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Relationship between white matter integrity and severity of motor impairment in children with cerebral palsy caused by periventricular leukomalacia
Abstracts / Int. J. Devl Neuroscience 47 (2015) 1–131
formed on 0.5%wt/v CS1 or CS2 peptides and NFs were present in all conditions (Fig. 1). MALDI was used to determine enzymatic activity through product formation after incubating the peptide matrices with active MMP-2, and visible product fragments were observed. Neurogenesis, hypoxic cell mortality, and glial attenuation in response to neuropeptide release were observed using PC-12 neurons, primary cortical neuron, and microglia culture. Cortical neurons were exposed to DGGL and MVG product fragments. Bothe peptides induced neurite outgrowth in PC-12 cells. The MVG analogues promoted survival of neurons, observed by MMT assay. PC-12 cells and microglia were seeded into (RADA)4 -IKAV/(RADA)4 mixtures and 90% (RADA)4 displayed optimal adhesion for both cell types, observed using inverted fluorescent microscopy (Fig. 2). http://dx.doi.org/10.1016/j.ijdevneu.2015.04.314 ISDN2014 0396 Dystroglycan is a critical regulator of forebrain connectivity K.M. Wright 1,3,4,∗ , K. Lyon 1,2,3 , D. Ginty 1,2,3 1 Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, United States 2 Department of Neurobiology, Harvard Medical School, Boston, MA, United States 3 Howard Hughes Medical Institute, United States 4 Vollum Institute, Oregon Health & Science University, Portland, OR, United States E-mail address: [email protected] (K.M. Wright).
During neural circuit development, instructive extracellular cues signal through cell surface receptors to direct the precise targeting of axons, elaboration of dendritic arbors and the formation of synapses. Due to the complexity of the connections that form neural circuits, our understanding of the molecular pathways involved in these processes remains incomplete. In a forward genetic screen for novel regulators of axon guidance, we identified mutations in B3gnt1 and ISPD, two enzymes required for the glycosylation of the glycoprotein dystroglycan. Analysis of dystroglycan mutant mice reveals that dystroglycan functions as a critical regulator of axon guidance and neuronal morphology during forebrain development. Dystroglycan mutants exhibit severe disruptions in the formation of the internal capsule, with both corticothalamic and thalamocortical axons exhibiting abnormal trajectories. In addition, cortical migration and dendritic arborization are significantly affected in these mutants. These phenotypes bear striking resemblance to mice lacking the planar cell polarity (PCP) genes Celsr3 and Fzd3. Celsr3 contains two Laminin G domains, a motif that is present in known dystroglycan binding proteins, providing a potential mechanistic link between dystroglycan and Celsr3. These results suggest that dystroglycan coordinates axon guidance and dendritic arborization by interacting with the PCP pathway during forebrain development. http://dx.doi.org/10.1016/j.ijdevneu.2015.04.315
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ISDN2014 0397 Relationship between white matter integrity and severity of motor impairment in children with cerebral palsy caused by periventricular leukomalacia M. Kim ∗ , J.S. Shim, J.Y. Song CHA University, Republic of Korea E-mail address: [email protected] (M. Kim). Diffusion tensor imaging (DTI) is an imaging technique that provides visualization and quantitative measurement of white matter integrity. We extracted the quantitative data from DTI of children with cerebral palsy (CP) caused by periventricular leukomalacia (PVL) and evaluated its relationship with impairment. The Gross Motor Function Classification System (GMFCS) that focuses on ambulatory ability and the