Increased NGF proforms in aged sympathetic neurons and their targets

Area of Science:

• Neuroscience
• Molecular Biology
• Aging Research

Background:

• Target-derived neurotrophins, including nerve growth factor (NGF) and neurotrophin-3 (NT-3), are crucial for sympathetic neuron survival.
• Age-related neuronal atrophy affects sympathetic innervation in various peripheral targets.

Purpose of the Study:

• To investigate the roles of NGF and NT-3 in age-related sympathetic neuronal atrophy.
• To examine protein and transcript levels of NGF and NT-3 in sympathetic neurons and their targets during aging.

Main Methods:

• Quantitative analysis of NGF and NT-3 protein and mRNA levels.
• Comparison of neurotrophin expression in atrophied versus protected sympathetic nerve targets in aged subjects.

Main Results:

• A significant increase (up to 50-fold) in proNGF-B protein was observed in the superior cervical ganglion (SCG) and targets exhibiting sympathetic atrophy.
• ProNGF-B levels were decreased in the iris, a target with preserved sympathetic innervation in old age.
• NGF transcript alterations mirrored protein changes, while NT-3 showed less dramatic protein changes but varied transcript levels, with increases in the iris.

Conclusions:

• Dramatic increases in proNGF, particularly proNGF-B, alongside minimal NT-3 changes, suggest that dysregulation of NGF contributes to the loss of sympathetic innervation in aged peripheral targets.
• These findings highlight a potential mechanism for age-related sympathetic denervation, implicating NGF pathway alterations.