Synaptic reorganization by mossy fibers in human epileptic fascia dentata

Babb, Thomas L.; Kupfer, William; Pretorius, James K.; Crandall, Paul H.; Lévesque, Michel

doi:10.1016/0306-4522(91)90380-7

Cited by 627 publications

(353 citation statements)

References 47 publications

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“…In the epileptic brain of both humans with TLE and animal models of TLE, MFs reorganize and innervate new targets in the inner molecular layer of the dentate gyrus (17)(18)(19)(20). Targets for these sprouted terminals include both DGCs and inhibitory interneurons (21,22).…”

Section: Mossy Fiber Sproutingmentioning

confidence: 99%

Mossy Fiber Zinc and Temporal Lobe Epilepsy: Pathological Association with Altered “Epileptic”γ‐Aminobutyric Acid A Receptors in Dentate Granule Cells

Coulter

2000

Epilepsia

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Summary:Temporal lobe epilepsy is associated with circuit rearrangements within the hippocampus. Mossy fibers sprout and pathologically innervate the inner molecular layer of the dentate gyrus, providing a recurrent excitatory pathway not present in the control brain. In addition to releasing glutamate, these recurrent collaterals also release zinc, which can accumulate in high concentrations in the extracellular space. Accompanying these dentate gyrus circuit rearrangements are alterations in the subunit expression patterns and pharmacology of y-aminobutyric acid A (GABA,) receptors in dentate granule cells. In normal, control granule cells, GABA, receptors are zinc insensitive as a result of high levels of expression of the a1 subunit in these cells. In epileptic brain, expression of a1 subunits decreases and expression of a4 and 6 subunits increases, leading to the assembly of GABA, receptors that are exquisitely zinc sensitive. This temporal and spatial association of the expression of zinc-sensitive GABA, receptors and the emergence of a zinc-delivery system unique to the epileptic hippocampus has led to the formulation of an hypothesis that suggests that zinc release during repetitive activation of the dentate gyms may lead to a catastrophic failure of inhibition under conditions mediating seizure initiation. This could contribute to the limbic hyperexcitability characteristic of temporal lobe epilepsy.

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Section: Mossy Fiber Sproutingmentioning

confidence: 99%

Mossy Fiber Zinc and Temporal Lobe Epilepsy: Pathological Association with Altered “Epileptic”γ‐Aminobutyric Acid A Receptors in Dentate Granule Cells

Coulter

2000

Epilepsia

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“…The cellular changes after the injury that lead to the delayed neuronal death are poorly defined. One of the precipitating injuries, SE, stimulates neuronal death lasting for days after the episode as well as the birth of new neurons, axon collateral sprouting, synaptogenesis, and reactive astrocytosis (Babb et al, 1984(Babb et al, , 1991de Lanerolle et al, 1989;Sutula et al, 1989;Houser, 1992Houser, , 1999Houser et al, 1992;Houser and Esclapez, 1996;Fonseca et al, 2002;Garzillo and Mello, 2002). Because reactive astrocytes are associated with many disorders of the nervous system (Miller, 2005), we have become particularly interested in the potential role of astrocytes in delayed responses to injury.…”

Section: Introductionmentioning

confidence: 99%

Enhanced Astrocytic Ca²⁺Signals Contribute to Neuronal Excitotoxicity after Status Epilepticus

Ding¹,

Fellin²,

Zhu³

et al. 2007

J. Neurosci.

244

260

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Status epilepticus (SE), an unremitting seizure, is known to cause a variety of traumatic responses including delayed neuronal death and later cognitive decline. Although excitotoxicity has been implicated in this delayed process, the cellular mechanisms are unclear. Because our previous brain slice studies have shown that chemically induced epileptiform activity can lead to elevated astrocytic Ca 2ϩ signaling and because these signals are able to induce the release of the excitotoxic transmitter glutamate from these glia, we asked whether astrocytes are activated during status epilepticus and whether they contribute to delayed neuronal death in vivo. Using two-photon microscopy in vivo, we show that status epilepticus enhances astrocytic Ca 2ϩ signals for 3 d and that the period of elevated glial Ca 2ϩ signaling is correlated with the period of delayed neuronal death. To ask whether astrocytes contribute to delayed neuronal death, we first administered antagonists which inhibit gliotransmission: MPEP [2-methyl-6-(phenylethynyl)pyridine], a metabotropic glutamate receptor 5 antagonist that blocks astrocytic Ca 2ϩ signals in vivo, and ifenprodil, an NMDA receptor antagonist that reduces the actions of glial-derived glutamate. Administration of these antagonists after SE provided significant neuronal protection raising the potential for a glial contribution to neuronal death. To test this glial hypothesis directly, we loaded Ca 2ϩ chelators selectively into astrocytes after status epilepticus. We demonstrate that the selective attenuation of glial Ca 2ϩ signals leads to neuronal protection. These observations support neurotoxic roles for astrocytic gliotransmission in pathological conditions and identify this process as a novel therapeutic target.

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“…Mild to severe neuronal cell loss might induce synaptic reorganization. 32, 33 The type of extrahippocampal lesions could predict the degree of hippocampal damage. Our analysis supports the 3 types of pathophysiologic mechanisms causing TLE.…”

Section: Discussionmentioning

confidence: 99%

Pathogenic significance of neuronal migration disorders in temporal lobe epilepsy

et al. 2001

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Synaptic reorganization by mossy fibers in human epileptic fascia dentata

Cited by 627 publications

References 47 publications

Mossy Fiber Zinc and Temporal Lobe Epilepsy: Pathological Association with Altered “Epileptic”γ‐Aminobutyric Acid A Receptors in Dentate Granule Cells

Mossy Fiber Zinc and Temporal Lobe Epilepsy: Pathological Association with Altered “Epileptic”γ‐Aminobutyric Acid A Receptors in Dentate Granule Cells

Enhanced Astrocytic Ca²⁺Signals Contribute to Neuronal Excitotoxicity after Status Epilepticus

Pathogenic significance of neuronal migration disorders in temporal lobe epilepsy

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Synaptic reorganization by mossy fibers in human epileptic fascia dentata

Cited by 627 publications

References 47 publications

Mossy Fiber Zinc and Temporal Lobe Epilepsy: Pathological Association with Altered “Epileptic”γ‐Aminobutyric Acid A Receptors in Dentate Granule Cells

Mossy Fiber Zinc and Temporal Lobe Epilepsy: Pathological Association with Altered “Epileptic”γ‐Aminobutyric Acid A Receptors in Dentate Granule Cells

Enhanced Astrocytic Ca2+Signals Contribute to Neuronal Excitotoxicity after Status Epilepticus

Pathogenic significance of neuronal migration disorders in temporal lobe epilepsy

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Enhanced Astrocytic Ca²⁺Signals Contribute to Neuronal Excitotoxicity after Status Epilepticus