Adeno-associated virus vector expressing nerve growth factor enhances cholinergic axonal sprouting after cortical injury in rats.

ABSTRACT

Nerve growth factor (NGF) is known to promote both the survival of cholinergic neurons after injury and the regeneration of damaged cholinergic axons. Recent evidence has implicated NGF in the regulation of cholinergic axonal sprouting by intact neurons projecting to the hippocampus of rats, sustaining a lesion of the entorhinal cortex. We explored the possibility that NGF may regulate this lesion-induced cholinergic sprouting by injecting recombinant adeno-associated virus (rAAV) vector expressing NGF and green fluorescent protein (GFP) into the dentate gyrus of rats that were subsequently given unilateral entorhinal lesions. Sprague Dawley rats were unilaterally injected with (1) rAAV vector expressing NGF and GFP or (2) rAAV vector expressing GFP. Fourteen days after injection, the animals received lesions of the entorhinal area ipsilateral to the virus injection. Four days after lesion, GFP expression and the septodentate sprouting response in the dentate gyrus were assessed. Optical densitometric analyses revealed a significant increase in acetylcholinesterase label (a marker for cholinergic septodentate sprouting) in the ipsilateral outer molecular layer of the dentate gyrus in rats injected with rAAV vector expressing NGF. Thus, NGF-expressing rAAV vector enhanced the sprouting response of intact cholinergic neurons after unilateral entorhinal lesions in rats.