Retrograde axonal transport of BDNF and proNGF diminishes with age in basal forebrain cholinergic neurons

NEUROBIOLOGY OF AGING

卷:84

Article

Shekari, Arman¹  Fahnestock, Margaret¹ 

[1] McMaster Univ, Dept Psychiat & Behav Neurosci, 1280 Main St West, Hamilton, ON L8S 4K1, Canada

关键词: Axonal transport;    Neurotrophins;    Neurodegeneration;    Basal forebrain;    Alzheimer's disease;    Trk receptors;   

DOI  :  10.1016/j.neurobiolaging.2019.07.018

来源: Elsevier

【 摘 要 】

Basal forebrain cholinergic neurons (BFCNs) are critical for learning and memory and degenerate early in Alzheimer's disease (AD). BFCNs depend for their survival and function on nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), which are retrogradely transported from BFCN targets. Age is the greatest risk factor for developing AD, yet the influence of age on BFCN axonal transport is poorly understood. To model aging, embryonic rat basal forebrain or cortical neurons were cultured in microfluidic chambers. Senescence-associated beta-galactosidase staining indicated an aging phenotype only in BFCNs cultured for 18+ days in vitro. BDNF axonal transport impairments were observed exclusivley in aged BFCNs. BFCNs displayed robust proNGF transport, which also diminished with in vitro age. The expression of NGF receptor tropomyosin-related kinase-A and BDNF receptor tropomyosin-related kinase-B also decreased significantly with in vitro age in BFCNs only. These results suggest a unique vulnerability of BFCNs to age-induced transport deficits. These deficits, coupled with the reliance of BFCNs on neurotrophin transport, may explain their vulnerability to age-related neurodegenerative disorders like AD. (C) 2019 Elsevier Inc. All rights reserved.

【 授权许可】

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