Treatment of aged rat sensory neurons in short-term, serum-free culture with nerve growth factor reverses the effect of aging on neurite outgrowth, calcium currents, and neuronal survival

Impaired NGF production and release has been documented in aged animals, su ggesting that decreased NGF receptor stimulation may be one factor contribu ting to neuronal dysfunction with aging. Other studies have suggested that aging may be associated with impaired intracellular responses to NGF. Becau se aging-associated neuronal dysfunction contributes to morbidity and morta lity in the geriatric population, it is important to determine whether the effects of aging on sensory neuron function and survival are reversible. In the present study, we observed significantly decreased neurite outgrowth a nd neuronal survival in short-term cultures (0-96 h) of dorsal root ganglio n (DRG) neurons from aged (>22 months) Fisher 344XBrown Norway Fl hybrid ra ts, compared to young (4-6 month) and middle-aged (14 month) animals. From 24 to 96 h in culture, diminished survival of aged neurons appeared to be d ue to an increased rate of apoptotic cell death. DRG neurons from aged anim als also exhibited significantly decreased whole cell, high-threshold volta ge-dependent calcium currents, with a larger proportion of L-type current, compared to youthful and middle-aged animals. Treatment of aged DRG neurons with NGF restored neurite outgrowth, neuronal survival and calcium current amplitude and subtype distribution to those observed in youthful DRG neuro ns. (C) 2001 Elsevier Science B.V. All rights reserved.