scholarly journals AKT isoforms have distinct hippocampal expression and roles in synaptic plasticity

2017 ◽  
Author(s):  
Josien Levenga ◽  
Helen Wong ◽  
Ryan A. Milstead ◽  
Bailey N. Keller ◽  
Lauren E. Laplante ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Synaptic Plasticity ◽  
Brain Function ◽  
Expression Patterns ◽  
Direct Role ◽  
Cellular Processes ◽  
Akt Isoforms ◽  
Hippocampal Synaptic Plasticity ◽  
The Brain ◽  
Unique Expression Pattern

ABSTRACTAKT is a kinase that regulates numerous cellular processes in the brain and mutations in AKT are known to affect brain function. AKT is indirectly implicated in synaptic plasticity, but its direct role has not been studied. Moreover, three highly related AKT isoforms are expressed in the brain, but their individual roles are poorly understood. We find that each AKT isoform has a unique expression pattern in the hippocampus, with AKT1 and AKT3 primarily in neurons but displaying local differences, while AKT2 is in astrocytes. We also find isoform-specific roles for AKT in multiple paradigms of hippocampal synaptic plasticity. AKT1, but not AKT2 or AKT3, is required for L-LTP through regulating activity-induced protein synthesis. Interestingly, AKT activity inhibits mGluR-LTD, with overlapping functions for AKT1 and AKT3. In summary, our studies identify distinct expression patterns and roles in synaptic plasticity for AKT isoforms in the hippocampus.

scholarly journals AKT isoforms have distinct hippocampal expression and roles in synaptic plasticity

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Josien Levenga ◽  
Helen Wong ◽  
Ryan A Milstead ◽  
Bailey N Keller ◽  
Lauren E LaPlante ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Synaptic Plasticity ◽  
Brain Function ◽  
Expression Patterns ◽  
Direct Role ◽  
Cellular Processes ◽  
Akt Isoforms ◽  
Hippocampal Synaptic Plasticity ◽  
The Brain ◽  
Unique Expression Pattern

AKT is a kinase regulating numerous cellular processes in the brain, and mutations in AKT are known to affect brain function. AKT is indirectly implicated in synaptic plasticity, but its direct role has not been studied. Moreover, three highly related AKT isoforms are expressed in the brain, but their individual roles are poorly understood. We find in Mus musculus, each AKT isoform has a unique expression pattern in the hippocampus, with AKT1 and AKT3 primarily in neurons but displaying local differences, while AKT2 is in astrocytes. We also find isoform-specific roles for AKT in multiple paradigms of hippocampal synaptic plasticity in area CA1. AKT1, but not AKT2 or AKT3, is required for L-LTP through regulating activity-induced protein synthesis. Interestingly, AKT activity inhibits mGluR-LTD, with overlapping functions for AKT1 and AKT3. In summary, our studies identify distinct expression patterns and roles in synaptic plasticity for AKT isoforms in the hippocampus.

NMR spectroscopy and imaging of the neonatal brain

2000 ◽  
Vol 28 (2) ◽  
pp. 121-126 ◽  
Author(s):  
C. E. Cooper ◽  
J. S. Wyatt
Keyword(s):  
Blood Flow ◽  
Brain Function ◽  
Blood Oxygenation ◽  
Cell Swelling ◽  
Resonance Spectroscopy ◽  
Neonatal Brain ◽  
Cellular Processes ◽  
Nmr Techniques ◽  
The Brain ◽  
Ischaemic Insult

Magnetic resonance spectroscopy and imaging provide unique information about the brain to the biochemist and the clinician. In particular, the ability to image metabolites other than water and to get detailed information about dynamic cellular processes (such as blood flow, blood oxygenation and cell swelling) is leading to many new insights into brain function and dysfunction. This review describes the use of old and new NMR techniques which demonstrate that mitochondrial dysfunction plays an important role in the cell death that occurs following an hypoxic-ischaemic insult to the neonatal brain.

scholarly journals Selective role of the translin/trax RNase complex in hippocampal synaptic plasticity

