Chondroitin Sulfate Proteoglycan and Tenascin in the Wounded Adult Mouse NeostriatumIn Vitro: Dopamine Neuron Attachment and Process Outgrowth

Abstract

Extracellular matrix (ECM) molecules, including chondroitin-4 or chondroitin-6 sulfate proteoglycans (CSPGs) and tenascin, are upregulated in and around wounds and transplants to the adult CNS. In the present study, striatal wounds from adult mice were used in a novel in vitro paradigm to assess the effects of these wound-associated molecules on embryonic dopamine cell attachment and neurite outgrowth. Light and electron microscopic immunocytochemistry studies have shown that astroglial scar constituents persist in cultured explants for at least 1 week in vitro, and despite the loss of neurons from adult striatal explants, there is a retention of certain structural features suggesting that the wound explant-neuron coplant is a viable model for analysis of graft-scar interactions. Explants from the wounded striatum taken at different times after a penetrating injury in vivo were used as substrates for embryonic ventral mesencephalon neurons that were plated on their surfaces. Dopamine cell attachment is increased significantly in relation to the expression of both CSPG and tenascin. The increase in neuronal attachment in this paradigm, however, is accompanied by a postlesion survival time-dependent significant decrease in neuritic growth from these cells. In vitro ECM antibody treatment suggests that CSPG may be responsible for heightened dopamine cell attachment and that tenascin simultaneously may support cell attachment while inhibiting neurite growth. The present study offers a new approach for the in vitro analysis of cell and molecular interactions after brain injury and brain grafting, in essence acting as a nigrostriatal transplant-in-a-dish.

The Adult Mouse Subependymal Zone Regenerates Efficiently in the Absence of Tenascin-C

“…1). Although expression of TnC bordering areas of dynamic cell movements and interactions has been well documented during development (Steindler et al, 1995) and after injury (Laywell et al, 1992;Gates et al, 1996;Nishio et al, 2005), its role remains elusive (Nishio et al, 2005). The only difference we detected within the SEZ of the TnC deficient mice was the increased number of type-A cell clusters along the LV wall.…”

“…Tenascin-C (TnC) is a large ECM glycoprotein (Jones and Jones, 2000) that is expressed in the brain neurogenic zones during development (Steindler et al, 1995;Garcion et al, 2004) and postnatally (Thomas et al, 1996;Garcion et al, 2001;Peretto et al, 2005;Bonnert et al, 2006;de Chevigny et al, 2006) as well as in areas of plasticity (i.e., after injury) in the adult brain (Laywell et al, 1992;Gates et al, 1996;Nishio et al, 2005). This expression profile combined with results using TnC null mice showing a role for TnC in the proliferation and migration of early postnatal neural precursors (Garcion et al, 2001) and the growth-factor responsiveness of embryonic neural stem cells (NSC) (Garcion et al, 2004) led us to ask whether TnC also plays a role in adult neurogenesis.…”

Preservation of glial cytoarchitecture from ex vivo human tumor and non-tumor cerebral cortical explants: A human model to study neurological diseases

“…It also remains to be studied whether the neurons from normal cortical explants can be maintained for longer periods of time. Prior studies using rodent explants used serum-free media and media supplemented with neurotrophic factors to increase the viability of neurons, which may also be applicable in human cortical explants (Benninger et al 2003;Gates et al 1996;Kearns et al 2006). …”

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

“…Of these, the role of CSPGs in mammalian CNS injury and plasticity has been the subject of intense investigation (Carulli et al, 2005). The production of CSPGs by astrocytes is rapidly upregulated after CNS injury, and their deposition in the ECM forms a major component of the glial scar that serves to prevent axon regeneration (McKeon et al, 1991;Gates et al, 1996;Davies et al, 1997Davies et al, , 1999Fitch and Silver, 1997). In vitro, CSPGs alone are inhibitory to neurite extension and can present a boundary to growing axons (Snow et al, 1990).…”