Andrés Benito, PolFlores de los Heros, ÁfricaBusquet-Areny, SaraCarmona Murillo, MargaritaAusín, KarinaCartas Cejudo, PazLachén Montes, MercedesRío Fernández, José Antonio delFernández Irigoyen, JoaquínSantamaría, EnriqueFerrer, Isidro (Ferrer Abizanda)2023-05-292023-05-292023-03-311661-6596https://hdl.handle.net/2445/198569Transcriptomics and phosphoproteomics were carried out in the cerebral cortex of B6.Cg-Mapttm1(EGFP)Klt (tau knockout: tau-KO) and wild-type (WT) 12 month-old mice to learn about the effects of tau ablation. Compared with WT mice, tau-KO mice displayed reduced anxiety-like behavior and lower fear expression induced by aversive conditioning, whereas recognition memory remained unaltered. Cortical transcriptomic analysis revealed 69 downregulated and 105 upregulated genes in tau-KO mice, corresponding to synaptic structures, neuron cytoskeleton and transport, and extracellular matrix components. RT-qPCR validated increased mRNA levels of col6a4, gabrq, gad1, grm5, grip2, map2, rab8a, tubb3, wnt16, and an absence of map1a in tau-KO mice compared with WT mice. A few proteins were assessed with Western blotting to compare mRNA expression with corresponding protein levels. Map1a mRNA and protein levels decreased. However, β-tubulin III and GAD1 protein levels were reduced in tau-KO mice. Cortical phosphoproteomics revealed 121 hypophosphorylated and 98 hyperphosphorylated proteins in tau-KO mice. Deregulated phosphoproteins were categorized into cytoskeletal (n = 45) and membrane proteins, including proteins of the synapses and vesicles, myelin proteins, and proteins linked to membrane transport and ion channels (n = 84), proteins related to DNA and RNA metabolism (n = 36), proteins connected to the ubiquitin-proteasome system (UPS) (n = 7), proteins with kinase or phosphatase activity (n = 21), and 22 other proteins related to variegated pathways such as metabolic pathways, growth factors, or mitochondrial function or structure. The present observations reveal a complex altered brain transcriptome and phosphoproteome in tau-KO mice with only mild behavioral alterations.19 p.application/pdfengcc-by (c) Andrés Benito, Pol et al., 2023https://creativecommons.org/licenses/by/4.0/Escorça cerebralRatolins (Animals de laboratori)Teixit nerviósNeuronesCerebral cortexMice (Laboratory animals)Nerve tissueNeuronsinfo:eu-repo/semantics/article7334122023-05-29info:eu-repo/semantics/openAccess37047532