ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2014
Reversible behavioral phenotypes in a conditional mouse model of TDP-43 proteinopathies.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed.
- Region-specific features of early glial activation and Aquaporin-4 dysregulation in conditional mouse models of TDP-43 proteinopathies.Discovery immunology · 2026Article
- Synaptic changes contribute to persistent extra-motor behaviour deficits in amyotrophic lateral sclerosis.Acta neuropathologica communications · 2025Article
- Network Dysfunction Precedes Neurodegeneration in a dox-Regulatable TDP-43 Mouse Model of ALS-FTD.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- CK1δ/ε-mediated TDP-43 phosphorylation contributes to early motor neuron disease toxicity in amyotrophic lateral sclerosis.Acta neuropathologica communications · 2024Article
- Mitigation of TDP-43 toxic phenotype by an RGNEF fragment in amyotrophic lateral sclerosis models.Brain : a journal of neurology · 2024Article
- Loss of GDE2 leads to complex behavioral changes including memory impairment.Behavioral and brain functions : BBF · 2024Article
- Elevated PDGF-BB from Bone Impairs Hippocampal Vasculature by Inducing PDGFRβ Shedding from Pericytes.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Intrathecal Injection of the Secretome from ALS Motor Neurons Regulated for miR-124 Expression Prevents Disease Outcomes in SOD1-G93A Mice.Biomedicines · 2022Article
- Protein synthesis modulation as a therapeutic approach for amyotrophic lateral sclerosis and frontotemporal dementia.Neural regeneration research · 2022Review
- Targeting iNOS Alleviates Early Brain Injury After Experimental Subarachnoid Hemorrhage via Promoting Ferroptosis of M1 Microglia and Reducing Neuroinflammation.Molecular neurobiology · 2022Article
- The progress inSmall GTPases · 2022Review
- Phenotypic diversity in ALS and the role of poly-conformational protein misfolding.Acta neuropathologica · 2021Review
- Automated home-cage for the evaluation of innate non-reflexive pain behaviors in a mouse model of inflammatory pain.Scientific reports · 2021Article
- Cytoplasmic Expression of the ALS/FTD-Related Protein TDP-43 Decreases Global Translation BothFrontiers in cellular neuroscience · 2020Article
- Liver CEBPβ Modulates the Kynurenine Metabolism and Mediates the Motility for Hypoxia-Induced Central Fatigue in Mice.Frontiers in physiology · 2019Article
- Prion-Like Propagation of Protein Misfolding and Aggregation in Amyotrophic Lateral Sclerosis.Frontiers in molecular neuroscience · 2019Article
- Suppression of Conditional TDP-43 Transgene Expression Differentially Affects Early Cognitive and Social Phenotypes in TDP-43 Mice.Frontiers in genetics · 2019Article
- Neurons selectively targeted in frontotemporal dementia reveal early stage TDP-43 pathobiology.Acta neuropathologica · 2019Article
- Disease-modifying effects of metabolic perturbations in ALS/FTLD.Molecular neurodegeneration · 2018Review
- Reply: TDP-43 mutations increase HNRNP A1-7B through gain of splicing function.Brain : a journal of neurology · 2018Article
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3 authors.
Funding
Abstract
Transactive response DNA-binding protein 43 (TDP-43) mislocalization and aggregation are hallmark features of amyotrophic lateral sclerosis and frontotemporal dementia (FTD). We have previously shown in mice that inducible overexpression of a cytoplasmically localized form of TDP-43 (TDP-43-ΔNLS) in forebrain neurons evokes neuropathological changes that recapitulate several features of TDP-43 proteinopathies. Detailed behavioral phenotyping could provide further validation for its usage as a model for FTD. In the present study, we performed a battery of behavioral tests to evaluate motor, cognitive, and social phenotypes in this model. We found that transgene (Tg) induction by doxycycline removal at weaning led to motor abnormalities including hyperlocomotion in the open field test, impaired coordination and balance in the rotarod test, and increased spasticity as shown by a clasping phenotype. Cognitive assessment demonstrated impaired recognition and spatial memory, measured by novel object recognition and Y-maze tests. Remarkably, TDP-43-ΔNLS mice displayed deficits in social behavior, mimicking a key aspect of FTD. To determine whether these symptoms were reversible, we suppressed Tg expression for 14 d in 1.5-month-old mice showing an established behavioral phenotype but modest neurodegeneration and found that motor and cognitive deficits were ameliorated; however, social performance remained altered. When Tg expression was suppressed in 6.5-month-old mice showing overt neurodegeneration, motor deficits were irreversible. These results indicate that TDP-43-ΔNLS mice display several core behavioral features of FTD with motor neuron disease, possibly due to functional changes in surviving neurons, and might serve as a valuable tool to unveil the underlying mechanisms of this and other TDP-43 proteinopathies.
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