In vitro differences between astrocytes of control and wobbler mice spinal cord.
The Wobbler mouse, a model of amyotrophic lateral sclerosis (ALS), presents motorneuron degeneration and pronounced astrogliosis in the spinal cord. We have studied factors controlling astrocyte proliferation in cultures derived from Wobbler and control mice spinal cord. Basal rate of [3H]thymidine incorporation was 15 times lower in Wobbler astrocytes. While in control cultured cells interleukin-1alpha (IL-1) and corticosterone (CORT) significantly increased proliferation, both agents were inactive in Wobbler astrocytes. The lack of response to CORT was not due to the absence of glucocorticoid receptors, because similar receptor amounts were found in Wobbler and control astrocytes. In contrast to IL-1 and CORT, transforming growth factor-beta1 (TGF-beta1) substantially increased proliferation of Wobbler astrocytes but not of control cells. Differences in response to TGF-beta1 were also obtained by measuring glial fibrillary acidic protein (GFAP) immunoreaction intensity, which was substantially higher in Wobbler astrocytes. Thus, abnormal responses to different mitogens characterized Wobbler astrocytes in culture. We suggest that TGF-beta1 may play a role in the reactive gliosis and GFAP hyperexpression found in the degenerating spinal cord of this model of ALS.
González Deniselle
M C
MC
Instituto de Biología y Medicina Experimental, Buenos Aires, Argentina.
Lavista-Llanos
S
S
Ferrini
M G
MG
Lima
A E
AE
Roldán
A G
AG
De Nicola
A F
AF
D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003345:Corticosterone / Q000494:pharmacology; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005911:Gliosis / Q000235:genetics / Q000473:pathology; D007375:Interleukin-1 / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008818:Mice, Neurologic Mutants; D016472:Motor Neuron Disease / Q000235:genetics / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology; D011281:Pregnatrienes / Q000494:pharmacology; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D012016:Reference Values; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D013936:Thymidine / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D005904:Glial Fibrillary Acidic Protein; D007375:Interleukin-1; D018696:Neuroprotective Agents; D011281:Pregnatrienes; D011965:Receptors, Glucocorticoid; D016212:Transforming Growth Factor beta; C074965:U 74389F; D013936:Thymidine; D003345:Corticosterone