Possible Role of Osteopathic Manipulation Treatment in Alleviation of Finasteride-Induced Dementia through Modulation of HOMER-3 Gene Methylation

Homer-3 gene is associated with neurological disorders that can affect cognitive function, including dementia. It is a protein that regulates AMPAR signaling in the hippocampus, which is involved in learning and memory. Craniosacral therapy, an osteopathic manipulative treatment, causes a reduction in symptoms associated with dementia and modulates the expression of genes associated with dementia including the HOMER-3 gene. Finasteride is a competitive inhibitor of 5-alpha-reductase (5-AR), an enzyme responsible for the conversion of testosterone into dihydrotestosterone (DHT) and used in the treatment of alopecia and prostatic enlargement. It induces atrophy of the hippocampus and causes neuropsychiatric disorders including dementia. In this work aimed at determining the methylation profile of finasteride on Leydig cells, we cultured human Leydig cells in the presence of 0.5 μM finasteride and performed whole-genome DNA methylation analysis using the NimbleGen Human DNA Methylation 3x720K Promoter Plus CpG Island Array and Ingenuity Pathway Analysis.Results showed that Finasteride induces dysregulation of several genes associated with neuropsychiatric disorders including the HOMER-3 gene implicated in dementia and modulated following craniosacral osteopathic manipulation. We therefore propose investigation of the effects of craniosacral osteopathic manipulative therapy on the methylation profile of HOMER-3 gene and its possible role in alleviation of neuropsychiatric symptoms linked to dementia following finasteride treatment. The findings will reveal the potential use of osteopathic manipulation therapy in treatment of finasteride-induced dementia through epigenetic modulation of HOMER-3 gene and possible amelioration of atrophic changes in hippocampus. This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.