Chondroitin sulphate proteoglycans: preventing plasticity or protecting the CNS?

Rhodes, Kate; Fawcett, James W.

doi:10.1111/j.1469-7580.2004.00261.x

Cited by 258 publications

(172 citation statements)

References 206 publications

Supporting

Mentioning

164

Contrasting

Unclassified

Order By: Relevance

“…This observation is consistent with the theory that PNNs may be necessary to provide the cytoskeletal and metabolic support necessary to large, highly active neurons (Celio and Blumcke, 1994). It has been suggested that, while providing such support, PNN may stabilize existing synaptic contacts and prevent the formation of new ones (Hockfield and Kalb, 1993;Celio and Blumcke, 1994;Yamaguchi, 2000;Rhodes and Fawcett, 2004). It is thus possible that neurons wrapped in PNNs, including PVB/PNN/-and PVB/PNN/CB neurons in the human BLC-CO, may have limited synaptic plasticity.…”

Section: Relationship Between Pvb and Pnns In The Human Amygdalasupporting

confidence: 79%

Subpopulations of neurons expressing parvalbumin in the human amygdala

Pantazopoulos

Lange

Hassinger

et al. 2006

J of Comparative Neurology

View full text Add to dashboard Cite

Amygdalar intrinsic inhibitory networks comprise several subpopulations of γ-aminobutyric acidergic neurons, each characterized by distinct morphological features and clusters of functionally relevant neurochemical markers. In rodents, the calcium-binding proteins parvalbumin (PVB) and calbindin D28k (CB) are coexpressed in large subpopulations of amygdalar interneurons. PVBimmunoreactive (-IR) neurons have also been shown to be ensheathed by perineuronal nets (PNN), extracellular matrix envelopes believed to affect ionic homeostasis and synaptic plasticity. We tested the hypothesis that differential expression of these three markers may define distinct neuronal subpopulations within the human amygdala. Toward this end, triple-fluorescent labeling using antisera raised against PVB and CB as well as biotinylated Wisteria floribunda lectin for detection of PNN was combined with confocal microscopy. Among the 1,779 PVB-IR neurons counted, 18% also expressed CB, 31% were ensheathed in PNN, and 7% expressed both CB and PNN. Forty-four percent of PVB-IR neurons did not colocalize with either CB or PNN. The distribution of each of these neuronal subgroups showed substantial rostrocaudal gradients. Furthermore, distinct morphological features were found to characterize each neuronal subgroup. In particular, significant differences relative to the distribution and morphology were detected between PVB-IR neurons expressing CB and PVB-IR neurons wrapped in PNNs. These results indicate that amygdalar PVB-IR neurons can be subdivided into at least four different subgroups, each characterized by a specific neurochemical profile, morphological characteristics, and three-dimensional distribution. Such properties suggest that each of these neuronal subpopulations may play a specific role within the intrinsic circuitry of the amygdala. Keywordscalbindin D28k; perineuronal nets; immunocytochemistry; confocal microscopy; basolateral complex of the amygdala The basolateral complex of the amygdala (lateral, basolateral, and accessory basal nuclei; BLC) plays an important role in assigning affective and motivational significance to sensory inputs, forming emotional memories, and generating emotional responses (Gloor, 1986;Halgren, 1992;Brothers, 1990;LeDoux, 1992;Aggleton, 1993;Adolphs et al., 1994). Complex intrinsic inhibitory circuits are believed to represent a critical component of the neural networks NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript underlying these functions. Among the several subpopulations of interneurons forming these circuits, those expressing the calcium-binding protein parvalbumin (PVB) are localized preferentially within the BLC (Sorvari et al., 1995). These neurons have been shown to affect information processing in this region crucially. For instance, the extremely low spontaneous firing rates typical of BLC projection neurons are thought to be the result of strong intrinsic inhibitory pressures originating from PVB-immunoreactive (-IR) neurons (Rainnie et al., 1991;Par...

show abstract

Section: Relationship Between Pvb and Pnns In The Human Amygdalasupporting

confidence: 79%

Subpopulations of neurons expressing parvalbumin in the human amygdala

Pantazopoulos

Lange

Hassinger

et al. 2006

J of Comparative Neurology

View full text Add to dashboard Cite

show abstract

“…Conversely, increased ADAMTS mediated CSPG degradation may potentiate brain injury and enable infiltration of inflammatory cells [14], [33].…”

