ArticleActa neuropathologica communications2020
Deregulated expression of a longevity gene, Klotho, in the C9orf72 deletion mice with impaired synaptic plasticity and adult hippocampal neurogenesis.
Article in Acta neuropathologica communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 23 citations in OpenAlex.
- Gene deletion of Klotho in the dentate gyrus does not affect the number of adult-born granule cells.Scientific reports · 2026Article
- Klotho Function in Neurogenesis and Oligodendrogenesis: A Mini-Review Update.Journal of molecular neuroscience : MN · 2026Review
- Alpha-Ketoglutarate Ameliorates Synaptic Plasticity Deficits in APP/PS1 Mice Model of Alzheimer's Disease.Aging cell · 2025Article
- Review
- Association between Klotho levels in cerebrospinal fluid and choroid plexus enlargement in neurodegeneration.Frontiers in aging neuroscience · 2025Article
- Roadmap for C9ORF72 in Frontotemporal Dementia and Amyotrophic Lateral Sclerosis: Report on the C9ORF72 FTD/ALS Summit.Neurology and therapy · 2023Article
- Synaptic Dysfunction and Plasticity in Amyotrophic Lateral Sclerosis.International journal of molecular sciences · 2023Review
- RNA methylation influences TDP43 binding and disease pathogenesis in models of amyotrophic lateral sclerosis and frontotemporal dementia.Molecular cell · 2023Article
- Klotho Regulated by Estrogen Plays a Key Role in Sex Differences in Stress Resilience in Rats.International journal of molecular sciences · 2023Article
- Baseline Predictors of Response to Repetitive Task Practice in Chronic Stroke.Neurorehabilitation and neural repair · 2022Article
- Estrogen Enhances Dendrite Spine Function and Recovers Deficits in Neuroplasticity in the prpTDP-43Molecular neurobiology · 2022Article
- Structural Plasticity of the Hippocampus in Neurodegenerative Diseases.International journal of molecular sciences · 2022Review
- The progress inSmall GTPases · 2022Review
- Breakdown of the central synapses in C9orf72-linked ALS/FTD.Frontiers in molecular neuroscience · 2022Review
- Altered network properties in C9ORF72 repeat expansion cortical neurons are due to synaptic dysfunction.Molecular neurodegeneration · 2021Article
- Glial Cell Dysfunction inCells · 2021Review
- Synaptopathy Mechanisms in ALS Caused by C9orf72 Repeat Expansion.Frontiers in cellular neuroscience · 2021Article
- Emerging Mechanisms Underpinning Neurophysiological Impairments inFrontiers in cellular neuroscience · 2021Review
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hexanucleotide repeat expansion of C9ORF72 is the most common genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia. Synergies between loss of C9ORF72 functions and gain of toxicities from the repeat expansions contribute to C9ORF72-mediated pathogenesis. However, how loss of C9orf72 impacts neuronal and synaptic functions remains undetermined. Here, we showed that long-term potentiation at the dentate granule cells and long-term depression at the Schaffer collateral/commissural synapses at the area CA1 were reduced in the hippocampus of C9orf72 knockout mice. Using unbiased transcriptomic analysis, we identified that Klotho, a longevity gene, was selectively dysregulated in an age-dependent manner. Specifically, Klotho protein expression in the hippocampus of C9orf72 knockout mice was incorrectly enriched in the dendritic regions of CA1 with concomitant reduction in granule cell layer of dentate gyrus at 3-month of age followed by an accelerating decline during aging. Furthermore, adult hippocampal neurogenesis was reduced in C9orf72 knockout mice. Taken together, our data suggest that C9ORF72 is required for synaptic plasticity and adult neurogenesis in the hippocampus and Klotho deregulations may be part of C9ORF72-mediated toxicity.
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