Acute Colon Inflammation Triggers Primary Motor Cortex Glial Activation, Neuroinflammation, Neuronal Hyperexcitability, and Motor Coordination Deficits

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2022-05Department
Biomedicina, Biotecnología y Salud PúblicaSource
International Journal of Molecular Sciences, Vol. 23, Núm. 10Abstract
Neuroinflammation underlies neurodegenerative diseases. Herein, we test whether acute
colon inflammation activates microglia and astrocytes, induces neuroinflammation, disturbs neuron
intrinsic electrical properties in the primary motor cortex, and alters motor behaviors. We used a rat
model of acute colon inflammation induced by dextran sulfate sodium. Inflammatory mediators and
microglial activation were assessed in the primary motor cortex by PCR and immunofluorescence
assays. Electrophysiological properties of the motor cortex neurons were determined by whole-cell
patch-clamp recordings. Motor behaviors were examined using open-field and rotarod tests. We
show that the primary motor cortex of rats with acute colon inflammation exhibited microglial and
astrocyte activation and increased mRNA abundance of interleukin-6, tumor necrosis factor-alpha,
and both inducible and neuronal nitric oxide synthases. These changes were accompanied by a
reduction in resting membrane potential and rheobase and increased input resistance and action
potential frequency, indicating motor neuron hyperexcitability. In addition, locomotion and motor
coordination were impaired. In conclusion, acute colon inflammation induces motor cortex microglial
and astrocyte activation and inflammation, which led to neurons’ hyperexcitability and reduced motor
coordination performance. The described disturbances resembled some of the early features found in
amyotrophic lateral sclerosis patients and animal models, suggesting that colon inflammation might
be a risk factor for developing this disease
Subjects
colon inflammation; motor neurons; microglial and astrocyte activation; neuroinflammation; neurodegeneration; hyperexcitability; motor coordinationCollections
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