| First Author | Depboylu C | Year | 2015 |
| Journal | J Neurochem | Volume | 133 |
| Issue | 4 | Pages | 590-7 |
| PubMed ID | 25581060 | Mgi Jnum | J:221815 |
| Mgi Id | MGI:5641593 | Doi | 10.1111/jnc.13026 |
| Citation | Depboylu C, et al. (2015) Systemically administered neuregulin-1beta1 rescues nigral dopaminergic neurons via the ErbB4 receptor tyrosine kinase in MPTP mouse models of Parkinson's disease. J Neurochem 133(4):590-7 |
| abstractText | Previously, we demonstrated that systemically injected extracellular domain of neuregulin-1beta1 (Nrg1beta1), a nerve growth and differentiation factor, passes the blood-brain barrier and rescues dopaminergic neurons of substantia nigra in the 6-hydroxydopamine-mouse model of Parkinson's disease (PD). Here, we studied the effects of peripherally administered Nrg1beta1 in another toxin-based mouse model of PD. For this purpose, (i) nigrostriatal pathway injury was induced by treatment of adult wild-type mice with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in acute and subchronic paradigms; and (ii) Nrg1beta1 or saline (control) were administered 1 h before each MPTP injection. We found that Nrg1beta1 significantly reduced the loss of nigral dopaminergic neurons in both intoxication paradigms (7 days post-injection). However, Nrg1beta1 did not reverse MPTP-induced decrease in dopamine levels and dopaminergic fibers in the striatum. We also show that MPTP conversion to its toxic metabolite 1-methyl-4-phenylpyridinium as well as levels of dopamine transporter, mediating intracellular uptake of 1-methyl-4-phenylpyridinium, are unaffected by Nrg1beta1. Finally, neuroprotective properties of Nrg1beta1 on nigral dopaminergic neurons are specifically mediated by ErbB4 as revealed through the study of ErbB4 knockout mice. In conclusion, systemically administered Nrg1beta1 protects midbrain dopaminergic neurons against this PD-related toxic insult. Thus, Nrg1beta1 may have a benefit in the treatment of PD patients. Previously, we demonstrated that systemically administered neuregulin-1beta1 (Nrg1beta1) passes the blood-brain barrier, phosphorylates ErbB4 receptors and elevates dopamine (DA) levels in the nigrostriatal system of healthy mice. Nrg1beta1 protects nigral DAergic neurons in the 6-hydroxydopamine (6-OHDA) mouse model of Parkinson's disease (PD). Here, we show that Nrg1beta1 rescues nigral DAergic neurons also against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced cell death. ErbB4 expression is essential for the neuroprotective effect of Nrg1beta1 on midbrain DAergic neurons. Nrg1beta1 might be beneficial in PD treatment. |