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Alan Jung Park ◽  
Mahesh Shivarama Shetty ◽  
Jay M. Baraban ◽  
Ted Abel
Keyword(s):  
Protein Synthesis ◽  
Synaptic Plasticity ◽  
Molecular Mechanisms ◽  
Metabotropic Glutamate Receptor ◽  
Fragile X ◽  
Local Protein Synthesis ◽  
Hippocampal Synaptic Plasticity ◽  
Behavioral Abnormalities ◽  
Local Protein

Abstract Activity-dependent local protein synthesis is critical for synapse-specific, persistent plasticity. Abnormalities in local protein synthesis have been implicated in psychiatric disorders. We have recently identified the translin/trax microRNA-degrading enzyme as a novel mediator of protein synthesis at activated synapses. Additionally, translin knockout (KO) mice, which lack translin/trax, exhibit some of the behavioral abnormalities found in a mouse model of fragile X syndrome (fragile X mental retardation protein-FMRP-KO mice). Therefore, identifying signaling pathways interacting with translin/trax to support persistent synaptic plasticity is a translationally relevant goal. Here, as a first step to achieve this goal, we have assessed the requirement of translin/trax for multiple hippocampal synaptic plasticity paradigms that rely on distinct molecular mechanisms. We found that mice lacking translin/trax exhibited selective impairment in a form of persistent hippocampal plasticity, which requires postsynaptic protein kinase A (PKA) activity. In contrast, enduring forms of plasticity that are dependent on presynaptic PKA were unaffected. Furthermore, these mice did not display exaggerated metabotropic glutamate receptor-mediated long-term synaptic depression (mGluR-LTD), a hallmark of the FMRP KO mice. On the contrary, translin KO mice exhibited deficits in N-methyl-d-aspartate receptor (NMDAR) dependent LTD, a phenotype not observed in the FMRP knockouts. Taken together, these findings demonstrate that translin/trax mediates long-term synaptic plasticity that is dependent on postsynaptic PKA signaling and suggest that translin/trax and FMRP play distinct roles in hippocampal synaptic plasticity.

scholarly journals Selective role of the translin/trax RNase complex in hippocampal synaptic plasticity

2020 ◽  
Author(s):  
Alan Jung Park ◽  
Mahesh Shivarama Shetty ◽  
Jay M. Baraban ◽  
Ted Abel
Keyword(s):  
Protein Synthesis ◽  
Synaptic Plasticity ◽  
Molecular Mechanisms ◽  
Metabotropic Glutamate Receptor ◽  
Fragile X ◽  
Local Protein Synthesis ◽  
Hippocampal Synaptic Plasticity ◽  
Behavioral Abnormalities ◽  
Local Protein

Abstract Activity-dependent local protein synthesis is critical for synapse-specific, persistent plasticity. Abnormalities in local protein synthesis have been implicated in psychiatric disorders. We have recently identified the translin/trax microRNA-degrading enzyme as a novel mediator of protein synthesis at activated synapses. Additionally, translin knockout (KO) mice, which lack translin/trax, exhibit some of the behavioral abnormalities found in a mouse model of fragile X syndrome (fragile X mental retardation protein-FMRP-KO mice). Therefore, identifying signaling pathways interacting with translin/trax to support persistent synaptic plasticity is a translationally relevant goal. Here, as a first step to achieve this goal, we have assessed the requirement of translin/trax for multiple hippocampal synaptic plasticity paradigms that rely on distinct molecular mechanisms. We found that mice lacking translin/trax exhibited selective impairment in a form of persistent hippocampal plasticity, which requires postsynaptic protein kinase A (PKA) activity. In contrast, enduring forms of plasticity that are dependent on presynaptic PKA were unaffected. Furthermore, these mice did not display exaggerated metabotropic glutamate receptor-mediated long-term synaptic depression (mGluR-LTD), a hallmark of the FMRP KO mice. . On the contrary, translin KO mice exhibited deficits in N-methyl-D-aspartate receptor (NMDAR) dependent LTD, a phenotype not observed in the FMRP knockouts. Taken together, these findings demonstrate that translin/trax mediates long-term synaptic plasticity that is dependent on postsynaptic PKA signaling and suggest that translin/trax and FMRP play distinct roles in hippocampal synaptic plasticity.

