In Vivo Assessment of Cortical Astrocyte Network Dysfunction During Autoimmune Demyelination: Correlation With...

Area of Science:

• Neuroscience
• Immunology
• Cellular Biology

Background:

• Cortical dysfunction in multiple sclerosis (MS) is linked to physical and cognitive impairments.
• Astrocytes play a role in MS pathogenesis, with abnormal calcium signaling implicated in cortical dysfunction.
• Limited in vivo evidence exists for astrocyte calcium dysregulation in cortical MS.

Purpose of the Study:

• To investigate in vivo astrocyte calcium signaling in the somatosensory cortex during experimental autoimmune encephalomyelitis (EAE).
• To correlate astrocyte network activity with neurological deficits in a mouse model of MS.

Main Methods:

• Longitudinal analysis of spontaneous and sensory-evoked astrocyte network activity using fiber photometry.
• Utilized the experimental autoimmune encephalomyelitis (EAE) mouse model to mimic MS.

Main Results:

• EAE mice displayed spontaneous astrocyte calcium signals with increased duration and reduced amplitude.
• Cortical astrocytes in EAE mice showed decreased amplitude in response to sensory stimulation.
• Aberrant astrocyte calcium signals correlated with the onset and severity of neurological deficits.

Conclusions:

• Astrocyte network activity is imbalanced in the brain cortex during autoimmune inflammation in MS.
• Astrocyte pathobiology is a relevant mechanism underlying cortical dysfunction in MS.
• Targeting astrocyte calcium signaling may offer therapeutic potential for MS-related cortical dysfunction.