The contribution of mouse models for basic and translational research at different levels is important to understand neurodegenerative diseases, including tauopathies, by studying the alterations in the corresponding mouse models in detail. Moreover, several studies demonstrated that pathological as well as behavioral changes are influenced by the sex. For this purpose, we performed an in-depth characterization of the behavioral alterations in the transgenic Tau-P301L mouse model. Sex-matched wild type and homozygous Tau-P301L mice were tested in a battery of behavioral tests at different ages. Tau-P301L male mice showed olfactory and motor deficits as well as increased Tau pathology, which was not observed in Tau-P301L female mice. Both Tau-P301L male and female mice had phenotypic alterations in the SHIRPA test battery and cognitive deficits in the novel object recognition test. This study demonstrated that Tau-P301L mice have phenotypic alterations, which are in line with the histological changes and with a sex-dependent performance in those tests. Summarized, the Tau-P301L mouse model shows phenotypic alterations due to the presence of neurofibrillary tangles in the brain.
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http://dx.doi.org/10.3390/biomedicines9091160 | DOI Listing |
Biomedicines
December 2024
Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, 12901 Bruce B Downs Blvd, Tampa, FL 33612, USA.
Alzheimer's disease (AD) is marked by amyloid-β plaques and hyperphosphorylated tau neurofibrillary tangles (NFTs), leading to cognitive decline and debilitating non-cognitive symptoms. This study aimed to evaluate compounds from four different classes in a short-term (7-day) study using transgenic tau mice to assess their ability to reduce non-cognitive symptoms. The best candidate was then evaluated for longer exposure to assess non-cognitive symptoms, cognition, and pathology.
View Article and Find Full Text PDFIBRO Neurosci Rep
December 2024
L&J Bio USA, Inc., Gaithersburg, MD 20878, USA.
Acta Neuropathol
September 2024
Microbiome Convergence Research Centre, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, 34141, Republic of Korea.
J Med Chem
August 2024
School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, 103 Wenhua Road Shenhe District, Shenyang, Liaoning 110016, P. R. China.
Targeting dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) has been verified to regulate the progression of tau pathology as a promising treatment for Alzheimer's disease (AD), while the research progress on DYRK1A inhibitors seemed to be in a bottleneck period. In this work, we identified () as the most potential DYRK1A inhibitor (IC = 0.68 nM) through rational design, systematic structural optimization, and comprehensive evaluation.
View Article and Find Full Text PDFFront Cell Neurosci
June 2024
Department of Pathology and Anatomical Sciences, University of Missouri School of Medicine, Columbia, MO, United States.
Mild traumatic brain injury (mTBI) resulting from low-intensity blast (LIB) exposure in military and civilian individuals is linked to enduring behavioral and cognitive abnormalities. These injuries can serve as confounding risk factors for the development of neurodegenerative disorders, including Alzheimer's disease-related dementias (ADRD). Recent animal studies have demonstrated LIB-induced brain damage at the molecular and nanoscale levels.
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