Taar1 modulates neuronal and glial density in the neocortex following spinal cord injury

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Abstract

Spinal cord injury (SCI) initiates a complex cascade of secondary pathological processes, including chronic neuroinflammation and neuroplastic remodeling both at the lesion site and in distant 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 mice and TAAR1-knockout (TAAR1-KO). Behavioral tests revealed no significant differences in sensorimotor recovery, suggesting a limited impact of TAAR1 on functional recovery. However, immunohistochemical analysis uncovered substantial alterations in 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.

About the authors

D. S. Kalinina

Sirius University of Science and Technology; St. Petersburg State University, Institute of Translational Biomedicine; Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences

Email: kalinina.ds@talantiuspeh.ru
Sirius Federal Territory, Russia; St. Petersburg, Russia; St. Petersburg, Russia

A. A. Chesnokov

Sirius University of Science and Technology

Sirius Federal Territory, Russia

E. A. Romanyuk

Sirius University of Science and Technology

Sirius Federal Territory, Russia

A. D. Buglinina

Sirius University of Science and Technology

Sirius Federal Territory, Russia

D. V. Khuzin

Sirius University of Science and Technology

Sirius Federal Territory, Russia

S. I. Milov

Sirius University of Science and Technology

Sirius Federal Territory, Russia

S. P. Konavalova

Sirius University of Science and Technology

Sirius Federal Territory, Russia

P. Yu. Shkorbatova

St. Petersburg State University, Institute of Translational Biomedicine; Pavlov Institute of Physiology, Russian Academy of Sciences

St. Petersburg, Russia; St. Petersburg, Russia

N. V. Pavlova

Pavlov Institute of Physiology, Russian Academy of Sciences

St. Petersburg, Russia

A. D. Belskaya

St. Petersburg State University, Institute of Translational Biomedicine

St. Petersburg, Russia

R. R. Gainetdinov

St. Petersburg State University, Institute of Translational Biomedicine

St. Petersburg, Russia

P. E. Musienko

Pavlov Institute of Physiology, Russian Academy of Sciences; Life Improvement by Future Technologies (LIFT) Center; Federal Center for Brain and Neurotechnologies

Email: pol-spb@mail.ru
St. Petersburg, Russia; Moscow, Russia; Moscow, Russia

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