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Our previous work using\n                      <jats:italic>Cntnap2<\/jats:italic>\n                      <jats:sup>-\/-<\/jats:sup>\n                      and\n                      <jats:italic>Shank3<\/jats:italic>\n                      <jats:sup>\u03944\u201322<\/jats:sup>\n                      ASD mouse models implicated dysregulated nitric oxide (NO) signaling in ASD-related behaviors, which were improved by inhibition of neuronal nitric oxide synthase (nNOS) with 7-Nitroindazole (7-NI). However, the molecular mechanisms linking NO signaling to ASD pathology remain poorly defined.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed mass spectrometry-based global proteomic profiling of cortical tissue from both mouse models under baseline conditions and following 7-NI treatment. Systems biology and bioinformatics analyses were used to identify differentially expressed proteins, enriched pathways, and treatment-responsive networks. Cross-model comparisons were performed to assess molecular convergence and overlap with human ASD-risk genes. Behavioral and biochemical assessments were reanalyzed to evaluate ASD-like phenotypes and treatment effects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Treatment with 7-NI improved ASD-like behavioral deficits in\n                      <jats:italic>Cntnap2<\/jats:italic>\n                      and\n                      <jats:italic>Shank3<\/jats:italic>\n                      mutant mice, including increased sociability and reduced anxiety-like behavior. 7-NI was also associated with attenuation of cortical protein alterations across synaptic, neuronal, and metabolic pathways, shifting subsets of dysregulated proteins toward wild-type expression levels. Despite distinct genetic mutations, the two models converged at the protein and pathway levels, including treatment-responsive proteins encoded by high-confidence human ASD risk genes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Limitations<\/jats:title>\n                    <jats:p>Analyses were restricted to cortical tissue; additional brain regions may reveal complementary mechanisms. Mass spectrometry may underrepresent low-abundance proteins; larger sample sizes could improve statistical power. Potential off-target effects of 7-NI should also be considered.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These findings show that nNOS inhibition improves ASD-like behaviors and is associated with partial normalization of altered cortical proteins across two genetically distinct ASD mouse models that display convergent molecular changes, including proteins encoded by high-confidence ASD risk genes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13229-026-00716-1","type":"journal-article","created":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T17:06:49Z","timestamp":1776704809000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Nitric oxide inhibition ameliorates cortical proteomic changes in the Cntnap2-\/- and Shank3\u03944\u201322 mouse models of autism spectrum disorder"],"prefix":"10.1186","volume":"17","author":[{"given":"Wisam","family":"Bazbaz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maryam","family":"Kartawy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Igor","family":"Khaliulin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haitham","family":"Amal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,20]]},"reference":[{"issue":"1","key":"716_CR1","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1038\/s41572-019-0138-4","volume":"6","author":"C Lord","year":"2020","unstructured":"Lord C, Brugha TS, Charman T, Cusack J, Dumas G, Frazier T, Jones EJH, Jones RM, Pickles A, State MW, et al. 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