Spinal cord neurons are vulnerable to rapidly triggered kainate neurotoxicity in vitro

Yin, Hong-zhen; Park, David D.; Lindsay, Amy; Weiss, John H.

doi:10.1016/0006-8993(95)00532-u

Cited by 15 publications

(8 citation statements)

References 20 publications

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“…Enriched motor neuron cultures from rodent spinal cords are susceptible to toxicity when treated with NMDA (Fryer et al, 1999;Lin et al, 1998), a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and kainate (Carriedo et al, 1996;Regan, 1996;Yin et al, 1995). Though the level of cell death differs with specific culture conditions, it is generally accepted that at least a subset of motor neurons express ionotropic glutamate receptors.…”

Section: Discussionmentioning

confidence: 99%

Astroglia‐mediated effects of uric acid to protect spinal cord neurons from glutamate toxicity

Chen

Tseng

et al. 2007

Glia

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Uric acid (UA) has been demonstrated to reduce damage to neurons elicited by oxidative stress. However, our studies utilizing cultures derived from embryonic rat spinal cord indicate that an astroglia-mediated mechanism is involved in the effects of UA to protect neurons from glutamate toxicity. The damage elicted by glutamate to neurons in a mixed culture of spinal cord cells can be reversed by UA. Furthermore, addition of UA after the termination of glutamate exposure suggests that UA plays an active role in mediating neuroprotection rather than purely binding peroxynitrite, as previously thought. Importantly, in pure neuron cultures from the same tissue, UA does not protect against glutamate toxicity. Addition of astroglia to the pure neuron cultures restores the ability of UA to protect the neurons from glutamate-induced toxicity. Our results also suggest that glia provide EAAT-1 and EAAT-2 glutamate transporters to protect neurons from glutamate, that functional EAATs may be necessary to mediate the effects of UA, and that treatment with UA results in upregulation of EAAT-1 protein. Taken together, our data strongly suggest that astroglia in mixed cultures are essential for mediating the effects of UA, revealing a novel mechanism by which UA, a naturally produced substance in the body, may act to protect neurons from damage during insults such as spinal cord injury.

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Section: Discussionmentioning

confidence: 99%

Astroglia‐mediated effects of uric acid to protect spinal cord neurons from glutamate toxicity

Chen

Tseng

et al. 2007

Glia

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“…MNs have low levels of the AMPA GluR2 subunit, which results in increased calcium permeability. The molecular profile of expressed AMPA receptors may be one factor contributing to the selective vulnerability of motor neurons to excitotoxic stress (Carriedo et al, 1996;Williams et al, 1997;Yin et al, 1995). Although Wistar rats compared with Holzman rats (see section neuronal glutamate receptors) suffer greater neuronal loss following ischemic injury, there is no difference in life span when mSOD1 is expressed in the two different strains (Van Damme et al, 2007).…”

Section: Glutamate Homeostasismentioning

confidence: 98%

Astrocyte function and role in motor neuron disease: A future therapeutic target?

Blackburn

Sargsyan

Monk

et al. 2009

Glia

156

111

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Astrocytes are the most numerous cell type within the central nervous system (CNS) and perform a variety of tasks, from axon guidance and synaptic support, to the control of the blood brain barrier and blood flow. To perform these roles, there is a great variety of astrocytes. In this review, we summarize the function of astrocytes, in particular, their role in maintaining homeostasis at the synapse, regulating neuronal signaling, protecting neurons from oxidative damage, and determining the fate of endogenous neural precursors. The review also highlights recent developments indicating the role of astrocytes in motor neuron disease (MND), emphasizing their potential as therapeutic targets and agents in cell replacement therapy. The Cu-Zn superoxide dismutase (SOD1) gene that has been implicated in 20% of cases of familial MND must be expressed in the glial cells as well as motor neurons to produce the disease state in murine models of disease. Selectively reducing mutant SOD1 (mSOD1) in astrocytes does not affect disease onset but slows disease progression, whereas reducing mSOD1 in motor neurons delays disease onset and slows early disease but has less effect on life span. This suggests that glial cells represent potential therapeutic targets in MND. However, the lack of specific markers for astrocytes, their precursors, and sub-types means that our knowledge of astrocyte development/differentiation and response to injury lags far behind our understanding of function. Only by filling this knowledge gap can astrocytes be effectively targeted or replaced to successfully treat chronic CNS disorders such as MND.

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“…The agonist-induced cobalt uptake method has been used successfully to stain neurons and glial cells containing capsaicin or EAA receptors in culture, tissue explants, or brain slice preparations in a variety of animals and central nervous system (CNS) regions (Wood et al, 1988;Pruss et al, 1991;Williams et al, 1992;Nagy et al, 1994;Simmons et al, 1994;Yin et al, 1995;Zhou et al, 1995;Allcorn et al, 1996;Launey et al, 1998;Toomim and Millington, 1998;Yin et al, 1998Yin et al, , 1999Greig et al, 2000). The cobalt staining technique makes use of the fact that specific activation of EAA ionotropic receptors lacking the GluR2 subunit permits passage of divalent cations such as Ca 2ϩ into the cell.…”

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confidence: 99%

Kainate-activated cobalt uptake in the primary gustatory nucleus in goldfish: Visualization of the morphology and distribution of cells expressing AMPA/kainate receptors in the vagal lobe

2001

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Gustatory afferent fibers of the vagus nerve that innervate taste buds of the oropharynx of the goldfish, Carassius auratus, project to the vagal lobe, which is a laminated gustatory nucleus in the dorsal medulla. As in the mammalian gustatory system, responses by second-order cells in the goldfish medulla are mediated by N-methyl-D-aspartate (NMDA) and non-NMDA ionotropic glutamate receptors. We utilized a cobalt uptake technique to label vagal lobe neurons that possess cobalt-permeable ionotropic glutamate receptors. Vagal lobe slices were bathed in kainate (40 microM) or glutamate (0.5 or 1 mM) in the presence of CoCl(2), which can pass into cells through the ligand-gated cation channels of non-NMDA receptors made up of certain subunit combinations. Cobalt-filled cells and dendrites were observed in slices that were activated by kainate or glutamate, but not in control slices that were bathed in CoCl(2) alone, nor in slices that were bathed with the non-NMDA receptor antagonist 6,7-dinitroquinoxaline-2,3-dione (10 microM) in addition to an agonist. Likewise, simple depolarization of the cells with KCl failed to induce cobalt loading. Cobalt-filled round unipolar cells, elongate or globular bipolar cells, and multipolar cells with elongate or polygonal perikarya were distributed throughout the cell layers in the sensory zone of the vagal lobe. Numerous labeled neurons had dendrites spanning layers IV and VI, the two principal layers of primary afferent input. Apical and basal dendrites often extended radially through neighboring laminae, but many cells also extended dendrites tangential to the lamination of the sensory zone. In the motor layer, cell bodies and proximal dendrites of small, multipolar neurons, and large motoneurons were regularly loaded with cobalt.

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Spinal cord neurons are vulnerable to rapidly triggered kainate neurotoxicity in vitro

Cited by 15 publications

References 20 publications

Astroglia‐mediated effects of uric acid to protect spinal cord neurons from glutamate toxicity

Astroglia‐mediated effects of uric acid to protect spinal cord neurons from glutamate toxicity

Astrocyte function and role in motor neuron disease: A future therapeutic target?

Kainate-activated cobalt uptake in the primary gustatory nucleus in goldfish: Visualization of the morphology and distribution of cells expressing AMPA/kainate receptors in the vagal lobe

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