FASEB bioAdvancesPub Date : 2026-04-24eCollection Date: 2026-05-01DOI: 10.1096/fba.2025-00300
Tianyi Tao, Noelle Leon-Palmer, Sabrina DiPietro, Kristy L Townsend
{"title":"Methodological Challenges for Ablation of BMPR1A in Hypothalamic Tanycytes-A Cautionary Tale.","authors":"Tianyi Tao, Noelle Leon-Palmer, Sabrina DiPietro, Kristy L Townsend","doi":"10.1096/fba.2025-00300","DOIUrl":"10.1096/fba.2025-00300","url":null,"abstract":"<p><p>The hypothalamus coordinates energy-balance regulation and is also a neurogenic/plastic region in the adult brain. Tanycytes, a specialized population of radial glial-like cells lining the third ventricle, reside at the critical interface between the blood, cerebrospinal fluid, and hypothalamic parenchyma. This unique positioning enables them to sense metabolic and nutrient-derived signals, and to shuttle molecules between periphery and brain. Tanycytes can respond to glucose and lipids, as demonstrated by a calcium transient down their long processes that extend into the hypothalamic nuclei. Tanycytes are also capable of self-renewal and differentiation after brain injury, supporting their classification as putative neural stem cells in the adult hypothalamus. Bone morphogenetic protein (BMP) signaling regulates neuroplasticity and contributes to metabolic regulation, including appetite and sympathetic drive to adipose. We previously demonstrated that central administration of BMP7 suppresses appetite, and BMP receptor 1A (BMPR1A) in anorectic hypothalamic POMC neurons impacts appetite regulation. BMPR1A is also tightly and highly co-expressed in hypothalamic tanycytes. Here, we attempted to genetically inactivate BMPR1A in adult tanycytes to explore its functional roles. Using the Rax-CreER<sup>T2</sup>xBMPR1Aflox mouse line, we tested multiple routes of tamoxifen administration, as well as its metabolite, without success. Cre recombinase activity was successfully induced via dietary tamoxifen (shown by recombination of the BMPR1A locus and fluorescent reporter induction), but efficient BMPR1A knockout in adult tanycytes was not achieved. Similarly, adeno-associated viral (AAV)-mediated BMPR1A knockdown via the Dio2 promoter and intracerebroventricular delivery yielded limited efficiency, despite confirmed Cre activity indicated by reporter expression. We also observed a compensatory increase in BMPR1A in cells not targeted by these knock-out/knockdown systems, as we observed previously with POMC-Cre knockout of BMPR1A, indicating a responsiveness of the hypothalamic niche to manipulation of BMPR1A levels. Together, our findings support that Cre-driven reporter activity doesn't guarantee gene depletion, and demonstrate that current strategies for loss of function of BMPR1A in adult hypothalamic tanycytes remain technically challenging and require careful validation before interpretation of phenotypes. More efficient and reliable methods are required to elucidate the molecular signaling and functional roles of molecules expressed in adult tanycytes.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"8 ","pages":"e70107"},"PeriodicalIF":2.4,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13108591/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147766587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Paige L. Cole, Connor A. Stead, Jatin G. Burniston, Daniel J. Owens
{"title":"The Effects of Palmitoylethanolamide or Ibuprofen on the Abundance Profile and Synthesis Rate of Proteins in C2C12 Skeletal Myotubes","authors":"Paige L. Cole, Connor A. Stead, Jatin G. Burniston, Daniel J. Owens","doi":"10.1096/fba.2025-00286","DOIUrl":"10.1096/fba.2025-00286","url":null,"abstract":"<p>Palmitoylethanolamide (PEA) and ibuprofen (IBU) exert anti-inflammatory effects that may influence skeletal muscle adaptation; however, their impact on muscle proteome dynamics remains unclear. Dynamic proteome profiling was performed in differentiated C2C12 myotubes treated for 36 h with D<sub>2</sub>O and either vehicle control (VC), PEA (10 μM), or IBU (100 μM). Protein-specific fractional synthesis rates (FSR; 1541 proteins) and relative protein abundances at 36 h (3085 proteins) were quantified and compared between treatments and VC. Relative to VC, PEA increased synthesis rates of 101 proteins (<i>p</i> < 0.05), whereas 2 proteins exhibited reduced synthesis. IBU increased synthesis rates of 165 proteins and reduced 7 proteins relative to VC. Both PEA and IBU increased total ribosomal protein synthesis (~80% relative to VC) and increased the abundance of 40S ribosomal subunit proteins (~18% relative to VC at 36 h). In addition, IBU treatment was associated with greater abundance of proteins involved in muscle contraction and extracellular matrix organization, reduced abundance of proteins associated with carbohydrate metabolism (21 proteins), and increased abundance of proteins linked to lipid metabolic pathways (17 proteins), relative to VC. In contrast, PEA-induced abundance differences were largely restricted to ribosomal proteins. These findings demonstrate that PEA and IBU enhance ribosomal protein turnover relative to control, whereas IBU elicits broader treatment-associated proteome remodeling.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"8 4","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13104729/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147766570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kai Fushimi, Tasuku Kondo, Nodoka Ikegami, Mizuki Yamada, Sing Ying Wong, Mikako Sakamaki-Sunaga, Nobuhiro Hayashi
{"title":"Serum Proteomics of Multiple Menstrual Symptoms in Female Athletes: A Pilot Study","authors":"Kai Fushimi, Tasuku Kondo, Nodoka Ikegami, Mizuki Yamada, Sing Ying Wong, Mikako Sakamaki-Sunaga, Nobuhiro Hayashi","doi":"10.1096/fba.2026-00002","DOIUrl":"10.1096/fba.2026-00002","url":null,"abstract":"<p>Menstrual symptoms, including primary dysmenorrhea and premenstrual syndrome, are significant problems affecting women's health condition. However, their biological functions are still unclear. The objective of this study was to elucidate proteins related to menstrual symptoms with high-performance two-dimensional gel electrophoresis (2DE). Serum samples were collected once a week over 5 weeks. At the same time, 46 types of menstrual symptoms were evaluated using a menstrual distress questionnaire (MDQ) on a scale of 0–4 (0: not at all, closer to 4: very strongly). 2DE images were obtained from the serum of participants with continuous menstrual phases, including the luteal, menstrual, and follicular phases. Multiple regression analysis was conducted to identify proteins that change in response to the interaction between menstrual phase and menstrual symptoms. As a result, six symptoms were associated with specific proteins (muscle stiffness with serine protease-1; general aches and pains with junction plakoglobin; tension with transferrin, ceruloplasmin, and desmoglein; depression with kininogen-1; distractibility with dermcidin; take naps; stay in bed with transferrin and hemopexin). These results indicate that various menstrual symptoms may have different underlying mechanisms. Further research into these proteins may lead to novel understanding of menstrual symptoms and support more effective health management for women.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"8 4","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13096689/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147766596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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