Widespread cortical expression of MANF by AAV serotype 7: Localization and protection against ischemic brain injury
| Autor: | Chao Liu, Johan Peränen, Yun Wang, Mikko Airavaara, Barry J. Hoffer, Brandon K. Harvey, Doug B. Howard, Matt J. Chiocco, Shengyun Fang, Katie L. Zuchowski |
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| Rok vydání: | 2010 |
| Předmět: |
Male
Pathology medicine.medical_specialty viruses Genetic Vectors Ischemia Motor Activity Pharmacology Article Brain Ischemia Rats Sprague-Dawley Brain ischemia 03 medical and health sciences 0302 clinical medicine Developmental Neuroscience Neurotrophic factors Animals Humans Medicine Nerve Growth Factors Cells Cultured Cerebral dopamine neurotrophic factor 030304 developmental biology 0303 health sciences biology business.industry Cerebral infarction Proteins Infarction Middle Cerebral Artery Genetic Therapy Recovery of Function Dependovirus medicine.disease Rats Disease Models Animal Nerve growth factor medicine.anatomical_structure Neurology Cerebral cortex biology.protein business 030217 neurology & neurosurgery Neurotrophin |
| Zdroj: | Experimental Neurology. 225:104-113 |
| ISSN: | 0014-4886 |
| DOI: | 10.1016/j.expneurol.2010.05.020 |
| Popis: | Mesencephalic astrocyte-derived neurotrophic factor (MANF) is a secreted protein which reduces endoplasmic reticulum (ER) stress and has neurotrophic effects on dopaminergic neurons. Intracortical delivery of recombinant MANF protein protects tissue from ischemic brain injury in vivo. In this study, we examined the protective effect of adeno-associated virus serotype 7 encoding MANF in a rodent model of stroke. An AAV vector containing human MANF cDNA (AAV-MANF) was constructed and verified for expression of MANF protein. AAV-MANF or an AAV control vector was administered into three sites in the cerebral cortex of adult rats. One week after the vector injections, the right middle cerebral artery (MCA) was ligated for 60 min. Behavioral monitoring was conducted using body asymmetry analysis, neurological testing, and locomotor activity. Standard immunohistochemical and western blotting procedures were conducted to study MANF expression. Our data showed that AAV-induced MANF expression is redistributed in neurons and glia in cerebral cortex after ischemia. Pretreatment with AAV-MANF reduced the volume of cerebral infarction and facilitated behavioral recovery in stroke rats. In conclusion, our data suggest that intracortical delivery of AAV-MANF increases MANF protein production and reduces ischemic brain injury. Ischemia also caused redistribution of AAV-mediated MANF protein suggesting an injury-induced release. |
| Databáze: | OpenAIRE |
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