Abstract
We studied the effects of infusion of nerve growth factor (NGF) into the hippocampus and entorhinal cortex of male Wistar rats (250-300 g, N = 11-13 per group) on inhibitory avoidance retention. In order to evaluate the modulation of entorhinal and hippocampal NGF in short- and long-term memory, animals were implanted with cannulae in the CA1 area of the dorsal hippocampus or entorhinal cortex and trained in one-trial step-down inhibitory avoidance (foot shock, 0.4 mA). Retention tests were carried out 1.5 h or 24 h after training to measure short- and long-term memory, respectively. Immediately after training, rats received 5 microl NGF (0.05, 0.5 or 5.0 ng) or saline per side into the CA1 area and entorhinal cortex. The correct position of the cannulae was confirmed by histological analysis. The highest dose of NGF (5.0 ng) into the hippocampus blocked short-term memory (P < 0.05), whereas the doses of 0.5 (P < 0.05) and 5.0 ng (P < 0.01) NGF enhanced long-term memory. NGF administration into the entorhinal cortex improved long-term memory at the dose of 5.0 ng (P < 0.05) and did not alter short-term memory. Taken as a whole, our results suggest a differential modulation by entorhinal and hippocampal NGF of short- and long-term memory.
Highlights
Neurotrophins, traditionally viewed as trophic proteins for neuronal survival and differentiation, have recently emerged as a new class of neuromodulators for synaptic transmission and plasticity, in the central nervous system [1]
A similar Nerve growth factor (NGF) infusion has a beneficial effect on performance in the Morris water maze after fluid-percussion brain injury, which is accompanied by a sparing of cholinergic septal neurons [7]
NGF can be retrogradely transported by cholinergic neurons in the basal forebrain, preventing death of axotomized septal neurons, as well as reversing the atrophy of these neurons observed in aging rats [8]
Summary
Neurotrophins, traditionally viewed as trophic proteins for neuronal survival and differentiation, have recently emerged as a new class of neuromodulators for synaptic transmission and plasticity, in the central nervous system [1]. Walz et al [9] reported that infusion of NGF into the CA1 region of hippocampus at doses of 0.5 and 5.0 ng per side at 0 and 120 min after inhibitory avoidance enhanced long-term memory. They described a significant enhancement of MAPK activity in hippocampal slices after NGF infusion (5.0 ng).
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