Proteomic profiling of the epileptic dentate gyrus.
The development of epilepsy is often associated with marked changes in central nervous system cell structure and function. Along these lines, reactive gliosis and granule cell axonal sprouting within the dentate gyrus of the hippocampus are commonly observed in individuals with temporal lobe epilepsy (TLE). Here we used the pilocarpine model of TLE in mice to screen the proteome and phosphoproteome of the dentate gyrus to identify molecular events that are altered as part of the pathogenic process. Using a two-dimensional gel electrophoresis-based approach, followed by liquid chromatography-tandem mass spectrometry, 24 differentially expressed proteins, including 9 phosphoproteins, were identified. Functionally, these proteins were organized into several classes, including synaptic physiology, cell structure, cell stress, metabolism and energetics. The altered expression of three proteins involved in synaptic physiology, actin, profilin 1 and α-synuclein was validated by secondary methods. Interestingly, marked changes in protein expression were detected in the supragranular cell region, an area where robust mossy fibers sprouting occurs. Together, these data provide new molecular insights into the altered protein profile of the epileptogenic dentate gyrus and point to potential pathophysiologic mechanisms underlying epileptogenesis.
Li
Aiqing
A
Key Lab. for Organ Failure Research, Education Ministry of P.R. China, Southern Medical University, Guangzhou, China.
Choi
Yun-Sik
YS
Dziema
Heather
H
Cao
Ruifeng
R
Cho
Hee-Yeon
HY
Jung
Yeon Joo
YJ
Obrietan
Karl
K
D000199:Actins / Q000378:metabolism; D000818:Animals; D018891:Dentate Gyrus / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D004569:Electroencephalography / Q000379:methods; D015180:Electrophoresis, Gel, Two-Dimensional / Q000379:methods; D004827:Epilepsy / Q000139:chemically induced / Q000473:pathology*; D005452:Fluoresceins; D008297:Male; D051379:Mice; D009474:Neurons / Q000187:drug effects; D009930:Organic Chemicals; D010750:Phosphoproteins / Q000378:metabolism; D010862:Pilocarpine; D020543:Proteome / Q000378:metabolism*; D040901:Proteomics / Q000379:methods*; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry / Q000379:methods; D013997:Time Factors
D000199:Actins; D005452:Fluoresceins; D009930:Organic Chemicals; D010750:Phosphoproteins; D020543:Proteome; C435731:fluoro jade; D010862:Pilocarpine