Overexpression of Nerve Growth Factor in the Hippocampus Induces Behavioral Changes in Rats with 192IgG-Saporin-Induced Cholinergic Deficit

Degeneration of septal cholinergic neurons caused by the immunotoxin 192IgG-saporin (SAP) is a model of the pathological state that occurs in Alzheimer's disease. We studied whether overexpression of nerve growth factor (NGF) in the hippo campus, where septal neurons send their projections, may reduce the consequences of this damage. A lentiviral suspension carrying a cassette with CMV-NGF-IRES-GFP or CMV-IRES-GFP (control, pCSC) was injected into both hippocampi. Control rats received an equivalent amount of PBS instead of SAP and the control virus construction PBS-pCSC. Analysis of choline acetyltransferase (ChAT) immunostaining showed that NGF overexpression in the hippocampus did not prevent the strong loss of ChAT-positive neurons in the septal area caused by the immunotoxin. In Open Field test, both SAP-NGF and SAP-pCSC-injected rats exhibited hyperactivity; in contrast, in the Y-maze SAP-induced hyperactivity was prevented by NGF overexpression. In the beam walking test, the NGF-expressing group of rats showed significant improvement of motor performance. Analysis of the acetylcholine esterase activity in the hippocampi, which we used as a marker of cholinergic function, revealed that the level of AChE was increased in the SAP-NGF group compared to SAP-pCSC. In conclusion, our data suggest that NGF overexpression in the hippocampus of rats may partly compensate some 192IgG-saporin-induced impairments related to cholinergic deficit.