Section: Discussionmentioning

confidence: 99%

ADAMTS-1 and -4 are up-regulated following transient middle cerebral artery occlusion in the rat and their expression is modulated by TNF in cultured astrocytes

et al. 2006

View full text Add to dashboard Cite

ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) enzymes are a recently described group of metalloproteinases. The substrates degraded by ADAMTS-1, -4 and -5 suggests that they play a role in turnover of extracellular matrix in the central nervous system (CNS). ADAMTS-1 is also known to exhibit anti-angiogenic activity. Their main endogenous inhibitor is tissue inhibitor of metalloproteinases (TIMP)-3.The present study was designed to investigate ADAMTS-1, -4 and -5 and TIMP-3 expression after experimental cerebral ischaemia and to examine whether cytokines known to be up-regulated in stroke could alter their expression by astrocytes in vitro.Focal cerebral ischaemia was induced by transient middle cerebral artery occlusion in the rat using the filament method.Our results demonstrate a significant increase in expression of ADAMTS-1 and -4 in the occluded hemisphere but no significant change in TIMP-3. This was accompanied by an increase in mRNA levels for interleukin (IL)-1β, IL-1 receptor antagonist (IL1ra) and tumour necrosis factor (TNF). ADAMTS-4 mRNA and protein was upregulated by TNF in primary human astrocyte cultures. The increased ADAMTS-1 and -4 in experimental stroke, together with no change in TIMP-3, may promote ECM breakdown after stroke, enabling infiltration of inflammatory cells and contribute to brain injury. In vitro studies suggest that the in vivo modulation of ADAMTS-1 and -4 may be controlled in part by TNF.3

show abstract

“…Recent experiments have shown that a single injection of cABC can prevent a rise in GAG for up to a week (Lin et al, 2007), so the blockade of synthesis can be delayed for several days after injury. The other major effect of CSPGs in the CNS is in the control of plasticity, and removal of GAGs with cABC can enhance plasticity in the adult CNS (Pizzorusso et al, 2002;Rhodes and Fawcett, 2004). Reducing GAG synthesis may be an alternative method of producing longer-term increases in plasticity, which could be helpful in a range of CNS disorders.…”

Section: Discussionmentioning

confidence: 99%

Inhibiting Glycosaminoglycan Chain Polymerization Decreases the Inhibitory Activity of Astrocyte-Derived Chondroitin Sulfate Proteoglycans

Laabs

Wang²,

Katagiri³

et al. 2007

J. Neurosci.

Self Cite

109

101

View full text Add to dashboard Cite

Chondroitin sulfate proteoglycans (CSPGs) are upregulated in the CNS after injury and participate in the inhibition of axon regeneration mainly through their glycosaminoglycan (GAG) side chains. In the present study, we have identified a new way to alleviate the inhibition of axonal regeneration by CSPG GAGs. We have successfully decreased the amount of CSPG GAG produced by astrocytes by targeting chondroitin polymerizing factor (ChPF), a key enzyme in the CSPG biosynthetic pathway. Using short interfering RNA (siRNA), we reduced ChPF mRNA levels by 70% in both the Neu7 astrocyte cell line and primary rat astrocytes. This reduction leads to a decrease in ChPF protein levels and a reduced amount of CSPG GAG chains in the conditioned media (CM) of these cells. Secretion of neurocan by primary astrocytes and NG2 core protein by Neu7 cells transfected with ChPF siRNA is not decreased, suggesting that inhibiting GAG chain synthesis does not affect core protein trafficking from these cells. CM from siRNA-treated Neu7 cells is a less repulsive substrate for axons than CM from control cells. In addition, axonal outgrowth from cerebellar granule neurons is increased on or in CM from ChPF siRNA-treated Neu7 cells. These data indicate that targeting the biosynthesis of CSPG GAG is a potentially new therapeutic avenue for decreasing CSPG GAG produced by astrocytes after CNS injury.

show abstract

Chondroitin sulphate proteoglycans: preventing plasticity or protecting the CNS?

Cited by 258 publications

References 206 publications

Subpopulations of neurons expressing parvalbumin in the human amygdala

Subpopulations of neurons expressing parvalbumin in the human amygdala

ADAMTS-1 and -4 are up-regulated following transient middle cerebral artery occlusion in the rat and their expression is modulated by TNF in cultured astrocytes

Inhibiting Glycosaminoglycan Chain Polymerization Decreases the Inhibitory Activity of Astrocyte-Derived Chondroitin Sulfate Proteoglycans

Contact Info

Product

Resources

About