Plasticity response in the contralesional hemisphere after subtle neurotrauma: gene expression profiling after partial deafferentation of the hippocampus.
Neurotrauma or focal brain ischemia are known to trigger molecular and structural responses in the uninjured hemisphere. These responses may have implications for tissue repair processes as well as for the recovery of function. To determine whether the plasticity response in the uninjured hemisphere occurs even after a subtle trauma, we subjected mice to a partial unilateral deafferentation of the hippocampus induced by stereotactically performed entorhinal cortex lesion (ECL). The expression of selected genes was assessed by quantitative real-time PCR in the hippocampal tissue at the injured side and the contralesional side at day 4 and 14 after injury. We observed that expression of genes coding for synaptotagmin 1, ezrin, thrombospondin 4, and C1q proteins, that have all been implicated in the synapse formation, re-arrangement and plasticity, were upregulated both in the injured and the contralesional hippocampus, implying a plasticity response in the uninjured hemisphere. Several of the genes, the expression of which was altered in response to ECL, are known to be expressed in astrocytes. To test whether astrocyte activation plays a role in the observed plasticity response to ECL, we took advantage of mice deficient in two intermediate filament (nanofilament) proteins glial fibrillary acidic protein (GFAP) and vimentin (GFAP(-/-)Vim(-/-) ) and exhibiting attenuated astrocyte activation and reactive gliosis. The absence of GFAP and vimentin reduced the ECL-induced upregulation of thrombospondin 4, indicating that this response to ECL depends on astrocyte activation and reactive gliosis. We conclude that even a very limited focal neurotrauma triggers a distinct response at the contralesional side, which at least to some extent depends on astrocyte activation.
Center for Brain Repair and Rehabilitation, Department of Clinical Neuroscience and Rehabilitation, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
Daniel
D
Andersson
Ulrika
U
Wilhelmsson
Michael
M
Nilsson
Mikael
M
Kubista
Anders
A
Ståhlberg
Marcela
M
Pekna
Milos
M
Pekny
D000344:Afferent Pathways / Q000293:injuries / Q000378:metabolism*; D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D054022:Cerebrum / Q000293:injuries / Q000378:metabolism*; D006259:Craniocerebral Trauma / Q000378:metabolism* / Q000503:physiopathology; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism; D018728:Entorhinal Cortex / Q000293:injuries / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D005904:Glial Fibrillary Acidic Protein; D006624:Hippocampus / Q000293:injuries / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics; D009473:Neuronal Plasticity; D013238:Stereotaxic Techniques; D050863:Synaptotagmin I / Q000235:genetics / Q000378:metabolism; D019699:Thrombospondins / Q000235:genetics / Q000378:metabolism; D014746:Vimentin / Q000172:deficiency / Q000235:genetics; D000099149:Ezrin
D003598:Cytoskeletal Proteins; D005904:Glial Fibrillary Acidic Protein; D009419:Nerve Tissue Proteins; D050863:Synaptotagmin I; D019699:Thrombospondins; D014746:Vimentin; D000099149:Ezrin; C494311:Syt1 protein, mouse; C528900:glial fibrillary astrocytic protein, mouse; C101864:thrombospondin 4