# The Spatiotemporal Expression of SOCS3 in the Brainstem and Spinal Cord of Amyotrophic Lateral Sclerosis Mice

## TL;DR

This study shows that SOCS3 levels increase in the brainstem and spinal cord of ALS mice, linking it to inflammation and neuronal loss.

## Contribution

This is the first study to show SOCS3 upregulation in ALS progression and its association with astrogliosis and neuronal loss.

## Key findings

- SOCS3 protein levels are significantly increased in the brainstem of SOD1-G93A ALS mice.
- SOCS3 levels in spinal cords of ALS mice are upregulated at pre-symptomatic and early symptomatic stages.
- SOCS3 upregulation correlates with increased astrocyte and microglia/macrophage activity and neuronal loss.

## Abstract

Amyotrophic lateral sclerosis (ALS) is characterized by the progressive loss of motor neurons from the brain and spinal cord. The excessive neuroinflammation is thought to be a common determinant of ALS. Suppressor of cytokine signaling-3 (SOCS3) is pathologically upregulated after injury/diseases to negatively regulate a broad range of cytokines/chemokines that mediate inflammation; however, the role that SOCS3 plays in ALS pathogenesis has not been explored. Here, we found that SOCS3 protein levels were significantly increased in the brainstem of the superoxide dismutase 1 (SOD1)-G93A ALS mice, which is negatively related to a progressive decline in motor function from the pre-symptomatic to the early symptomatic stage. Moreover, SOCS3 levels in both cervical and lumbar spinal cords of ALS mice were also significantly upregulated at the pre-symptomatic stage and became exacerbated at the early symptomatic stage. Concomitantly, astrocytes and microglia/macrophages were progressively increased and reactivated over time. In contrast, neurons were simultaneously lost in the brainstem and spinal cord examined over the course of disease progression. Collectively, SOCS3 was first found to be upregulated during ALS progression to directly relate to both increased astrogliosis and increased neuronal loss, indicating that SOCS3 could be explored to be as a potential therapeutic target of ALS.