Deep brain stimulation of the ventromedial prefrontal cortex causes reorganization of neuronal processes and vasculature
Por:
Chakravarty M.M., Hamani C., Martinez-Canabal A., Ellegood J., Laliberté C., Nobrega J.N., Sankar T., Lozano A.M., Frankland P.W., Lerch J.P.
Publicada:
1 ene 2016
Resumen:
Background: Chronic high-frequency electrical deep brain stimulation (DBS) of the subcallosal cingulate region is currently being investigated clinically as a therapy for treatment of refractory depression. Experimental DBS of the homologous region, the ventromedial prefrontal cortex (VMPFC), in rodent models has previously demonstrated anti-depressant-like effects. Our goal was to determine if structural remodeling accompanies the alterations of brain function previously observed as a result of chronic DBS. Methods: Here we applied 6. h of high-frequency bilateral VMPFC DBS daily to 8 9-week old C57Bl/6 mice for 5. days. We investigated the "micro-lesion" effect by using a sham stimulation group (8 mice) and a control group (8 mice with a hole drilled into the skull only). Whole brain anatomy was investigated post-mortem using high-resolution magnetic resonance imaging and areas demonstrating volumetric expansion were further investigated using histology and immunohistochemistry. Results: The DBS group demonstrated bilateral increases in whole hippocampus and the left thalamus volume compared to both sham and control groups. Local hippocampal and thalamic volume increases were also observed at the voxel-level; however these increases were observed in both DBS and sham groups. Follow-up immunohistochemistry in the hippocampus revealed DBS increased blood vessel size and synaptic density relative to the control group whereas the sham group demonstrated increased astrocyte size. Conclusions: Our work demonstrates that DBS not only works by altering function with neural circuits, but also by structurally altering circuits at the cellular level. Neuroplastic alterations may play a role in mediating the clinical efficacy of DBS therapy. © 2015 Published by Elsevier Inc.
Filiaciones:
Chakravarty M.M.:
Cerebral Imaging Centre, Douglas Mental Health University Institute, Canada
Department of Psychiatry, McGill University, Canada
Department of Biomedical Engineering, McGill University, Canada
Hamani C.:
Division of Neurosurgery, Toronto Western Hospital, Canada
Behavioural Neurobiology Laboratory, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Canada
Martinez-Canabal A.:
Program in Neuroscience and Mental Health, The Hospital for Sick Children, Canada
Ellegood J.:
Mouse Imaging Centre (MICe), The Hospital for Sick Children, Canada
Laliberté C.:
Mouse Imaging Centre (MICe), The Hospital for Sick Children, Canada
Nobrega J.N.:
Department of Psychiatry, University of Toronto, Canada
Behavioural Neurobiology Laboratory, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Canada
Sankar T.:
Division of Neurosurgery, Toronto Western Hospital, Canada
Division of Neurosurgery, University of Alberta, Canada
Lozano A.M.:
Division of Neurosurgery, Toronto Western Hospital, Canada
Frankland P.W.:
Program in Neuroscience and Mental Health, The Hospital for Sick Children, Canada
Department of Psychology, University of Toronto, Toronto, Canada
Department of Physiology, University of Toronto, Toronto, Canada
Institute of Medical Science, University of Toronto, Toronto, Canada
Lerch J.P.:
Program in Neuroscience and Mental Health, The Hospital for Sick Children, Canada
Mouse Imaging Centre (MICe), The Hospital for Sick Children, Canada
Department of Medical Biophysics, University of Toronto, Canada
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