Immunohistochemical study on the distribution of glycogen synthase kinase 3α in the central nervous system of SOD1G93A transgenic mice

Objective: To identify glycogen synthase kinase (GSK) 3 alpha expression in a mouse model of familial amyotrophic lateral sclerosis (ALS), we investigated the changes of GSK3 alpha in the central nervous system of SOD1(G93A) transgenic mice by immunohistochemistry. Methods: We used 12 SOD1(G93A) transgenic and ten wild-type (wt) SOD1 transgenic mice bred by 'The Jackson Laboratory' under the strain designations B6SJL-TgN (SOD1(G93A))1 Gur/J and B6SJL-TgN (SOD1) 2 Gur/J, respectively. Immunohistochemistry was performed in accordance with the free-floating method described earlier. Results: In symptomatic transgenic mice, GSK3 alpha-immunoreactive astrocytes were detected in the spinal cord, brainstem and cerebellum of symptomatic SOD1(G93A) transgenic mice. In contrast to symptomatic mice, no GSK3 alpha-immunoreactive astrocytes were observed in any brain region of wtSOD1 and pre-symptomatic mice, and the number and intensity of stained cells were not different at the age of 8 and 13 weeks. Discussion: These results provide the first evidence that GSK3 alpha-immunoreactive astrocytes were found in the CNS of SOD1(G93A) transgenic mice after clinical symptoms, suggesting a possible role in the pathologic process of ALS. However, the mechanisms underlying the increased immunoreactivity for GSK3 alpha and the functional implications require elucidation. [Neurol Res 2008; 30: 926 -931]