Long-Term 5-HT_1A Receptor Agonist NLX-112 Treatment Improves Functional Recovery After Spinal Cord Injury

Area of Science:

• Neuroscience
• Pharmacology
• Regenerative Medicine

Background:

• Spinal cord injury (SCI) causes motor and autonomic deficits due to damage in descending serotonergic pathways.
• SCI leads to reduced serotonin signaling and increased spinal 5-HT1A receptors.
• Previous studies showed brief NLX-112 administration improved lower urinary tract (LUT) function post-SCI.

Purpose of the Study:

• To evaluate the long-term efficacy of NLX-112, a 5-HT1A receptor agonist, in a rat model of thoracic 8 (T8) contusive SCI.
• To assess the impact of chronic NLX-112 treatment on locomotion, LUT function, bladder morphology, and spinal 5-HT1A receptor expression.

Main Methods:

• Rats with T8 contusive SCI received long-term NLX-112 treatment starting two weeks post-injury for six weeks.
• Evaluated outcomes included locomotion, LUT function, bladder weight, bladder wall thickness, and spinal 5-HT1A receptor density in L4 and L6/S1 segments.

Main Results:

• NLX-112 treatment dose-dependently improved locomotion and LUT function in SCI rats.
• Treatment reduced bladder weight and wall thickness compared to vehicle controls.
• NLX-112 decreased the SCI-induced upregulation of spinal 5-HT1A receptors.

Conclusions:

• Long-term activation of serotonin 5-HT1A receptors with NLX-112 demonstrates significant therapeutic potential for SCI.
• NLX-112 may offer a promising treatment strategy for improving motor and autonomic functions after spinal cord injury.