methyl-4-phenylpyridinium (MPP+), a metabolite formed by the monoamine oxidase (MAO)-B-mediated oxidation of MPTP. We previously reported that the administration of MPTP induced apoptosis in migrating neuroblasts (neural progenitor cells, NPCs) in adult mice. To determine whether MAO-B is also involved in the neurotoxicity of MPTP to NPCs, this study looked at the effects of MAO B inhibitors, R(-)-deprenyl (deprenyl) and N-(2-aminoethyl)-4-chlorobenzamide (Ro 16-6491), both of which protect the dopaminergic system against MPTP. Few apoptotic cells were found in saline- or MAO-B inhibitor-treated animals but MPTP markedly induced apoptosis in the subventricular zone (SVZ) and rostral migratory stream (RMS) after 1 day. When mice were pretreated with deprenyl or Ro 16-6491, not only nigrostriatal dopamine levels but also NPCs were significantly protected against MPTP. In addition, MPTP-induced apoptosis was found in both juvenile (postnatal 21 days) and older (12 months old) mice, suggesting NPCs to be different from the dopamine system, which has been thought to exhibit age-dependent susceptibility to MPTP.
Insights
Monoamine oxidase B (MAO-B) inhibitors protect neural progenitor cells (NPCs) from MPTP-induced neurotoxicity. Pretreatment with MAO-B inhibitors prevented apoptosis in NPCs, demonstrating their protective role in MPTP neurotoxicity.
Area of Science:
- Neuroscience
- Neuropharmacology
- Cell Biology
Background:
- 1-methyl-4-phenylpyridinium (MPP+), a metabolite of MPTP, is known to cause neurotoxic effects on the nigrostriatal dopaminergic system.
- Previous research indicated that MPTP administration induces apoptosis in migrating neural progenitor cells (NPCs) in adult mice.
Purpose of the Study:
- To investigate the involvement of monoamine oxidase B (MAO-B) in the neurotoxicity of MPTP towards NPCs.
- To evaluate the protective effects of MAO-B inhibitors against MPTP-induced NPC apoptosis.
Main Methods:
- Administration of MPTP to mice, with and without pretreatment with MAO-B inhibitors (R(-)-deprenyl and Ro 16-6491).
- Assessment of apoptosis in NPCs within the subventricular zone (SVZ) and rostral migratory stream (RMS).
- Measurement of nigrostriatal dopamine levels.
Main Results:
- MPTP markedly induced apoptosis in NPCs in the SVZ and RMS.
- Pretreatment with MAO-B inhibitors significantly protected both nigrostriatal dopamine levels and NPCs against MPTP.
- MPTP-induced NPC apoptosis was observed in both juvenile and older mice, unlike the age-dependent susceptibility of the dopamine system.
Conclusions:
- MAO-B plays a significant role in MPTP-induced neurotoxicity to NPCs.
- MAO-B inhibitors offer substantial protection to NPCs against MPTP.
- NPCs exhibit a different susceptibility profile to MPTP compared to the dopamine system, as they are not age-dependent.
