TAAR1 Modulates Neuronal and Glial Density in the Neocortex Following Spinal Cord Injury

Spinal cord injury (SCI) triggers a complex cascade of secondary processes, including chronic neuroinflammation and neuroplastic remodeling both at the lesion site and in remote regions, such as the cerebral cortex. This study explores the role of trace amine-associated receptor 1 (TAAR1) in modulating neuroinflammatory responses in the somatosensory cortex following lateral spinal cord hemisection in wild-type and TAAR1-knockout (TAAR1-KO) mice. While sensorimotor recovery was comparable between genotypes, suggesting a limited impact of TAAR1 on functional recovery, TAAR1 deficiency significantly altered glial reactivity. Specifically, TAAR1-KO mice exhibited a marked increase in GFAP+ astrocyte density within the granular and pyramidal cortical layers, indicating enhanced astrogliosis. At the same time, the number of pro-inflammatory S100β+ astrocytes remained unchanged, which emphasizes the selective effect of TAAR1 on distinct astrocyte subpopulations. Additionally, TAAR1-KO mice showed a reduction in the density of Iba-1+ microglial cells. Furthermore, a decline in pyramidal neuron counts was noted, potentially indicative of impaired survival. Crucially, these differences emerged only post-injury, as genotypes were indistinguishable under baseline conditions. The obtained data demonstrate the key role of TAAR1 in modulating the glial response and expand our understanding of the molecular mechanisms of neuroinflammation in SCI, opening new avenues for the development of TAAR1-targeted neuroprotective strategies.