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Intranasal delivery of BDNF rescues memory deficits in AD11 mice and reduces brain microgliosis
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...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer International Publishing
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8081712/ https://www.ncbi.nlm.nih.gov/pubmed/32676979 http://dx.doi.org/10.1007/s40520-020-01646-5 |
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author | Braschi, Chiara Capsoni, Simona Narducci, Roberta Poli, Andrea Sansevero, Gabriele Brandi, Rossella Maffei, Lamberto Cattaneo, Antonino Berardi, Nicoletta |
author_facet | Braschi, Chiara Capsoni, Simona Narducci, Roberta Poli, Andrea Sansevero, Gabriele Brandi, Rossella Maffei, Lamberto Cattaneo, Antonino Berardi, Nicoletta |
author_sort | Braschi, Chiara |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8081712 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Springer International Publishing |
record_format | MEDLINE/PubMed |
spelling | pubmed-80817122021-05-05 Intranasal delivery of BDNF rescues memory deficits in AD11 mice and reduces brain microgliosis Braschi, Chiara Capsoni, Simona Narducci, Roberta Poli, Andrea Sansevero, Gabriele Brandi, Rossella Maffei, Lamberto Cattaneo, Antonino Berardi, Nicoletta Aging Clin Exp Res Original Article 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. Springer International Publishing 2020-07-16 2021 /pmc/articles/PMC8081712/ /pubmed/32676979 http://dx.doi.org/10.1007/s40520-020-01646-5 Text en © The Author(s) 2020 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Original Article Braschi, Chiara Capsoni, Simona Narducci, Roberta Poli, Andrea Sansevero, Gabriele Brandi, Rossella Maffei, Lamberto Cattaneo, Antonino Berardi, Nicoletta Intranasal delivery of BDNF rescues memory deficits in AD11 mice and reduces brain microgliosis |
title | Intranasal delivery of BDNF rescues memory deficits in AD11 mice and reduces brain microgliosis |
title_full | Intranasal delivery of BDNF rescues memory deficits in AD11 mice and reduces brain microgliosis |
title_fullStr | Intranasal delivery of BDNF rescues memory deficits in AD11 mice and reduces brain microgliosis |
title_full_unstemmed | Intranasal delivery of BDNF rescues memory deficits in AD11 mice and reduces brain microgliosis |
title_short | Intranasal delivery of BDNF rescues memory deficits in AD11 mice and reduces brain microgliosis |
title_sort | intranasal delivery of bdnf rescues memory deficits in ad11 mice and reduces brain microgliosis |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8081712/ https://www.ncbi.nlm.nih.gov/pubmed/32676979 http://dx.doi.org/10.1007/s40520-020-01646-5 |
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