Long-Term Protective Effects of AAV9-Mesencephalic Astrocyte-Derived Neurotrophic Factor Gene Transfer in Parkinsonian Rats.

Long-Term Protective Effects of AAV9-Mesencephalic Astrocyte-Derived Neurotrophic Factor Gene Transfer in Parkinsonian Rats. Exp Neurol. 2017 Jan 25;: Authors: Hao F, Yang C, Chen SS, Wang YY, Zhou W, Hao Q, Lu T, Hoffer B, Zhao LR, Duan WM, Xu QY Abstract Intrastriatal injection of mesencephalic astrocyte-derived neurotrophic factor (MANF) protein has been shown to provide neuroprotective and neurorestorative effects in a 6-hydroxydopamine (6-OHDA) - lesioned rat model of Parkinson's disease. Here, we used an adeno-associated virus serotype 9 (AAV9) vector to deliver the human MANF (hMANF) gene into the rat striatum 10 days after a 6-OHDA lesion to examine long-term effects of hMANF on nigral dopaminergic neurons and mechanisms underlying MANF neuroprotection. Intrastriatal injection of AAV9-hMANF vectors led to a robust and widespread expression of the hMANF gene in the injected striatum up to 24 weeks. Increased levels of hMANF protein were also detected in the ipsilateral substantia nigra. The hMANF gene transfer promoted the survival of nigral dopaminergic neurons, regeneration of striatal dopaminergic fibers and an upregulation of striatal dopamine levels, resulting in a long-term improvement of rotational behavior up to 16 weeks after viral injections. By using SH-SY5Y cells, we found that intra- and extracellular application of MANF protected cells against 6-OHDA-induced toxicity via inhibiting the endoplasmic reticulum stres...
Source: Experimental Neurology - Category: Neurology Authors: Tags: Exp Neurol Source Type: research