Bayley Scales of Infant Development-II (BSID-II) were used for function measure. We obtained DTI data from 114 children with CP (38.8 ± 16.3 months). The inclusion criteria were ages between 12 and 71 months; diagnosis of PVL in brain MRI; and no other causes for delayed development. GMFCS and BSID-II were assessed by specialists after establishing inter and intra-rater reliability. The DTI data were analyzed with DTI studio after Eddy current correction. Common DTI parameters including fiber number and region of interest (ROI)-based fractional anisotropy (FA) were measured for corticospinal tract at posterior limb of internal capsule (PLIC) and ascending sensory tract (AST) at pons. The ROIs in PLIC were divided to anteromedial and posterolateral parts. There were no significant differences of FA values for GMFCS difference of one level. However, the mildly impaired group of GMFCS level I to III showed higher FA values compared to the severely impaired group of GMFCS level IV and V in all PLIC areas (ps < 0.05). FA values in bilateral posterolateral parts of PLIC showed negative correlations according to GMFCS levels (rs < −0.40, ps < 0.01) and BSID-II motor raw scores (rs < −0.36, ps < 0.01), while those of AST did not. Fiber numbers of bilateral CST showed weak negative correlation with GMFCS (rs < −0.29, ps < 0.03). Since somatotopy s preserved in the PLIC, integrity of posterolateral PLIC seems to have significant correlation to the degree of ambulatory ability. When cautiously measured, DTI parameters may be used as an important parameter to assess severity in children with CP. http://dx.doi.org/10.1016/j.ijdevneu.2015.04.316 ISDN2014 0398 Corpus callosum abnormalities in medication-naïve adult patients with obsessive compulsive disorder Dania Jose, Janardhanan C. Narayanaswamy, Sri Mahavir Agarwal, Sunil Kalmady, Ganesan Venkatasubramanian ∗ , Y.C. Janardhan Reddy Obsessive Compulsive Disorder Clinic, Department of Psychiatry & Translational Psychiatry Laboratory, Neurobiology Research Centre, National Institute of Mental Health and Neurosciences, Bangalore, India Introduction: Emerging evidence demonstrates widespread involvement of white matter tracts connecting different cortical areas in Obsessive Compulsive Disorder (OCD), indicating that the pathophysiology may lie in the white matter (WM) abnormalities. Corpus callosum (CC) – the largest inter-hemispheric tract connecting the association cortices – has been shown to be affected in OCD.
formed on 0.5%wt/v CS1 or CS2 peptides and NFs were present in all conditions (Fig. 1). MALDI was used to determine enzymatic activity through product formation after incubating the peptide matrices with active MMP-2, and visible product fragments were observed. Neurogenesis, hypoxic cell mortality, and glial attenuation in response to neuropeptide release were observed using PC-12 neurons, primary cortical neuron, and microglia culture. Cortical neurons were exposed to DGGL and MVG product fragments. Bothe peptides induced neurite outgrowth in PC-12 cells. The MVG analogues promoted survival of neurons, observed by MMT assay. PC-12 cells and microglia were seeded into (RADA)4 -IKAV/(RADA)4 mixtures and 90% (RADA)4 displayed optimal adhesion for both cell types, observed using inverted fluorescent microscopy (Fig. 2). http://dx.doi.org/10.1016/j.ijdevneu.2015.04.314 ISDN2014 0396 Dystroglycan is a critical regulator of forebrain connectivity K.M. Wright 1,3,4,∗ , K. Lyon 1,2,3 , D. Ginty 1,2,3 1 Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, United States 2 Department of Neurobiology, Harvard Medical School, Boston, MA, United States 3 Howard Hughes Medical Institute, United States 4 Vollum Institute, Oregon Health & Science University, Portland, OR, United States E-mail address: [email protected] (K.M. Wright).
