Study on peripheral non-specific stimulated T lymphocytesin the cuprizone model: An alternative perspective

Melike Çakan Ercan, Study on Peripheral Non-specific Stimulated T Lymphocytes in the Cuprizone Model: An Alternative Perspective. Multiple sclerosis (MS) is a chronic demyelinating disease of the CNS, involving neuroinflammation and neurodegeneration. The initiating factor remains unclear. Various experimental animal models address aspects of MS, but none fully elucidate its pathophysiology. Our study investigates the role of non-specifically activated peripheral T lymphocytes in CNS demyelination using a stepwise experimental model.Biodistribution studies in healthy mice showed that activated T lymphocytes migrate to the CNS more efficiently than naive T lymphocytes, regardless of the lymphoid origin. In mice with cuprizone-induced toxic demyelination, both naive and activated T lymphocytes exhibited increased CNS migration, likely due to neurodegeneration and local inflammation.Activation enhanced organ-specific migration, notably affecting the CNS. In the toxic demyelination group, adding T lymphocyte injection to cuprizone-induced demyelination created a double induction model. Despite this, experimental autoimmune encephalomyelitis (EAE) scores did not significantly increase.Behavioral experiments revealed worsened locomotion, allodynia, and increased anxiety symptoms in both double induction and cuprizone-only groups compared to controls. Histopathological studies found that cuprizone alone caused widespread demyelination and increased microglia activation and numbers, which were more pronounced with T lymphocyte injection. Our study shows that non-specifically stimulated peripheral T lymphocytes contribute to CNS demyelination at both histopathological and clinical levels. The model, highlighting local inflammation and neurodegeneration, may offer an alternative to progressive MS models.