Chronic gliosis induced by loss of S-100B: knockout mice have enhanced GFAP-immunoreactivity but blunted response to a serotonin challenge.
Serotonin (5-HT) can induce a release of intraglial S-100B and produce a change in glial morphology. Because S-100B can inhibit polymerization of glial fibrillary acidic protein (GFAP), we hypothesize that glial reactivity may reflect the loss of intraglial S-100B. Adult male transgenic S-100B homozygous knockout (-/-) mice (KO) and wild-type CD-1 (WT) mice were studied. S-100B-immunoreactivity (IR) was seen in the brain tissue of WT (CD-1) but not S-100B KO (-/-) mice. GFAP-IR was seen in both WT (CD-1) and S-100B KO (-/-) glia cells, but S-100B KO (-/-) GFAP-IR cells appeared larger, darker, and more branched than in WT (CD-1). To compare the response of GFAP-IR cells to 5-HT in S-100B KO (-/-) and WT (CD-1) mice, we injected animals with para-chloroamphetamine (PCA) over 2 days (5 and 10 mg/ml). PCA is a potent 5-HT releaser which can induce gliosis in the rodent brain. In WT (CD-1) mice, the size, branching, and density of GFAP-IR cells were significantly increased after PCA injections. No increase in GFAP-IR activation was seen in the S-100B KO (-/-) after PCA injections. Cell-specific densitometry (set at a threshold of 0-150 based on a scale of 255) in these animals statistically showed an increase in GFAP-IR after PCA injections in WT (CD-1) but not S-100B KO (-/-) mice. These results are consistent with the hypothesis that 5-HT may modulate glial morphology by inducing a release of intracellular S-100B, and this pathway is inoperable in the S-100B KO (-/-).
Chang
Matthew S
MS
Department of Biology, New York University, 10-09 Silver Building; 100 Washington Square East, New York, NY 10003 USA.
Ariah
Lisa M
LM
Marks
Alexander
A
Azmitia
Efrain C
EC
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002908:Chronic Disease; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism*; D005911:Gliosis / Q000378:metabolism* / Q000473:pathology*; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D051379:Mice; D018345:Mice, Knockout; D009414:Nerve Growth Factors; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000235:genetics*; D012701:Serotonin / Q000494:pharmacology*
D005904:Glial Fibrillary Acidic Protein; D009414:Nerve Growth Factors; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; D012701:Serotonin