Dataset Information

Differential distribution of aggrecan isoforms in perineuronal nets of the human cerebral cortex.

ABSTRACT: Aggrecan is a component of the CNS extracellular matrix (ECM) and we show here that the three primary alternative spliced transcripts of the aggrecan gene found in cartilage are also present in the adult CNS. Using a unique panel of core protein-directed antibodies against human aggrecan we further show that different aggrecan isoforms are deposited in perineuronal nets (PNNs) and neuropil ECM of Brodmann's area 6 of the human adult cerebral cortex. According to their distribution pattern, the identified cortical aggrecan isoforms were subdivided into five clusters spanning from cluster 1, comprised isoforms that appeared widespread throughout the cortex, to cluster 5, which was an aggrecan-free subset. Comparison of brain and cartilage tissues showed a different relative abundance of aggrecan isoforms, with cartilage-specific isoforms characterizing cluster 5, and PNN-associated isoforms lacking keratan sulphate chains. In the brain, isoforms of cluster 1 were disclosed in PNNs surrounding small-medium interneurons of layers II-V, small-medium pyramidal neurons of layers III and V and large interneurons of layer VI. Aggrecan PNNs enveloped both neuron bodies and neuronal processes, encompassing pre-terminal nerve fibres, synaptic boutons and terminal processes of glial cells and aggrecan was also observed in continuous 'coats' associated with satellite, neuron-associated cells of a putative glial nature. Immunolabelling for calcium-binding proteins and glutamate demonstrated that aggrecan PNNs were linked to defined subsets of cortical interneurons and pyramidal cells. We suggest that in the human cerebral cortex, discrete, layer-specific PNNs are assembled through the participation of selected aggrecan isoforms that characterize defined subsets of cortical neurons.

SUBMITTER: Virgintino D

PROVIDER: S-EPMC4516474 | biostudies-literature | 2009 Sep

REPOSITORIES: biostudies-literature

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Differential distribution of aggrecan isoforms in perineuronal nets of the human cerebral cortex.

Virgintino Daniela D Perissinotto Daniela D Girolamo Francesco F Mucignat Maria T MT Montanini Luisa L Errede Mariella M Kaneiwa Tomoyuki T Yamada Shushei S Sugahara Kazuyuki K Roncali Luisa L Perris Roberto R

Journal of cellular and molecular medicine 20090209 9B

Aggrecan is a component of the CNS extracellular matrix (ECM) and we show here that the three primary alternative spliced transcripts of the aggrecan gene found in cartilage are also present in the adult CNS. Using a unique panel of core protein-directed antibodies against human aggrecan we further show that different aggrecan isoforms are deposited in perineuronal nets (PNNs) and neuropil ECM of Brodmann's area 6 of the human adult cerebral cortex. According to their distribution pattern, the i ...[more]

PMID: 19220578

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Project description:Stroke causes life long disabilities where few therapeutic options are available. Using electrical and magnetic stimulation of the brain and physical rehabilitation, recovery of brain function can be enhanced even late after stroke. Animal models support this notion, and housing rodents in an enriched environment (EE) several days after experimental stroke stimulates lost brain function by multisensory mechanisms. We studied the dynamics of functional recovery of rats with a lesion to the fore and hind limb motor areas induced by photothrombosis (PT), and with subsequent housing in either standard (STD) or EE. In this model, skilled motor function is not significantly enhanced by enriched housing, while the speed of recovery of sensori-motor function substantially improves over the 9-week study period. In particular, this stroke lesion completely obliterates the fore and hind limb placing ability when visual and whisker guidance is prevented, a deficit that persists for up to 9 weeks of recovery, but that is markedly restored within 2 weeks by enriched housing. Enriched housing after stroke also leads to a significant loss of perineuronal net (PNN) immunoreactivity; detection of aggrecan protein backbone with AB1031 antibody was decreased by 13-22%, and labelling of a glycan moiety of aggrecan with Cat-315 antibody was reduced by 25-30% in the peri-infarct area and in the somatosensory cortex, respectively. The majority of these cells are parvalbumin/GABA inhibitory interneurons that are important in sensori-information processing. We conclude that damage to the fore and hind limb motor areas provides a model of loss of limb placing response without visual guidance, a deficit also seen in more than 50% of stroke patients. This loss is amenable to recovery induced by multiple sensory stimulation and correlates with a decrease in aggrecan-containing PNNs around inhibitory interneurons. Modulating the PNN structure after ischemic damage may provide new therapies enhancing tactile/proprioceptive function after stroke.

Project description:Using intracranial electrocorticography, we determined how cortical gamma-oscillations (50-150 Hz) were induced by different visual tasks in nine children with focal epilepsy. In all children, full-field stroboscopic flash-stimuli induced gamma-augmentation in the anterior-medial occipital cortex (starting on average at 31 ms after stimulus presentation) and subsequently in the lateral-polar occipital cortex; minimal gamma-augmentation was noted in the inferior occipital-temporal cortex; occipital gamma-augmentation was followed by gamma-attenuation in three children. Central-field picture-stimuli induced sustained gamma-augmentation in the lateral-polar occipital cortex (starting on average at 69 ms) and subsequently in the inferior occipital-temporal cortex in all children and in the posterior frontal cortex in three children; the anterior-medial occipital cortex showed no gamma-augmentation but rather gamma-attenuation. Electrical stimulation of the anterior-medial occipital cortex induced a phosphene in the peripheral-field or eye deviation to the contralateral side, whereas that of the lateral-polar occipital cortex induced a phosphene in the central-field. In summary, full-field, simple and short-lasting visual information might be preferentially processed by the anterior-medial occipital cortex, and subsequently by the lateral-polar occipital cortex. Gamma-attenuation following augmentation in the striate cortex might be associated with a relative refractory-period to flash-stimuli or feed-forward inhibition by other areas. Central-field complex visual information might be processed by a network involving the lateral-polar occipital cortex and the inferior occipital-temporal cortex. A plausible interpretation of posterior frontal gamma-augmentation during central-field picture stimuli includes activation of the frontal-eye-field for visual searching. Gamma-attenuation in the anterior-medial occipital cortex during central-field picture-stimuli might be associated with relative inattention to the peripheral visual field during central-field object visualization.

Dataset Information

Differential distribution of aggrecan isoforms in perineuronal nets of the human cerebral cortex.

Publications

Differential distribution of aggrecan isoforms in perineuronal nets of the human cerebral cortex.

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