GFAP MESSENGER-RNA FLUCTUATES IN SYNCHRONY WITH CHRONIC RELAPSING EAESYMPTOMS IN SJL J MICE/

Activation of astrocytes and hypertrophy of their processes is a resul t of a number of pathological conditions in the central nervous system . Astrocytic gliosis is especially prominent in multiple sclerosis (MS ), where astrocytic fibers form a dense matrix around demyelinated axo ns. Experimental allergic encephalomyelitis (EAE), a laboratory model for MS, is also accompanied by astrocytic hyperactivity. We have previ ously shown the formation of plaque-like structures which stain heavil y for glial fibrillary acidic protein (GFAP) in the brains and spinal cords of SJL/J mice aft er several episodes of chronic relapsing EAE ( Smith and Eng: J Neurosci Res 18:203, 1987). To further investigate th e mechanisms of this phenomenon, we have measured the levels of mRNA f or GFAP throughout the course of three episodes and recoveries of EAE in the SJL/J mouse. Mice were immunized with spinal cord homogenate an d subsequently developed EAE. After recovery they were again immunized at appropriate intervals, resulting in successive episodes of EAE, wi th partial or complete recovery between the paralytic stages. At appro priate times in the course of the different stages of EAE, spinal cord s were dissected and RNA was prepared from each spinal cord. RNA was a nalyzed by Northern blots to determine the levels of mRNA for GFAP and , as a control, for the 70 kDa neurofilament (NF-L). With the onset of the first EAE episode GFAP mRNA in spinal cords from animals with mil d symptoms increased to sixfold the control level (P < 0.02) and to 20 -fold in those with paralysis (P < 0.01), With recovery, the GFAP mRNA level decreased to twice the control. With each subsequent episode GF AP mRNA levels again rose, then subsided with recovery. After several episodes, a chronic but stable neurological deficit was established, w ith GFAP mRNA at about eightfold the control levels (P < 0.01). Over t he course of several episodes, the GFAP rose to about 2.8 times the co ntrol, while vimentin increased by a factor of 3.6. Thus multiple epis odes of EAE resulted in upregulation of GFAP mRNA and accumulation of GFAP, which are associated with astrocyte activation and hypertrophy. Similar events may occur in the human demyelinative disease MS, where multiple episodes of inflammatory cell invasion occur, resulting in a neurological deficit. (C) 1995 Wiley-Liss, Inc.