Background - Neuroinflammation and glial cell dysfunction are associated with neurodegenerative diseases and are central to disease pathology. Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease associated with a specific loss of motor neurons (MNs) leading to motor dysfunctions. The SOD1^G93A mouse model of ALS is accompanied by increased levels of neuroinflammation, reactive astrocytes and an impaired ability of astrocytes to maintain K⁺ homeostasis. This study aims to evaluate the therapeutic effect of phytosomal curcumin, a cytokine suppressive anti-inflammatory drug in ameliorating ALS disease progression and motor symptoms in SOD1^G93A mice.

Methods – In this study, we used various behavioural tests, extracellular electrophysiological recordings and imaging techniques to assess motor functions, dysregulation of K⁺ ion homeostasis, and neuroinflammation levels.

Key findings – Through extracellular electrophysiological recordings, we observed a significant reduction in the astrocytic K⁺ clearance rate in layer 2/3 of the primary motor cortex of aged SOD1^G93A mice fed with a normal diet. This decrease was accompanied by astrocytic hypertrophy and increased reactivity. Additionally, our preliminary behavioural results indicate significant motor deficits in SOD1^G93A mice that were fed with a normal diet in the open field test and the accelerod test, while a curcumin-enriched diet had a modest impact on SOD1^G93A mice motor functions.

Conclusions – Our preliminary findings indicate that curcumin had a limited effect on rescuing motor deficits in SOD1^G93A mice. However, the ability of curcumin to reduce neuroinflammation and restore K⁺ homeostasis in SOD1^G93A mice is still under investigation.