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Transcriptomic and Proteomic Changes in the Brain Along with Increasing Phenotypic Severity in a Rat Model of Neonatal Hyperbilirubinemia

JP. Llido, G. Valerio, D. Křepelka, A. Dvořák, C. Bottin, F. Zanconati, JT. Regalado, A. Franceschi Biagioni, M. Qaisiya, L. Vítek, C. Tiribelli, S. Gazzin

. 2025 ; 26 (13) : . [pub] 20250628

Jazyk angličtina Země Švýcarsko

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/bmc25022593

Grantová podpora
FSE+ 2021/2027 n. 2023/3340 JTR, JPL were founded in part by DOST, in part by an internal grant from FIF. SG, CT, GV: Internal grant FIF. LV, AS and DK were supported by the grant MH CZ-DRO-VFN64165 from the Czech Ministry of Health. AFB was supported by Fondo Sociale Europeo Plus.

Kernicterus spectrum disorder is the permanent and highly disabling neurologic sequel of neonatal exposure to hyperbilirubinemia, presenting, among other symptoms, variable and untreatable motor disabilities. To search for potential biomolecular explanations, we used a Gunn rat colony exhibiting spontaneous hyperbilirubinemia and a large variability of motor deficits on a beam-walking test. Histological and microscopic analyses confirmed worsening damage in the cerebellum (Cll; hypoplasia, increased death of neurons, and disrupted astroglial structures) and parietal motor cortex (hCtx; increased cell sufferance and astrogliosis). Clustering and network analyses of transcriptomic data reveal rearrangement of the physiological expression patterns and signaling pathways associated with bilirubin neurotoxicity. Bilirubin content among hyperbilirubinemic (jj) animals is overlapped, which suggests that the amount of bilirubin challenge does not fully explain the tissue, transcriptomic, proteomic, and neurobehavioral alterations. The expression of nine genes involved in key postnatal brain development processes is permanently altered in a phenotype-dependent manner. Among them, Grm1, a metabotropic glutamatergic receptor involved in glutamate neurotoxicity, is consistently downregulated in both brain regions both at the transcriptomic and proteomic levels. Our results support the role of Grm1 and glutamate as biomolecular markers of ongoing bilirubin neurotoxicity, suggesting the possibility to improve diagnosis by 1H-MR spectroscopy.

Citace poskytuje Crossref.org

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