ArticleBrain and behavior2013
Early presymptomatic cholinergic dysfunction in a murine model of amyotrophic lateral sclerosis.
Article in Brain and behavior, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 40 papers, 1 of them a synthesis that pooled it.
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Who cites it
40 citing papers in PubMed, 1 synthesis or guideline pooled it, 73 citations in OpenAlex.
- Selection and Prioritization of Candidate Drug Targets for Amyotrophic Lateral Sclerosis Through a Meta-Analysis Approach.Journal of molecular neuroscience : MN · 2017Pooled it
- How do we get from hyperexcitability to excitotoxicity in amyotrophic lateral sclerosis?Brain : a journal of neurology · 2024Review
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- Potential contribution of spinal interneurons to the etiopathogenesis of amyotrophic lateral sclerosis.Frontiers in neuroscience · 2024Review
- Article
- Inhibitory interneurons show early dysfunction in a SOD1 mouse model of amyotrophic lateral sclerosis.The Journal of physiology · 2023Article
- Chaperone-Dependent Mechanisms as a Pharmacological Target for Neuroprotection.International journal of molecular sciences · 2023Review
- Sensory Involvement in Amyotrophic Lateral Sclerosis.International journal of molecular sciences · 2022Review
- Accumulation of misfolded SOD1 outlines distinct patterns of motor neuron pathology and death during disease progression in a SOD1Brain pathology (Zurich, Switzerland) · 2022Article
- Maintenance of neurotransmitter identity by Hox proteins through a homeostatic mechanism.Nature communications · 2022Article
- cGAS and DDX41-STING mediated intrinsic immunity spreads intercellularly to promote neuroinflammation in SOD1 ALS model.iScience · 2022Article
- Caudal-Rostral Progression of Alpha Motoneuron Degeneration in the SOD1Antioxidants (Basel, Switzerland) · 2022Article
- Neuromuscular Junction Dysfunction in Amyotrophic Lateral Sclerosis.Molecular neurobiology · 2022Review
- Sigma-1 Receptor Is Critical for Mitochondrial Activity and Unfolded Protein Response in Larval Zebrafish.International journal of molecular sciences · 2021Article
- Acetylcholine and spinal locomotor networks: The insider.Physiological reports · 2021Review
- ALS-CSF-induced structural changes in spinal motor neurons of rat pups cause deficits in motor behaviour.Experimental brain research · 2021Article
- How Degeneration of Cells Surrounding Motoneurons Contributes to Amyotrophic Lateral Sclerosis.Cells · 2020Review
- A role for SUMOylation in the Formation and Cellular Localization of TDP-43 Aggregates in Amyotrophic Lateral Sclerosis.Molecular neurobiology · 2020Article
- Exciting Complexity: The Role of Motor Circuit Elements in ALS Pathophysiology.Frontiers in neuroscience · 2020Review
- Developmental Expression of Mutant PFN1 in Motor Neurons Impacts Neuronal Growth and Motor Performance of Young and Adult Mice.Frontiers in molecular neuroscience · 2019Article
Corrections and comments
- Erratum issued
Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sporadic and familiar amyotrophic lateral sclerosis (ALS) cases presented lower cholinergic activity than in healthy individuals in their still preserved spinal motoneurons (MNs) suggesting that cholinergic reduction might occur before MN death. To unravel how and when cholinergic function is compromised, we have analyzed the spatiotemporal expression of choline acetyltransferase (ChAT) from early presymptomatic stages of the SOD1(G93A) ALS mouse model by confocal immunohistochemistry. The analysis showed an early reduction in ChAT content in soma and presynaptic boutons apposed onto MNs (to 76%) as well as in cholinergic interneurons in the lumbar spinal cord of the 30-day-old SOD1(G93A) mice. Cholinergic synaptic stripping occurred simultaneously to the presence of abundant surrounding major histocompatibility complex II (MHC-II)-positive microglia and the accumulation of nuclear Tdp-43 and the appearance of mild oxidative stress within MNs. Besides, there was a loss of neuronal MHC-I expression, which is necessary for balanced synaptic stripping after axotomy. These events occurred before the selective raise of markers of denervation such as ATF3. By the same time, alterations in postsynaptic cholinergic-related structures were also revealed with a loss of the presence of sigma-1 receptor, a Ca2+ buffering chaperone in the postsynaptic cisternae. By 2 months of age, ChAT seemed to accumulate in the soma of MNs, and thus efferences toward Renshaw interneurons were drastically diminished. In conclusion, cholinergic dysfunction in the local circuitry of the spinal cord may be one of the earliest events in ALS etiopathogenesis.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.