Abstract
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease, the accurate pathogenesis of ALS hasn’t been found up to now. The previous studied results revealed that the abnormal alterations of some non-motor neurons (MN) were one of potential pathogenesis of MN death in ALS. Therefore, we studied the altered features of 5-hydroxytryptamine (5-HT) distribution and expression in the spinal cord and brainstem of both Tg(SOD1*G93A)1Gur (TG) and wild-type (WT) mice through the fluorescent immunohistochemistry and Western blot methods using the biomarkers of 5-HT neuron and synapse (both 5-HT and Tryptophan hydroxylase 2). Our results revealed that 5-HT synapses mainly distributed in the funiculus lateralis, the anterior horn, the posterior horn, the central lateral column and the around central canal in the cervical, thoracic and lumbar segments of spinal cord, as well as both the raphe nucleus and the lateral paragigantocellular nucleus of brainstem, and gradually reduced following by the age increase in WT mice. However, both 5-HT synapses and 5-hydroxytryptamine receptor 1A (5-HTR1A), but not 5-HTR2A, in spinal cord and 5-HT neurons in brainstem gradually increased following by the progression of disease and presented the significantly negative correlation between the increased distribution of both 5-HT synapses and neurons and neural cell death at the onset and/or progression stages of TG mice. Therefore, it is speculated that the distribution changes of 5-HT synapses in spinal cord and 5-HT neurons in brainstem are closely associated with neuron death, is a potential pathogenesis of ALS.