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, suggesting that decreased NGF receptor stimulation may be one factor contributing to neuronal dysfunction with aging. Other studies have suggested that aging may be associated with impaired intracellular responses to NGF. Because aging-associated neuronal dysfunction contributes to morbidity and mortality 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 and neuronal survival in short-term cultures (0-96 h) of dorsal root ganglion (DRG) neurons from aged (>22 months) Fisher 344 x Brown Norway F1 hybrid rats, 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 due to an increased rate of apoptotic cell death. DRG neurons from aged animals also exhibited significantly decreased whole cell, high-threshold voltage-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 neurons.
Hall
K E
KE
Department of Internal Medicine, Ann Arbor VA Medical Center, University of Michigan, GRECC 11G, D-318, Ann Arbor, MI 48105-2399, USA. kehall@umich.edu
Sheng
H C
HC
Srinivasan
S
S
Spitsbergen
J M
JM
Tuttle
J B
JB
Steers
W D
WD
Wiley
J W
JW
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects* / Q000502:physiology; D016895:Culture Media, Serum-Free / Q000494:pharmacology*; D005727:Ganglia, Spinal / Q000166:cytology; D020287:In Situ Nick-End Labeling; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D020932:Nerve Growth Factor / Q000494:pharmacology*; D016501:Neurites / Q000187:drug effects / Q000502:physiology*; D009475:Neurons, Afferent / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D018408:Patch-Clamp Techniques; D051381:Rats; D011914:Rats, Inbred BN; D011916:Rats, Inbred F344
D020746:Calcium Channels, L-Type; D016895:Culture Media, Serum-Free; D020932:Nerve Growth Factor; D002118:Calcium