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neurodegenerative disorders like Alzheimers disease.that affect the central nervous system typically result in pathology throughout the brain; thus,gene therapy strategies need to achieve widespread delivery.With the rapid development of neuroscience research,new methods are needed for neuroscientists to quickly and easily manipulate gene expression in the mouse brain.The method of direct intracranial delivery of virally-encoded transgenes into the neonatal mouse brain approach offers a timely method for manipulating gene expression in the mouse brain that is fast,easy,and far less expensive than traditional germline engineering.It is previously reported that although intraventricular injection of the neonatal mouse brain with adeno-associated virus serotype 2(AAV2)results in dispersed gene delivery,many brain structures were poorly transduced.This limitation may be overcome by using different AAV serotypes because the capsid proteins use different cellular receptors for entry,which may allow enhanced global targeting of the brain.We tested this with AAV5 and AAV9 vectors during the first 12-24 hr of neonatal mice after birth.AAV5 showed very limited brain transduction after neonatal injection,even though it has different transduction patterns than AAV9 in adult brain injections.In contrast,AAV9 vectors showed robust widespread transduction.In the majority of structures,AAV9 transduced many more cells than AAV8.Both vectors transduced mostly neurons,indicating that differential expression of receptors on the surfaces of neurons occurs in the developing brain.We have previously reported that mir let7c can reduce beta amyloid protein production by activating BACE2.A comprehensive analysis of AAV9-treated brains from APP/PSEN mice showed reversal of pathology in all areas of the brain for at least 1 year,demonstrating that the AAV of this serotype and experimental strategy is therapeutically effective for treating global neurodegenerative disorders.