Kainate-induced epilepsy alters protein expression of AMPA receptor subunits GluR1, GluR2 and AMPA receptor binding protein in the rat hippocampus

Sommer, Clemens; Roth, S.; Kiessling, Marika

doi:10.1007/s004010000310

Cited by 34 publications

(19 citation statements)

References 61 publications

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“…A non-NMDA receptor blocker, CNQX (6-cyano-7-nitroquinoxaline-2,3-dione), suppresses KA-induced neuron loss in the CA3 region (Lee et al, 2002), showing that neuronal damage is caused by activation of KA receptors. KA also regulates calcium-permeable GluR2 levels prior to neuronal death (Grooms et al, 2000;Sommer et al, 2001). These findings indicate a direct effect of KA on CA3 neurons via AMPA/KA receptors.…”

Section: Discussionmentioning

confidence: 78%

Endothelial microsomal prostaglandin E synthase‐1 exacerbates neuronal loss induced by kainate

Takemiya

Matsumura

Sugiura

et al. 2009

J of Neuroscience Research

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Prostaglandin E(2) (PGE(2)) is increased in the brain after kainic acid (KA) treatment. We previously demonstrated that KA also induces PG synthase cyclooxygenase-2 (COX-2) expression rapidly in neurons of the brain and slowly in astrocytes and endothelia. Prevention of KA-induced neuronal damage by nonneuronal COX-2 inhibition suggests a novel modulatory mechanism for neuronal injury by nonneuronal PGs. It remains unclear, however, which PG synthase is responsible for this modulation following COX-2 synthesis after neuronal insult. In addition, the PG receptor subtype that is involved in neuronal loss remains controversial. Here we demonstrate that microinjection of KA induces microsomal prostaglandin E synthase-1 (mPGES-1) in venous endothelial cells but not in neurons or astrocytes. We found that mPGES-1 plays a central role in delayed production of PGE(2) and that mPGES-1-deficient mice exhibit significantly less neuronal loss induced by KA. Furthermore, KA injection caused an increase in the immunoreactivity for the EP3 receptor in the astrocytic endfeet that surround vascular endothelia. Neurons form intimate interactions with astrocytes via glutamate, and astrocytes contact vascular endothelia through endfeet. These findings suggest that endothelial cells may control neuronal excitotoxicity, most likely by regulating astrocytes via inducible PGE(2).

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Section: Discussionmentioning

confidence: 78%

Endothelial microsomal prostaglandin E synthase‐1 exacerbates neuronal loss induced by kainate

Takemiya

Matsumura

Sugiura

et al. 2009

J of Neuroscience Research

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“…For semi-quantitative analysis of in situ hybridization results optical densitometry was performed as previously described (59). All sections were examined at a final magnification of ϫ40 with a Zeiss Axiophot microscope (Jena, Germany).…”

Section: Methodsmentioning

confidence: 99%

Expression of Synaptopodin, an Actin‐associated Protein, in the Rat Hippocampus after Limbic Epilepsy

et al. 2001

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Synaptopodin, a 100 kD protein, associated with the actin cytoskeleton of the postsynaptic density and dendritic spines, is thought to play a role in modulating actin-based shape and motility of dendritic spines during formation or elimination of synaptic contacts. Temporal lobe epilepsy in humans and in rats shows neuronal damage, aberrant sprouting of hippocampal mossy fibers and subsequent synaptic remodeling processes. Using kainic acid (KA) induced epilepsy in rats, the postictal hippocampal expression of synaptopodin was analyzed by in situ hybridization (ISH) and immunohistochemistry. Sprouting of mossy fibers was visualized by a modified Timm's staining. ISH showed elevated levels of Synaptopodin mRNA in perikarya of CA3 principal neurons, dentate granule cells and in surviving hilar neurons these levels persisted up to 8 weeks after seizure induction. Synaptopodin immunoreactivity in the dendritic layers of CA3, in the hilus and in the inner molecular layer of the dentate gyrus (DG) was initially reduced. Eight weeks after KA treatment Synaptopodin protein expression returned to control levels in dendritic layers of CA3 and in the entire molecular layer of the DG. The recovery of protein expression was accompanied by simultaneous supra-and infragranular mossy fiber sprouting. Postictal upregulation of Synaptopodin mRNA levels in target cell populations of limbic epilepsy-elicited damage and subsequent Synaptopodin protein expression largely co-localized with remodeling processes as demonstrated by mossy fiber sprouting. It may thus represent a novel postsynaptic molecular correlate of hippocampal neuroplasticity.

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“…[30] Interestingly, GluR2 is also related to the aforementioned diseases. [34][35][36] It has been reported that GABA upregulates the expression of GluR2 in the mouse brain. [37] In the present study, GluR2 expression was also increased in both GABA-treated SH-SY5Y cells and GABAtreated mice.…”

Section: Discussionmentioning

confidence: 99%

“…Glutamate receptor 2 (GluR2, also known as GluR-B or GluA2), a subunit of the α-amino-3-hydroxy-5-methyl-4-isoxazole propionate(AMPA) receptor, plays an important role in the pathogenesis of some neurological diseases. [33][34][35][36] It has been reported that GluR2 is regulated by GABA; however, the specific mechanism by which GABA regulates GluR2 has not been identified. [37] Graff et al found that the expression of GluR2 increased when HDAC2 was inhibited.…”

Section: Introductionmentioning

confidence: 99%

As a Histone Deacetylase Inhibitor, γ‐Aminobutyric Acid Upregulates GluR2 Expression: An In Vitro and In Vivo Study

Xing

Jiang

et al. 2019

Molecular Nutrition Food Res

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Scope γ‐Aminobutyric acid (GABA) possesses extensive physiological functions and can be directly obtained from foods. GABA‐enriched functional foods have been developed and the commercial demands for GABA are increasing. GABA is widely recognized as a central nervous system inhibitory neurotransmitter and plays an important role in some diseases by binding to its receptors. However, some of the functions of GABA are not explained by neurotransmission or GABA receptor pathways. Therefore, this study investigates whether GABA has the potential to inhibit histone deacetylase (HDAC). Methods and results It is found that GABA inhibits HDAC1/2/3 expression and upregulates histone acetylation levels (Ace‐H3K9/Ace‐H4K12) in SH‐SY5Y cells (which express GABA receptors), 3T3‐L1 cells (which do not express GABA receptors), and the cerebral cortex in mice. Glutamate receptor 2 (GluR2) is a subunit of the α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionate (AMPA) receptor and is implicated in the pathogenesis of some neurological diseases. It is also found that GABA increases GluR2 expression by inhibiting HDAC1/2 but not HDAC3. Conclusion A novel role for GABA is demonstrated in which it acts as an HDAC inhibitor. The present study expands the horizons for exploring the non‐neurotransmitter functions of GABA.

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Kainate-induced epilepsy alters protein expression of AMPA receptor subunits GluR1, GluR2 and AMPA receptor binding protein in the rat hippocampus

Cited by 34 publications

References 61 publications

Endothelial microsomal prostaglandin E synthase‐1 exacerbates neuronal loss induced by kainate

Endothelial microsomal prostaglandin E synthase‐1 exacerbates neuronal loss induced by kainate

Expression of Synaptopodin, an Actin‐associated Protein, in the Rat Hippocampus after Limbic Epilepsy

As a Histone Deacetylase Inhibitor, γ‐Aminobutyric Acid Upregulates GluR2 Expression: An In Vitro and In Vivo Study

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