Transforming growth factor alpha attenuates the functional expression of AMPA receptors in cortical GABAergic neurons

Namba, Hisaaki; Nagano, Tadasato; Iwakura, Yuriko; Xiong, Huabao; Jourdi, Hussam; Takei, Nobuyuki; Nawa, Hiroyuki

doi:10.1016/j.mcn.2005.12.002

Cited by 28 publications

(22 citation statements)

References 69 publications

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“…These neurotrophic factors positively or negatively regulate postnatal phenotypic differentiation and synaptic maturation in this neuronal population (Nawa and Takei, 2001; Nagano et al, 2003Nagano et al, , 2007Namba et al, 2006). Our findings suggest that these factors alter the sensitivity and expression of AMPA receptors in neocortical GABAergic neurons during postnatal development, although the specific synaptic effects depend on species of neurotrophic factor.…”

Section: Introductionmentioning

confidence: 68%

Neuregulin-1 Signals from the Periphery Regulate AMPA Receptor Sensitivity and Expression in GABAergic Interneurons in Developing Neocortex

Abe¹,

Namba²,

Kato³

et al. 2011

J. Neurosci.

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Neuregulin-1 (NRG1) signaling is thought to contribute to both neuronal development and schizophrenia neuropathology. Here, we describe the developmental effects of excessive peripheral NRG1 signals on synaptic activity and AMPA receptor expression of GABAergic interneurons in postnatal rodent neocortex. A core peptide common to all NRG1 variants (eNRG1) was subcutaneously administered to mouse pups. Injected eNRG1 penetrated the blood-brain barrier and activated ErbB4 NRG1 receptors in the neocortex, in which ErbB4 mRNA is predominantly expressed by parvalbumin-positive GABAergic interneurons. We prepared neocortical slices from juvenile mice that were receiving eNRG1 subchronically and recorded inhibitory synaptic activity from layer V pyramidal neurons. Postnatal eNRG1 treatment significantly enhanced polysynaptic IPSCs, although monosynaptic IPSCs were not affected. Examination of excitatory inputs to parvalbumin-containing GABAergic interneurons revealed that eNRG1 treatment significantly increased AMPA-triggered inward currents and the amplitudes and frequencies of miniature EPSCs (mEPSCs). Similar effects on mEPSCs were observed in mice treated with a soluble, full-length form of NRG1 type I. Consistent with the electrophysiologic data, expression of the AMPA receptor GluA1 (i.e., GluR1, GluRA) was upregulated in the postsynaptic density/cytoskeletal fraction prepared from eNRG1-treated mouse neocortices. Cortical GABAergic neurons cultured with eNRG1 exhibited a significant increase in surface GluA1 immunoreactivity at putative synaptic sites on their dendrites. These results indicate that NRG1 circulating in the periphery influences postnatal development of synaptic AMPA receptor expression in cortical GABAergic interneurons and may play a role in conditions characterized by GABA-associated neuropathologic processes.

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Section: Introductionmentioning

confidence: 68%

Neuregulin-1 Signals from the Periphery Regulate AMPA Receptor Sensitivity and Expression in GABAergic Interneurons in Developing Neocortex

Abe¹,

Namba²,

Kato³

et al. 2011

J. Neurosci.

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“…Further quantitative assessment of mRNA levels was carried out with a real time PCR machine (Light Cycler, Roche Diagnostics) (27). Total RNA (100 ng) was subjected to RT-PCR amplification (60°C for 10 min, 94°C for 2 s, 30 cycles of 94°C; 60°C for 15 s for eEF2, and 60°C for 10 min, 94°C for 2 s; 30 cycles of 94°C, 55°C for 5 s, and 72°C for 10 s for ␤-actin) in a final volume of 25 l using RT-PCR high plus (Toyobo, Osaka, Japan), containing of 1/20,000 SYBR Green I (Molecular Probes) and 5 pmol of primers.…”

Section: Methodsmentioning

confidence: 99%

Brain-derived Neurotrophic Factor Enhances the Basal Rate of Protein Synthesis by Increasing Active Eukaryotic Elongation Factor 2 Levels and Promoting Translation Elongation in Cortical Neurons