scholarly journals Effects of calcium on drinking fluorosis-induced hippocampal synaptic plasticity impairment in the offspring of rats

2017 ◽  
Vol 8 (1) ◽  
Author(s):  
Zhang Zigu ◽  
Wang Xiaoyu ◽  
Nian Weiwei ◽  
Liao Qiuxia ◽  
Zhang Rui ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Structural Parameters ◽  
Dietary Calcium ◽  
Structural Parameter ◽  
Brain Functions ◽  
Hippocampal Synaptic Plasticity ◽  
Synapse Density ◽  
Nonsignificant Effect ◽  
The Brain ◽  
Gap Width

AbstractObjectiveThis study investigated the effects of calcium on fluorosis-induced impairment in learning and memory of offspring rats.Results(1) High fluorosis significantly reduced synapse density, length of synaptic active zone, thickness of postsynaptic density, and led to abnormal changes in the structural parameter of synaptic gap width, which was significantly reduced or increased. High dietary calcium significantly reversed the abnormal changes in structural parameters, and low calcium aggravated these variations. (2) Dietary calcium resulted in nonsignificant effect on expression levels of DCX and p38.ConclusionThe results suggested that dietary calcium significantly affected hippocampal synaptic plasticity of offspring of mothers exposed to water fluorosis, but its molecular mechanism may not be related to the expression of DCX and p38 in the brain. The findings also demonstrate the important effects of maternal exposure to water fluorosis on offspring brain functions before water improvement.

Regulation of Protein Synthesis by eIF4E in the Brain

2020 ◽  
Author(s):  
Kleanthi Chalkiadaki ◽  
Stella Kouloulia ◽  
Clive R. Bramham ◽  
Christos G. Gkogkas
Keyword(s):  
Protein Synthesis ◽  
Brain Function ◽  
Regulation Of Gene Expression ◽  
Mrna Translation ◽  
Rate Limiting Step ◽  
Limiting Step ◽  
Eukaryotic Mrnas ◽  
Rate Limiting ◽  
The Brain ◽  
Key Pathways

Regulation of gene expression at the level of mRNA translation is crucial for all the functions our brains carry out. eIF4E binds to the 5′-end of eukaryotic mRNAs and dictates the rate-limiting step of cap-dependent initiation. This chapter reviews the key pathways regulating eIF4E function, but also the less studied and novel mechanisms of eIF4E modulation, linked to synaptic plasticity, learning and memory, and nervous system disorders. Understanding how regulation of protein synthesis by eIF4E affects different aspects of brain function is yet elusive.

Astrocytes and Brain Function: Implications for Reproduction

2003 ◽  
Vol 228 (3) ◽  
pp. 253-260 ◽  
Author(s):  
Krishnan M. Dhandapani ◽  
Virendra B. Mahesh ◽  
Darrell W. Brann
Keyword(s):  
Synaptic Plasticity ◽  
Brain Function ◽  
Potential Role ◽  
Potential Contribution ◽  
Neuroendocrine Function ◽  
Gnrh Neurons ◽  
Gnrh Release ◽  
17Β Estradiol ◽  
Luteinizing Hormone Surge ◽  
The Brain

Recent evidence suggests that astrocytes have important neuroregulatory functions in addition to their classic functions of support and segregation of neurons. These newly revealed functions include regulation of neuron communication, neurosecretion, and synaptic plasticity. Although these actions occur throughout the brain, this review will focus on astrocyteneuron interactions in the hypothalamus, particularly with respect to their potential contribution to the regulation of gonadotropin-releasing hormone (GnRH) secretion and reproduction. Hypothalamic astrocytes have been documented to release a variety of neuroactive factors, including transforming growth factors-α and -β, insulin-like growth factor-1, prostaglandin E2, and the neurosteroid, 3α-hydroxy-5α-pregnane-20-one. Each of these factors has been shown to stimulate GnRH release, and receptors for each factor have been documented on GnRH neurons. Astrocytes have also been implicated in the regulation of synaptic plasticity in key areas of the hypothalamus that control GnRH release, an effect achieved by extension and retraction of glial processes (i.e., glial ensheathment). Through this mechanism, the number of synapses on GnRH neurons and GnRH regulatory neurons can potentially be modulated, thereby influencing the activation state of GnRH neurons. The steroid hormone 17β-estradiol, which triggers the GnRH and luteinizing hormone surge, has been shown to induce the astrocyte-regulated changes in hypothalamic synaptic plasticity, as well as enhance formation and release of the astrocyte neuroactive factors, thereby providing another potential mechanistic layer for astrocyte regulation of GnRH release. As a whole, these studies provide new insights into the diversity of astrocytes and their potential role in reproductive neuroendocrine function.

