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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\u00a0months 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\u00a0pmol BDNF (1\u00a0\u03bcM), 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\u00a0pmol (10\u00a0\u03bcM) BDNF dose. The strong improvement in memory performance in BDNF-treated mice was not accompanied by an amelioration of AD-like pathology, A\u03b2 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.<\/jats:p>","DOI":"10.1007\/s40520-020-01646-5","type":"journal-article","created":{"date-parts":[[2020,7,16]],"date-time":"2020-07-16T06:29:16Z","timestamp":1594880956000},"page":"1223-1238","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["Intranasal delivery of BDNF rescues memory deficits in AD11 mice and reduces brain microgliosis"],"prefix":"10.1007","volume":"33","author":[{"given":"Chiara","family":"Braschi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"Capsoni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Narducci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Poli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriele","family":"Sansevero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rossella","family":"Brandi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lamberto","family":"Maffei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonino","family":"Cattaneo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2718-2284","authenticated-orcid":false,"given":"Nicoletta","family":"Berardi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,7,16]]},"reference":[{"key":"1646_CR1","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1097\/00002093-200304000-00002","volume":"17","author":"A Wimo","year":"2003","unstructured":"Wimo A, Winblad B, Aguero-Torres H et al (2003) The magnitude of dementia occurrence in the world. 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