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GFAP mRNA fluctuates in synchrony with chronic relapsing EAE symptoms in SJL/J mice
A Kothavale1, D Di Gregorio, F P Somera
1Department of Neurology, VA Medical Center, Palo Alto 94304, USA.
Abstract:
Activation of astrocytes and hypertrophy of their processes is a result 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 axons. Experimental allergic encephalomyelitis (EAE), a laboratory model for MS, is also accompanied by astrocytic hyperactivity. We have previously shown the formation of plaque-like structures which stain heavily for glial fibrillary acidic protein (GFAP) in the brains and spinal cords of SJL/J mice after several episodes of chronic relapsing EAE (Smith and Eng: J Neurosci Res 18:203, 1987). To further investigate the mechanisms of this phenomenon, we have measured the levels of mRNA for GFAP throughout the course of three episodes and recoveries of EAE in the SJL/J mouse. Mice were immunized with spinal cord homogenate and subsequently developed EAE. After recovery they were again immunized at appropriate intervals, resulting in successive episodes of EAE, with partial or complete recovery between the paralytic stages. At appropriate times in the course of the different stages of EAE, spinal cords were dissected and RNA was prepared from each spinal cord. RNA was analyzed 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 mild symptoms increased to sixfold the control level (P < 0.02) and to 20-fold in those with paralysis (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
Astrocytic gliosis, a hallmark of multiple sclerosis (MS), involves increased glial fibrillary acidic protein (GFAP) mRNA in experimental allergic encephalomyelitis (EAE) mouse models. This study quantifies GFAP mRNA during EAE relapses, revealing significant elevations.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Astrocytic activation and hypertrophy are common in central nervous system pathologies.
- Astrocytic gliosis, marked by glial fibrillary acidic protein (GFAP), is prominent in multiple sclerosis (MS).
- Experimental allergic encephalomyelitis (EAE) serves as an animal model for MS, exhibiting astrocytic hyperactivity.
Purpose of the Study:
- To investigate the mechanisms of astrocytic gliosis in a chronic relapsing EAE model.
- To measure glial fibrillary acidic protein (GFAP) mRNA levels during multiple episodes and recoveries of EAE in SJL/J mice.
Main Methods:
- Induction of three successive episodes of EAE in SJL/J mice with recovery periods.
- Dissection of spinal cords at various stages of EAE for RNA extraction.
- Northern blot analysis to quantify messenger RNA (mRNA) levels for GFAP and neurofilament-light (NF-L) as a control.
Main Results:
- GFAP mRNA levels increased significantly with the onset of the first EAE episode.
- A sixfold increase in GFAP mRNA was observed in mice with mild symptoms (P < 0.02).
- A 20-fold increase in GFAP mRNA was detected in mice with paralysis (P < 0.01).
Conclusions:
- GFAP mRNA levels dynamically change during the course of EAE.
- The study provides quantitative data on GFAP mRNA upregulation in response to EAE.
- Findings contribute to understanding the molecular mechanisms of astrogliosis in MS models.