Expression of insulin‐like growth factor‐II and leukemia inhibitory factor antibody immunostaining on the ionized calcium‐binding adaptor molecule 1‐positive microglias in the spinal cord of amyotrophic lateral sclerosis patients

Abstract

Amyotrophic lateral sclerosis (ALS) is a progressive degenerative disease involving the upper and lower motor neuron systems. Activated microglia are reported to enhance motor neuron death by secreting neurotoxic cytokines in SOD1-transgenic mice. Recent studies have provided evidence that chronic stimulation leads microglia to acquire an anti-inflammatory phenotype, characterized by activated morphology and induction of neuroprotective and immunoregulatory molecules. However, little information is available on the protective functions of microglia in the ALS spinal cord. To investigate the roles of microglia in ALS, we examined the appearance of ionized calcium-binding adaptor molecule 1-positive (Iba1-positive) microglia as correlated to the disease duration and immunohistochemical expression of neurogrowth factors in the ALS spinal cord. In this study, the number of Ibal-positive rod-like microglia significantly increased in the ALS spinal cord compared to controls. The number of ramified microglia was positively correlated with the number of normal-looking neurons and clinical duration of ALS patients; however, the number of rod-like microglia was not correlated with that of abnormal neurons, nor with the clinical duration of the disease. Some rod-like microglia were positive for anti-insulin-like growth factor-II (IGF II) and anti-leukemia inhibitory factor (LIF) immunostaining. Motor neurons in the ALS spinal cords also showed immunore-activity for IGF-II, LIF and the receptors of IGF-II and LIE Taken together, these findings suggest that at least some microglia might have a protective effect on motor neurons in the ALS spinal cord. Neuroprotective and/or neurotoxic effects of microglia on motor neurons should be further studied.