| Autor: |
van de Vondervoort IIGM; Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands. ilsevandevondervoort@gmail.com., Amiri H; Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands.; Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran.; Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands., Bruchhage MMK; Centre for Neuroimaging Sciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK., Oomen CA; Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands.; Centre for Neuroscience, Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, The Netherlands.; Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, VU University Amsterdam, Amsterdam, The Netherlands., Rustogi N; Cambridge Centre for Neuropsychiatric Research, Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, UK., Cooper JD; Cambridge Centre for Neuropsychiatric Research, Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, UK., van Asten JJA; Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands., Heerschap A; Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands., Bahn S; Cambridge Centre for Neuropsychiatric Research, Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, UK., Williams SCR; Centre for Neuroimaging Sciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.; MRC Centre for Neurodevelopmental Disorders, King's College London, London, UK., Buitelaar JK; Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands.; Karakter Child and Adolescent Psychiatry University Centre, Nijmegen, The Netherlands., Poelmans G; Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.; Department of Molecular Animal Physiology, Donders Institute for Brain, Cognition and Behaviour, Radboud Institute for Molecular Life Sciences (RIMLS), Radboud University, Nijmegen, The Netherlands., Glennon JC; Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands. |
| Abstrakt: |
Obsessive-compulsive disorder (OCD) is a neuropsychiatric disorder with childhood onset, and is characterized by intrusive thoughts and fears (obsessions) that lead to repetitive behaviors (compulsions). Previously, we identified insulin signaling being associated with OCD and here, we aim to further investigate this link in vivo. We studied TALLYHO/JngJ (TH) mice, a model of type 2 diabetes mellitus, to (1) assess compulsive and anxious behaviors, (2) determine neuro-metabolite levels by 1 H magnetic resonance spectroscopy (MRS) and brain structural connectivity by diffusion tensor imaging (DTI), and (3) investigate plasma and brain protein levels for molecules previously associated with OCD (insulin, Igf1, Kcnq1, and Bdnf) in these subjects. TH mice showed increased compulsivity-like behavior (reduced spontaneous alternation in the Y-maze) and more anxiety (less time spent in the open arms of the elevated plus maze). In parallel, their brains differed in the white matter microstructure measures fractional anisotropy (FA) and mean diffusivity (MD) in the midline corpus callosum (increased FA and decreased MD), in myelinated fibers of the dorsomedial striatum (decreased FA and MD), and superior cerebellar peduncles (decreased FA and MD). MRS revealed increased glucose levels in the dorsomedial striatum and increased glutathione levels in the anterior cingulate cortex in the TH mice relative to their controls. Igf1 expression was reduced in the cerebellum of TH mice but increased in the plasma. In conclusion, our data indicates a role of (abnormal) insulin signaling in compulsivity-like behavior. |
