Compromise of cortical proNGF maturation causes selective retrograde atrophy in cholinergic nucleus basalis neurons.
Neurobiol Aging
; 67: 10-20, 2018 07.
Article
in En
| MEDLINE
| ID: mdl-29609077
ABSTRACT
The degeneration of basal forebrain cholinergic neurons (BFCNs) in Alzheimer's disease (AD) contributes to cognitive impairment. Nerve growth factor (NGF) secreted in the cerebral cortex is necessary for the phenotypic maintenance of BFCNs. AD is associated with disturbances in NGF metabolism, leading to reduced mature NGF levels and to an accumulation of its precursor, proNGF. We previously described that, in rats, this neurotrophic imbalance is sufficient to induce a loss of cortical cholinergic synapses. In the present study, we investigated whether this neurotrophic imbalance can produce an AD-like retrograde degeneration of BFCNs. Using a combination of retrograde labeling and quantitative cell imaging, we could demonstrate that inhibiting cortical proNGF maturation results in an atrophy of BFCNs, a downregulation of the NGF receptors p75 neurotrophin receptor and tropomyosin receptor kinase A, and a reduction in choline acetyltransferase protein expression. The transient increase in sortilin levels and the sustained colocalization with p75 neurotrophin receptor suggest a participation of proNGF in this degenerative process. This study demonstrates that impairments in the extracellular maturation of proNGF are sufficient to cause a somatodendritic retrograde degeneration of the BFCNs.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Protein Precursors
/
Cholinergic Neurons
/
Basal Forebrain
/
Nerve Growth Factors
Type of study:
Etiology_studies
Limits:
Animals
Language:
En
Journal:
Neurobiol Aging
Year:
2018
Type:
Article
Affiliation country:
Canada