Conditional Astrocyte Rac1KO Attenuates Hyperreflexia after Spinal Cord Injury.

Area of Science:

• Neuroscience
• Cell Biology
• Physiology

Background:

• Spasticity, a common consequence of spinal cord injury (SCI), is characterized by muscle hypertonia and hyperreflexia.
• The monosynaptic H-reflex, a measure of spinal cord excitability, loses its rate-dependent depression (RDD) in SCI, indicating hyperreflexia.
• Astrocytes, crucial components of the tripartite synapse, are increasingly recognized for their role in neuronal function and plasticity.

Purpose of the Study:

• To investigate the role of astrocytic Rac1 in the development of SCI-induced spasticity and hyperreflexia.
• To determine if selective deletion of Rac1 in astrocytes could ameliorate SCI-related spasticity.

Main Methods:

• Utilized a transgenic cre-flox system to create mice with selective Rac1 knockout (Rac1KO) in astrocytes.
• Induced mild contusion SCI in adult male and female mice.
• Assessed H-reflex RDD, dendritic spine morphology on α-motor neurons, and glutamate transporter-1 (GLT-1) expression post-SCI.

Main Results:

• SCI induced loss of H-reflex RDD (hyperreflexia) in control (Rac1^wt) animals.
• Astrocytic Rac1KO mice exhibited near-normal H-reflex RDD, indicating reduced hyperreflexia.
• SCI-induced dendritic spine dysgenesis on α-motor neurons was reduced in astrocytic Rac1KO mice, alongside increased GLT-1 expression in the ventral spinal cord.

Conclusions:

• Astrocytic Rac1 activity significantly contributes to SCI-induced hyperreflexia and spasticity.
• Targeting astrocytic Rac1 signaling offers a potential therapeutic strategy for managing spasticity post-SCI.
• Modulating astrocyte function, specifically Rac1 signaling, impacts spinal reflex excitability and neuronal plasticity after injury.