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 althoug h an existence of neurotoxic substances in cerebrospinal fluid (CSF) from A LS patients have been postulated. In order to investigate a possible effect of CSF from ALS patients on cellular signaling in spinal neurons, we compa red Fos-like immunoreactivity (Fos-Ll) in organotypic cultures of rat lumba r 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-L1. The numb er of Fos-LI positive neurons significantly increased in dorsal horn with a ddition of CSF from ALS patients as well as glutamate at 100 mu M. However, the increase was not observed with addition of CSF from other neurologic d iseases. The increase in Fos-LI positive neurons in dorsal horn was reverse d by a further supplement of MK801, an N-methyl-D-aspartate (NMDA) receptor antagonist, but not of CNQX, an alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)/kainate antagonist. These results indicate that ther e may be substances in CSF from ALS patients that stimulate Fos expression in certain populations of spinal neurons via the NMDA receptors.