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BDNF levels are lower in multiple brain regions of Mecp2-deficient mice, and experimentally increasing BDNF levels improve atypical phenotypes in Mecp2 mutant mice. Due to the low blood-brain barrier permeability of BDNF itself, we tested the effects of LM22A-4, a brain-penetrant, small-molecule ligand of the BDNF receptor TrkB (encoded by Ntrk2), on dendritic spine density and form in hippocampal pyramidal neurons and on behavioral phenotypes in female Mecp2 heterozygous (HET) mice. A 4-week systemic treatment of Mecp2 HET mice with LM22A-4 restored spine volume in MeCP2-expressing neurons to wild-type (WT) levels, whereas spine volume in MeCP2-lacking neurons remained comparable to that in neurons from female WT mice. Female Mecp2 HET mice engaged in aggressive behaviors more than WT mice, the levels of which were reduced to WT levels by the 4-week LM22A-4 treatment. These data provide additional support to the potential usefulness of novel therapies not only for RTT but also to other BDNF-related disorders.<\/jats:p>","DOI":"10.1242\/dmm.050612","type":"journal-article","created":{"date-parts":[[2024,5,24]],"date-time":"2024-05-24T06:02:40Z","timestamp":1716530560000},"source":"Crossref","is-referenced-by-count":11,"title":["A small-molecule TrkB ligand improves dendritic spine phenotypes and atypical behaviors in female Rett syndrome mice"],"prefix":"10.1242","volume":"17","author":[{"given":"Destynie","family":"Medeiros","sequence":"first","affiliation":[{"name":"School of Medicine 1 Department of Neurobiology , , , Birmingham, AL 35294 , USA"},{"name":"University of Alabama at Birmingham 1 Department of Neurobiology , , , Birmingham, AL 35294 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Ayala-Baylon","sequence":"additional","affiliation":[{"name":"School of Medicine 1 Department of Neurobiology , , , 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