Enhanced Fos expression in rat lumbar spinal cord cultured with cerebrospinal fluid from patients with amyotrophic lateral sclerosis

The etiology of amyotrophic lateral sclerosis (ALS) remains unknown although an existence of neurotoxic substances in cerebrospinal fluid (CSF) from ALS patients have been postulated. In order to investigate a possible effect of CSF from ALS patients on cellular signaling in spinal neurons, we compared Fos-like immunoreactivity (Fos-LI) in organotypic cultures of rat lumbar spinal cord after addition of CSF from ALS patients or another neurologic disease. Fos-LI was normally present predominantly in dorsal horn neurons, whereas only a few ventral horn neurons were positive for Fos-LI. The number of Fos-LI positive neurons significantly increased in dorsal horn with addition of CSF from ALS patients as well as glutamate at 100 μM. However, the increase was not observed with addition of CSF from other neurologic diseases. The increase in Fos-LI positive neurons in dorsal horn was reversed by a further supplement of MK801, an N-methyl-D-aspartate (NMDA) receptor antagonist, but not of CNQX, an α-amino-3-hydroxy-5-methyl-4- isoxazole propionic acid (AMPA)/kainate antagonist. These results indicate that there may be substances in CSF from ALS patients that stimulate Fos expression in certain populations of spinal neurons via the NMDA receptors.