During neural circuit development, instructive extracellular cues signal through cell surface receptors to direct the precise targeting of axons, elaboration of dendritic arbors and the formation of synapses. Due to the complexity of the connections that form neural circuits, our understanding of the molecular pathways involved in these processes remains incomplete. In a forward genetic screen for novel regulators of axon guidance, we identified mutations in B3gnt1 and ISPD, two enzymes required for the glycosylation of the glycoprotein dystroglycan. Analysis of dystroglycan mutant mice reveals that dystroglycan functions as a critical regulator of axon guidance and neuronal morphology during forebrain development. Dystroglycan mutants exhibit severe disruptions in the formation of the internal capsule, with both corticothalamic and thalamocortical axons exhibiting abnormal trajectories. In addition, cortical migration and dendritic arborization are significantly affected in these mutants. These phenotypes bear striking resemblance to mice lacking the planar cell polarity (PCP) genes Celsr3 and Fzd3. Celsr3 contains two Laminin G domains, a motif that is present in known dystroglycan binding proteins, providing a potential mechanistic link between dystroglycan and Celsr3. These results suggest that dystroglycan coordinates axon guidance and dendritic arborization by interacting with the PCP pathway during forebrain development. http://dx.doi.org/10.1016/j.ijdevneu.2015.04.315
117
ISDN2014 0397 Relationship between white matter integrity and severity of motor impairment in children with cerebral palsy caused by periventricular leukomalacia M. Kim ∗ , J.S. Shim, J.Y. Song CHA University, Republic of Korea E-mail address: [email protected] (M. Kim). Diffusion tensor imaging (DTI) is an imaging technique that provides visualization and quantitative measurement of white matter integrity. We extracted the quantitative data from DTI of children with cerebral palsy (CP) caused by periventricular leukomalacia (PVL) and evaluated its relationship with impairment. The Gross Motor Function Classification System (GMFCS) that focuses on ambulatory ability and the Bayley Scales of Infant Development-II (BSID-II) were used for function measure. We obtained DTI data from 114 children with CP (38.8 ± 16.3 months). The inclusion criteria were ages between 12 and 71 months; diagnosis of PVL in brain MRI; and no other causes for delayed development. GMFCS and BSID-II were assessed by specialists after establishing inter and intra-rater reliability. The DTI data were analyzed with DTI studio after Eddy current correction. Common DTI parameters including fiber number and region of interest (ROI)-based fractional anisotropy (FA) were measured for corticospinal tract at posterior limb of internal capsule (PLIC) and ascending sensory tract (AST) at pons. The ROIs in PLIC were divided to anteromedial and posterolateral parts. There were no significant differences of FA values for GMFCS difference of one level. However, the mildly impaired group of GMFCS level I to III showed higher FA values compared to the severely impaired group of GMFCS level IV and V in all PLIC areas (ps < 0.05). FA values in bilateral posterolateral parts of PLIC showed negative correlations according to GMFCS levels (rs < −0.40, ps < 0.01) and BSID-II motor raw scores (rs < −0.36, ps < 0.01), while those of AST did not. Fiber numbers of bilateral CST showed weak negative correlation with GMFCS (rs < −0.29, ps < 0.03). Since somatotopy s preserved in the PLIC, integrity of posterolateral PLIC seems to have significant correlation to the degree of ambulatory ability. When cautiously measured, DTI parameters may be used as an important parameter to assess severity in children with CP. http://dx.doi.org/10.1016/j.ijdevneu.2015.04.316 ISDN2014 0398 Corpus callosum abnormalities in medication-naïve adult patients with obsessive compulsive disorder Dania Jose, Janardhanan C. Narayanaswamy, Sri Mahavir Agarwal, Sunil Kalmady, Ganesan Venkatasubramanian ∗ , Y.C. Janardhan Reddy Obsessive Compulsive Disorder Clinic, Department of Psychiatry & Translational Psychiatry Laboratory, Neurobiology Research Centre, National Institute of Mental Health and Neurosciences, Bangalore, India Introduction: Emerging evidence demonstrates widespread involvement of white matter tracts connecting different cortical areas in Obsessive Compulsive Disorder (OCD), indicating that the pathophysiology may lie in the white matter (WM) abnormalities. Corpus callosum (CC) – the largest inter-hemispheric tract connecting the association cortices – has been shown to be affected in OCD.