Takei

Kawamura

Ishizuka

et al. 2009

Journal of Biological Chemistry

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The constitutive and activity-dependent components of protein synthesis are both critical for neural function. Although the mechanisms controlling extracellularly induced protein synthesis are becoming clear, less is understood about the molecular networks that regulate the basal translation rate. Here we describe the effects of chronic treatment with various neurotrophic factors and cytokines on the basal rate of protein synthesis in primary cortical neurons. Among the examined factors, brain-derived neurotrophic factor (BDNF) showed the strongest effect. The rate of protein synthesis increased in the cortical tissues of BDNF transgenic mice, whereas it decreased in BDNF knock-out mice. BDNF specifically increased the level of the active, unphosphorylated form of eukaryotic elongation factor 2 (eEF2). The levels of active eEF2 increased and decreased in BDNF transgenic and BDNF knock-out mice, respectively. BDNF decreased kinase activity and increased phosphatase activity against eEF2 in vitro. Additionally, BDNF shortened the ribosomal transit time, an index of translation elongation. In agreement with these results, overexpression of eEF2 enhanced protein synthesis. Taken together, our results demonstrate that the increased level of active eEF2 induced by chronic BDNF stimulation enhances translational elongation processes and increases the total rate of protein synthesis in neurons.The synthesis and post-translational modification of proteins play key roles in neural development, synaptic plasticity, and cognitive brain functions such as learning and memory (1, 2). Recent studies have revealed that activity-dependent regulation of translation affects neural plasticity (3, 4). Previously, we reported that BDNF, 2 a critical molecule for neural plasticity (5-7), enhances protein synthesis and activates the translational machinery in central nervous system neurons (8). In addition, neurotransmitters such as glutamate (9, 10), dopamine (11), and serotonin (12) are also reported to facilitate translation in neurons. These observations indicate that endogenous molecules can acutely modulate neuronal translation in response to neural activity. Translation of an mRNA molecule comprises three steps: initiation, elongation, and release (or termination) (13). In the first step, mRNA and methionyltRNA i Met are recruited to a ribosome. During elongation, aminoacyl-tRNAs are sequentially recruited and the nascent peptide chain lengthens incrementally as amino acids are covalently attached via peptide bonds. Finally, the polypeptide chain is released from the ribosome. Each step is regulated by a variety of factors. The activities of these regulatory proteins are predominantly controlled by phosphorylation and GTP binding. BDNF activates both initiation and elongation by modulating these processes (8,14,15).In addition to these acute, stimulation-induced changes in the translation rate, the long term regulation of translation plays important roles in developing and mature brains. In fact, recent studies have shown that ge...

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“…GABA, a major inhibitory neurotransmitter in the CNS, is synthesized from glutamate, a principal excitatory neurotransmitter, through a GABA shunt. In contrast to its neurotrophic action on dopaminergic neurons, EGFR activation negatively regulates GABAergic neurons' function by attenuating the activity of glutamate receptor channels (2,380,384). EGFR is also expressed in neurons located at the subparaventricular zone (SPZ) of the hypothalamus, the major target field of the suprachiasmatic nucleus (SCN), site of the circadian clock.…”

Section: A Egfr Expression and Physiological Function In The Cnsmentioning

confidence: 99%

Expression and Function of the Epidermal Growth Factor Receptor in Physiology and Disease

Chen

Zeng

Forrester

et al. 2016

Physiological Reviews

219

156

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The epidermal growth factor receptor (EGFR) is the prototypical member of a family of membrane-associated intrinsic tyrosine kinase receptors, the ErbB family. EGFR is activated by multiple ligands, including EGF, transforming growth factor (TGF)-α, HB-EGF, betacellulin, amphiregulin, epiregulin, and epigen. EGFR is expressed in multiple organs and plays important roles in proliferation, survival, and differentiation in both development and normal physiology, as well as in pathophysiological conditions. In addition, EGFR transactivation underlies some important biologic consequences in response to many G protein-coupled receptor (GPCR) agonists. Aberrant EGFR activation is a significant factor in development and progression of multiple cancers, which has led to development of mechanism-based therapies with specific receptor antibodies and tyrosine kinase inhibitors. This review highlights the current knowledge about mechanisms and roles of EGFR in physiology and disease.

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Transforming growth factor alpha attenuates the functional expression of AMPA receptors in cortical GABAergic neurons

Cited by 28 publications

References 69 publications

Neuregulin-1 Signals from the Periphery Regulate AMPA Receptor Sensitivity and Expression in GABAergic Interneurons in Developing Neocortex

Neuregulin-1 Signals from the Periphery Regulate AMPA Receptor Sensitivity and Expression in GABAergic Interneurons in Developing Neocortex

Brain-derived Neurotrophic Factor Enhances the Basal Rate of Protein Synthesis by Increasing Active Eukaryotic Elongation Factor 2 Levels and Promoting Translation Elongation in Cortical Neurons

Expression and Function of the Epidermal Growth Factor Receptor in Physiology and Disease

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