The Medial Septum Is Insulin Resistant in the AD Presymptomatic Phase: Rescue by Nerve Growth Factor-Driven IRS
Alzheimer Disease
/ genetics
Animals
Cholinergic Neurons
/ drug effects
Disease Models, Animal
Insulin
/ pharmacology
Insulin Receptor Substrate Proteins
/ metabolism
Insulin Resistance
/ physiology
Mice
Mice, Transgenic
Nerve Growth Factor
/ pharmacology
Phosphorylation
/ drug effects
Rats
Rats, Wistar
Receptor, Insulin
/ metabolism
Septal Nuclei
/ drug effects
Signal Transduction
/ drug effects
Alzheimer’s disease
Basal forebrain cholinergic neurons
Brain insulin resistance
IRS1
NGF
Journal
Molecular neurobiology
ISSN: 1559-1182
Titre abrégé: Mol Neurobiol
Pays: United States
ID NLM: 8900963
Informations de publication
Date de publication:
Jan 2019
Jan 2019
Historique:
received:
18
01
2018
accepted:
23
03
2018
pubmed:
8
5
2018
medline:
14
6
2019
entrez:
9
5
2018
Statut:
ppublish
Résumé
Basal forebrain cholinergic neurons (BFCN) are key modulators of learning and memory and are high energy-demanding neurons. Impaired neuronal metabolism and reduced insulin signaling, known as insulin resistance, has been reported in the early phase of Alzheimer's disease (AD), which has been suggested to be "Type 3 Diabetes." We hypothesized that BFCN may develop insulin resistance and their consequent failure represents one of the earliest event in AD. We found that a condition reminiscent of insulin resistance occurs in the medial septum of 3 months old 3×Tg-AD mice, reported to develop typical AD histopathology and cognitive deficits in adulthood. Further, we obtained insulin resistant BFCN by culturing them with high insulin concentrations. By means of these paradigms, we observed that nerve growth factor (NGF) reduces insulin resistance in vitro and in vivo. NGF activates the insulin receptor substrate 1 (IRS
Identifiants
pubmed: 29736736
doi: 10.1007/s12035-018-1038-4
pii: 10.1007/s12035-018-1038-4
pmc: PMC6334735
doi:
Substances chimiques
Insulin
0
Insulin Receptor Substrate Proteins
0
Irs1 protein, mouse
0
Nerve Growth Factor
9061-61-4
Receptor, Insulin
EC 2.7.10.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
535-552Subventions
Organisme : MIUR FIRB
ID : RBAP10L8TY_004
Commentaires et corrections
Type : ErratumIn
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