Intranasal delivery of BDNF rescues memory deficits in AD11 mice and reduces brain microgliosis.
AD11
Alzheimer's disease
BDNF
Neurodegeneration
Journal
Aging clinical and experimental research
ISSN: 1720-8319
Titre abrégé: Aging Clin Exp Res
Pays: Germany
ID NLM: 101132995
Informations de publication
Date de publication:
May 2021
May 2021
Historique:
received:
29
01
2020
accepted:
29
06
2020
pubmed:
18
7
2020
medline:
1
5
2021
entrez:
18
7
2020
Statut:
ppublish
Résumé
A decrease in brain-derived neurotrophic factor (BDNF), a neurotrophin essential for synaptic function, plasticity and neuronal survival, is evident early in the progression of Alzheimer's disease (AD), being apparent in subjects with mild cognitive impairment or mild AD, and both proBDNF and mature BDNF levels are positively correlated with cognitive measures. BDNF delivery is, therefore, considered of great interest as a potentially useful therapeutic strategy to contrast AD. Invasive BDNF administration has indeed been recently used in animal models of AD with promising results in rescuing memory deficits, synaptic density and cell loss. Here, we tested whether non-invasive intranasal administration of different BDNF concentrations after the onset of cognitive and anatomical deficits (6 months of age) could rescue neuropathological and memory deficits in AD11 mice, a model of NGF deprivation-induced neurodegeneration. In addition to AD hallmarks, we investigated BDNF effects on microglia presence in the brain of AD11 mice, since alterations in microglia activation have been associated with ageing-related cognitive decline and with the progression of neurodegenerative diseases, including AD. We found that intranasal delivery of 42 pmol BDNF (1 μM), but not PBS, was sufficient to completely rescue performance of AD11 mice both in the object recognition test and in the object context test. No further improvement was obtained with 420 pmol (10 μM) BDNF dose. The strong improvement in memory performance in BDNF-treated mice was not accompanied by an amelioration of AD-like pathology, Aβ burden, tau hyperphosphorylation and cholinergic deficit, but there was a dramatic decrease of CD11b immunoreactive brain microglia. These results reinforce the potential therapeutic uses of BDNF in AD and the non-invasive intranasal route as an effective delivery strategy of BDNF to the brain. They also strengthen the connection between neuroinflammation and neurodegenerative dementia and suggest microglia as a possible mediator of BDNF therapeutic actions in the brain.
Identifiants
pubmed: 32676979
doi: 10.1007/s40520-020-01646-5
pii: 10.1007/s40520-020-01646-5
pmc: PMC8081712
doi:
Substances chimiques
Amyloid beta-Peptides
0
Brain-Derived Neurotrophic Factor
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1223-1238Subventions
Organisme : Fondazione Pisa
ID : Train The Brain
Organisme : MIUR
ID : 2010N8PAA_006
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