Alterations of the GluR-B AMPA receptor subunit flip/flop expression in kainate-induced epilepsy and ischemia

Pollard, H.; Héron, Anne; Moreau, J.; Ben‐Ari, Yehezkel; Khrestchatisky, Michel

doi:10.1016/0306-4522(93)90004-y

Cited by 188 publications

(109 citation statements)

References 42 publications

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“…In rat hippocampus, a significant upregulation of GIuR-A flip and GluR-B flip mRNA was observed after kindling [4]. A similar transient elevation of GluR-B flip was reported in hippocampus of rats with kainate-induced epilepsy [5].…”

Section: Introductionsupporting

confidence: 74%

Alternative splicing of AMPA receptor subunits: regulation in clonal cell lines

Christnacher¹,

Sommer²

1995

FEBS Letters

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Section: Introductionsupporting

confidence: 74%

Alternative splicing of AMPA receptor subunits: regulation in clonal cell lines

Christnacher¹,

Sommer²

1995

FEBS Letters

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“…Changes in the flip/flop ratio for GluRs in the hippocampus have been demonstrated in various seizure models (Kamphuis et al 1994;Lason et al 1997Lason et al , 1998Pollard et al 1993), including a neurodevelopmental model (Rafiki et al 1998). Most relevant to the present study, 2 weeks of haloperidol treatment increased the flip/flop ratio for GluR2 in the rat hippocampus and dorsolateral striatum, while 16 weeks of haloperidol increased the ratio in the striatum and frontoparietal cortex (Eastwood et al 1994).…”

Section: Many Lines Of Evidence Implicate Dysfunctional Excitatory Ammentioning

confidence: 54%

“…AMPA receptors containing flop isoforms of the GluR1-4 subunits exhibit a faster rate of desensitization than receptors containing flip isoforms (Lambolez et al 1996;Mosbacher et al 1994;Sommer et al 1990). Increased incorporation of flip variants into synaptic AMPA receptors might enable synapses to switch from low gain to high gain .Changes in the flip/flop ratio for GluRs in the hippocampus have been demonstrated in various seizure models (Kamphuis et al 1994;Lason et al 1997Lason et al , 1998Pollard et al 1993), including a neurodevelopmental model (Rafiki et al 1998). Most relevant to the present study, 2 weeks of haloperidol treatment increased the flip/flop ratio for GluR2 in the rat hippocampus and dorsolateral striatum, while 16 weeks of haloperidol increased the ratio in the striatum and frontoparietal cortex (Eastwood et al 1994).…”

mentioning

confidence: 99%

Expression of AMPA Receptor Flip and Flop mRNAs in the Nucleus Accumbens and Prefrontal Cortex after Neonatal Ventral Hippocampal Lesions

Stine

Wolf

2001

Neuropsychopharmacology

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Many lines of evidence implicate dysfunctional excitatory amino acid (EAA) transmission in schizophrenia. The present study examined ␣ -amino-3-hydroxy-5-methylisoxazole-4-priopionate (AMPA) receptor expression in the prefrontal cortex (PFC) and nucleus accumbens (NAc) using a rat model of schizophrenia in which excitotoxic lesions of ventral hippocampus (VH) on postnatal day (PD) 7 lead to the postpubertal emergence of behavioral abnormalities that resemble schizophrenic symptoms. In situ hybridization histochemistry with 35 S-labeled oligonucleotide probes was used to quantify mRNA levels for respectively Recent hypotheses about the pathophysiology of schizophrenia have posited defects in excitatory amino acid (EAA) transmission (e.g., Carlsson and Carlsson 1990; Coyle 1996;Krystal et al. 1999;Olney and Farber 1995). A number of different lines of evidence support the involvement of EAAs. First, N-methyl-D-aspartate (NMDA) receptor antagonists produce effects in normal human subjects that resemble those associated with schizophrenia (Krystal et al. 1999). Second, schizophrenic brains exhibit abnormalities in glutamate metabolism (Bartha et al. 1997; Do et al. 1995; Faustman et al. 1999;Tsai et al. 1995) and glutamate receptor expression (reviewed by Meador-Woodruff and Healy 2000). Finally, drugs that alter glutamate transmission can ameliorate schizophrenic symptoms (Heresco-Levy et al. 1996;Javitt et al. 1994;Tsai et al. 1998 NO . 3 antipsychotic drug treatment alters EAA levels in the CSF and serum of schizophrenic patients (Evins et al. 1997;Labarca et al. 1995).Preclinical research also supports a role for EAAs in the pathogenesis of schizophrenia. When tested in rats, NMDA receptor antagonists produce behavioral responses that model schizophrenic symptoms and are blocked by antipsychotic drugs, including clozapine (e.g., Hauber 1993). Chronic administration of antipsychotic drugs alters glutamate receptor expression in rat brain (Chen et al. 1998; Eastwood et al. 1994 Eastwood et al. , 1996 Fitzgerald et al. 1995;Healy and Meador-Woodruff 1997;Riva et al. 1997;Tascedda et al. 1999) and alters EAA levels as measured by microdialysis (Daly and Moghaddam 1993;See and Chapman 1994;See and Lynch 1996;Yamamoto and Cooperman 1994).The ␣ -amino-3-hydroxy-5-methylisoxazole-4-priopionate (AMPA) subtype of glutamate receptor mediates the majority of excitatory transmission in brain. Different combinations of four AMPA receptor subunits (GluR1-4) give rise to heteromeric receptors with distinct properties (Hollman and Heinemann, 1994). The purpose of the present study was to examine the possible role of alterations in AMPA receptor expression in schizophrenia, using a rat model for schizophrenia in which excitotoxic lesions of ventral hippocampus (VH) are produced on postnatal day (PD) 7 . By interrupting connections between the limbic system and cortex during the vulnerable neonatal period, neonatal VH lesions may produce developmental changes related to those that are believed to underlie schizophre...

