Aging alters mechanisms underlying voluntary movements in spinal motor neurons of mice, primates and humans.
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ABSTRACT:
PROVIDER: PRJNA941252 | ENA |
REPOSITORIES: ENA
Dataset's files
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| SRR23707225_1.fastq.gz | Fastqsanger.gz | |||
| SRR23707225_2.fastq.gz | Fastqsanger.gz | |||
| SRR23707226_1.fastq.gz | Fastqsanger.gz | |||
| SRR23707226_2.fastq.gz | Fastqsanger.gz | |||
| SRR23707227_1.fastq.gz | Fastqsanger.gz |
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Project description:Spinal motor neurons have been implicated in the loss of motor function that occurs with advancing age. However, the cellular and molecular mechanisms that impair the function of these neurons during aging remain unknown. Here, we show that motor neurons do not die in old female and male mice, rhesus monkeys, and humans. Instead, these neurons selectively shed excitatory synaptic inputs throughout the soma and dendritic arbor during aging. By examining the translatome , we also show that aging alters the molecular composition of motor neurons in both male and female mice. Aging motor neurons present with changes in genes and molecular pathways with roles in glia-mediated synaptic pruning, and inflammation. They also exhibit changes in pathways with roles in axonal regeneration caused by axotomy and Amyotrophic Lateral Sclerosis (ALS). Thus, we have identified cellular and molecular mechanisms altered in aged motor neurons that could serve as therapeutic targets to preserve motor function during aging.
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Project description:Spinal motor neurons have been implicated in the loss of motor function that occurs with advancing age. However, the cellular and molecular mechanisms that impair the function of these neurons during aging remain unknown. Here, we show that motor neurons do not die in old female and male mice, rhesus monkeys, and humans. Instead, these neurons selectively and progressively shed excitatory synaptic inputs throughout the soma and dendritic arbor during aging. Thus, aged motor neurons contain a motor circuitry with a reduced ratio of excitatory to inhibitory synapses that may be responsible for the diminished ability to activate motor neurons to commence movements. An examination of the motor neuron translatome (ribosomal transcripts) in male and female mice reveals genes and molecular pathways with roles in glia-mediated synaptic pruning, inflammation, axonal regeneration, and oxidative stress that are upregulated in aged motor neurons. Some of these genes and pathways are also found altered in motor neurons affected with amyotrophic lateral sclerosis (ALS) and responding to axotomy, demonstrating that aged motor neurons are under significant stress. Our findings show mechanisms altered in aged motor neurons that could serve as therapeutic targets to preserve motor function during aging.
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