Intrahippocampal Adeno-Associated Virus–Mediated Overexpression of Nerve Growth Factor Reverses 192IgG-Saporin–Induced Impairments of Hippocampal Plasticity and Behavior

One of the aspects of Alzheimer disease is loss of cholinergic neurons in the basal forebrain, which leads to development of cognitive impairment. Here, we used a model of cholinergic deficit caused by immunotoxin 192IgG-saporin to study possible beneficial effects of adeno-associated virus (AAV)–mediated overexpression of nerve growth factor (NGF) in the hippocampus of rats with cholinergic deficit. Suspension of recombinant AAV carrying control cassette or cassette with NGF was injected into both hippocampi of control rats or rats with cholinergic deficit induced by intraseptal injection of 192IgG-saporin. Analysis of choline acetyltransferase (ChAT) immunostaining showed that NGF overexpression in the hippocampus did not prevent strong loss of ChAT-positive neurons in the septal area caused by the immunotoxin. Induction of cholinergic deficit in the hippocampus led to impairments in Y-maze and beam-walking test but did not affect behavioral indices in the T-maze, open field test, and inhibitory avoidance training. NGF overexpression in the rats with cholinergic deficit restored normal animal behavior in Y-maze and beam-walking test. Recording of field excitatory postsynaptic potentials in vivo in the hippocampal CA1 area showed that induction of cholinergic deficit decreased magnitude of long-term potentiation (LTP) and prevented a decrease in paired-pulse ratio after LTP induction, and NGF overexpression reversed these negative changes in hippocampal synaptic characteristics. The beneficial effect of NGF was not associated with compensatory changes in the number of cells that express NGF receptors TrkA and NGFR in the hippocampus and medial septal area. NGF overexpression also did not prevent a 192IgG-saporin–induced decrease in the activity of acetylcholine esterase in the hippocampus. We conclude that NGF overexpression in the hippocampus under conditions of cholinergic deficit induces beneficial effects which are not related to maintenance of cholinergic function.

Inagaki & Ross (in press): Giving targeted versus untargeted support

Objective. Giving support contributes to the link between social ties and health, however, the neural mechanisms are not known. Giving support in humans may rely on neural regions implicated in parental care in animals. The current studies, therefore, assess the contribution of parental care-related neural regions to giving support in humans and, as a further theoretical test, examine whether the benefits of giving targeted support to single, identifiable individuals in need extends to giving untargeted support to larger societal causes. Methods. For Study 1 (n = 45, M age = 21.98 (3.29), 69% females), participants completed a giving support task followed by an emotional faces task in the fMRI scanner. For Study 2 (n = 382, M age=43.03 (7.28), 52% females), participants self-reported on their giving support behavior and completed an emotional faces task in the fMRI scanner. Results. In Study 1, giving targeted (vs. untargeted) support resulted in greater feelings of social connection and support effectiveness. Further, greater septal area (SA) activity, a region centrally involved in parental care in animals, to giving targeted support was associated with less right amygdala activity to an emotional faces task (r=-.297, 95% CI=[-.547, -.043]). Study 2 replicated and extended this association to show that self-reports of giving targeted support were associated with less amygdala activity to a different emotional faces task, even when adjusting for other social factors (r=-.105, 95% CI=[-.200, -.011]). Giving untargeted support was not related to amygdala activity in either study.