{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T12:34:06Z","timestamp":1787747646776,"version":"build-2784847793"},"reference-count":52,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2023,8,26]],"date-time":"2023-08-26T00:00:00Z","timestamp":1693008000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100001819","name":"International Rett Syndrome Foundation","doi-asserted-by":"publisher","award":["2022-FAR.L-CS_003 to S.C."],"award-info":[{"award-number":["2022-FAR.L-CS_003 to S.C."]}],"id":[{"id":"10.13039\/100001819","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,1,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Rett syndrome is a rare genetic neurodevelopmental disease, affecting 1 in over 10 000 females born worldwide, caused by de novo mutations in the X-chromosome-located methyl-CpG-binding protein 2 (MeCP2) gene. Despite the great effort put forth by the scientific community, a therapy for this devastating disease is still needed. Here, we tested the therapeutic effects of a painless mutein of the nerve growth factor (NGF), called human NGF painless (hNGFp), via a non-invasive intranasal delivery in female MeCP2+\/\u2212 mice. Of note, previous work had demonstrated a broad biodistribution of hNGFp in the mouse brain by the nasal delivery route.<\/jats:p>\n               <jats:p>We report that (i) the long-term lifelong treatment of MeCP2+\/\u2212 mice with hNGFp, starting at 2 months of age, increased the chance of survival while also greatly improving behavioural parameters. Furthermore, when we assessed the phenotypic changes brought forth by (ii) a short-term 1-month-long hNGFp-treatment, starting at 3 months of age (right after the initial presentation of symptoms), we observed the rescue of a well known neuronal target population of NGF, cholinergic neurons in the medial septum. Moreover, we reveal a deficit in microglial morphology in MeCP2+\/\u2212 mice, completely reversed in treated animals. This effect on microglia is in line with reports showing microglia to be a TrkA-dependent non-neuronal target cell population of NGF in the brain.<\/jats:p>\n               <jats:p>To understand the immunomodulatory activity of hNGFp, we analysed the cytokine profile after hNGFp treatment in MeCP2+\/\u2212 mice, to discover that the treatment recovered the altered expression of key neuroimmune-communication molecules, such as fractalkine.<\/jats:p>\n               <jats:p>The overall conclusion is that hNGFp delivered intranasally can ameliorate symptoms in the MeCP2+\/\u2212 model of Rett syndrome, by exerting strong neuroprotection with a dual mechanism of action: directly on target neurons and indirectly via microglia.<\/jats:p>","DOI":"10.1093\/brain\/awad282","type":"journal-article","created":{"date-parts":[[2023,8,26]],"date-time":"2023-08-26T22:28:45Z","timestamp":1693088925000},"page":"122-134","source":"Crossref","is-referenced-by-count":13,"title":["Reversal of neurological deficits by painless nerve growth factor in a mouse model of Rett syndrome"],"prefix":"10.1093","volume":"147","author":[{"given":"Alexia","family":"Tiberi","sequence":"first","affiliation":[{"name":"Institute of Neuroscience, CNR , 56124 Pisa , Italy"},{"name":"Bio@SNS Laboratory of Biology, Scuola Normale Superiore , 56126 Pisa , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Borgonovo","sequence":"additional","affiliation":[{"name":"Bio@SNS Laboratory of Biology, Scuola Normale Superiore , 56126 Pisa , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanna","family":"Testa","sequence":"additional","affiliation":[{"name":"Bio@SNS Laboratory of Biology, Scuola Normale Superiore , 56126 Pisa , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Pacifico","sequence":"additional","affiliation":[{"name":"Bio@SNS Laboratory of Biology, Scuola Normale Superiore , 56126 Pisa , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ajesh","family":"Jacob","sequence":"additional","affiliation":[{"name":"Bio@SNS Laboratory of Biology, Scuola Normale Superiore , 56126 Pisa , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariachiara","family":"Di Caprio","sequence":"additional","affiliation":[{"name":"Bio@SNS Laboratory of Biology, Scuola Normale Superiore , 56126 Pisa , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentino","family":"Totaro","sequence":"additional","affiliation":[{"name":"Bio@SNS Laboratory of Biology, Scuola Normale Superiore , 56126 Pisa , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariantonietta","family":"Calvello","sequence":"additional","affiliation":[{"name":"Bio@SNS Laboratory of Biology, Scuola Normale Superiore , 56126 Pisa , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonino","family":"Cattaneo","sequence":"additional","affiliation":[{"name":"Bio@SNS Laboratory of Biology, Scuola Normale Superiore , 56126 Pisa , Italy"},{"name":"Rita Levi-Montalcini European Brain Research Institute (EBRI) , 00161 Roma , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2670-8237","authenticated-orcid":false,"given":"Simona","family":"Capsoni","sequence":"additional","affiliation":[{"name":"Bio@SNS Laboratory of Biology, Scuola Normale Superiore , 56126 Pisa , Italy"},{"name":"Section of Human Physiology, Department of Neuroscience and Rehabilitation, University of Ferrara , 44121 Ferrara , 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