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“…Forebrain ischemia suppresses GluR2 mRNA and protein expression in CA1 neurons (7)(8)(9)(10) and enhances AM-PAR-mediated Ca 2ϩ influx into CA1 neurons before death (11). Ischemia induces prolonged, Ca 2ϩ -dependent AMPA excitatory postsynaptic currents at CA1 synapses, which are sensitive to Joro spider toxin and 1-naphthyl acetyl spermine, channel blockers selective for Ca 2ϩ -permeable AMPARs (12)(13)(14).…”

mentioning

confidence: 99%

Hypothermia rescues hippocampal CA1 neurons and attenuates down-regulation of the AMPA receptor GluR2 subunit after forebrain ischemia

Colbourne

Grooms

Zukin

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

103

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Brief forebrain ischemia in rodents induces selective and delayed neuronal death, particularly of hippocampal CA1 pyramidal neurons. Neuronal death is preceded by down-regulation specific to CA1 of GluR2, the ␣-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunit that limits Ca 2؉ influx. This alteration is hypothesized to cause neurodegeneration by permitting a lethal influx of Ca 2؉ and͞or Zn 2؉ through newly formed GluR2-lacking AMPA receptors. Two days of mild hypothermia induced 1 h after ischemia potently and lastingly protects against ischemic injury. We examined molecular mechanisms underlying hypothermia-induced neuroprotection. We report that hypothermia rescues most hippocampal CA1 neurons from ischemia-induced cell death and attenuates ischemia-induced down-regulation of mRNA encoding the AMPA receptor subunit GluR2. Ischemia induced a marked down-regulation of GluR2 mRNA and a small down-regulation of GluR1 mRNA in CA1 at 2 days, as assessed by quantitative in situ hybridization. The ischemia-induced changes in gene expression were cell-specific in that GluR2 was not significantly altered in CA3 or dentate gyrus. After ischemia treated by hypothermia GluR2 mRNA expression was modestly reduced at 2 days and exhibited complete recovery to control levels at 7 days. Hypothermia prevented ischemia induced changes in GluR1 mRNA expression. These findings suggest that intervention at the level of transcriptional regulation of the GluR2 gene may be a mechanism by which prolonged postischemic cooling rescues CA1 neurons otherwise ''destined to die.'' cerebral ischemia ͉ neuroprotection ͉ GluR1 ͉ global ischemia ͉ hippocampus

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Alterations of the GluR-B AMPA receptor subunit flip/flop expression in kainate-induced epilepsy and ischemia

Cited by 188 publications

References 42 publications

Alternative splicing of AMPA receptor subunits: regulation in clonal cell lines

Alternative splicing of AMPA receptor subunits: regulation in clonal cell lines

Expression of AMPA Receptor Flip and Flop mRNAs in the Nucleus Accumbens and Prefrontal Cortex after Neonatal Ventral Hippocampal Lesions

Hypothermia rescues hippocampal CA1 neurons and attenuates down-regulation of the AMPA receptor GluR2 subunit after forebrain ischemia

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