scholarly journals Selective role of the translin/trax RNase complex in hippocampal synaptic plasticity

2020 ◽  
Author(s):  
Alan Jung Park ◽  
Mahesh Shivarama Shetty ◽  
Jay M. Baraban ◽  
Ted Abel
Keyword(s):  
Protein Synthesis ◽  
Synaptic Plasticity ◽  
Mouse Model ◽  
Fragile X Syndrome ◽  
Metabotropic Glutamate Receptor ◽  
Fragile X ◽  
Local Protein Synthesis ◽  
Hippocampal Synaptic Plasticity ◽  
Local Protein

Abstract Activity-dependent local protein synthesis is critical for synapse-specific, persistent plasticity. Abnormalities in local protein synthesis have been implicated in psychiatric disorders. We have recently identified the translin/trax microRNA-degrading enzyme as a novel mediator of protein synthesis at activated synapses. Additionally, mice lacking translin/trax exhibit some of the behavioral abnormalities found in a mouse model of fragile X syndrome. Therefore, identifying signaling pathways interacting with translin/trax to support persistent synaptic plasticity is a translationally relevant goal. Here, as a first step to achieve this goal, we have assessed the requirement of translin/trax for multiple hippocampal synaptic plasticity paradigms that rely on distinct molecular mechanisms. We found that mice lacking translin/trax exhibited selective impairment in a form of persistent hippocampal plasticity, which requires postsynaptic PKA activity. In contrast, enduring forms of plasticity that are dependent on presynaptic PKA were unaffected. Furthermore, these mice did not display exaggerated metabotropic glutamate receptor-mediated long-term synaptic depression, a hallmark of the mouse model of fragile X syndrome. Taken together, these findings demonstrate that translin/trax mediates long-term synaptic plasticity that is dependent on postsynaptic PKA signaling.

scholarly journals Selective role of the translin/trax RNase complex in hippocampal synaptic plasticity

2020 ◽  
Author(s):  
Alan Jung Park ◽  
Mahesh Shivarama Shetty ◽  
Jay M. Baraban ◽  
Ted Abel
Keyword(s):  
Protein Synthesis ◽  
Synaptic Plasticity ◽  
Mouse Model ◽  
Fragile X Syndrome ◽  
Metabotropic Glutamate Receptor ◽  
Fragile X ◽  
Local Protein Synthesis ◽  
Hippocampal Synaptic Plasticity ◽  
Local Protein

AbstractActivity-dependent local protein synthesis is critical for synapse-specific, persistent plasticity. Abnormalities in local protein synthesis have been implicated in psychiatric disorders. We have recently identified the translin/trax microRNA-degrading enzyme as a novel mediator of protein synthesis at activated synapses. Additionally, mice lacking translin/trax exhibit some of the behavioral abnormalities found in a mouse model of fragile X syndrome. Therefore, identifying signaling pathways interacting with translin/trax to support persistent synaptic plasticity is a translationally relevant goal. Here, as a first step to achieve this goal, we have assessed the requirement of translin/trax for multiple hippocampal synaptic plasticity paradigms that rely on distinct molecular mechanisms. We found that mice lacking translin/trax exhibited selective impairment in a form of persistent hippocampal plasticity, which requires postsynaptic PKA activity. In contrast, enduring forms of plasticity that are dependent on presynaptic PKA were unaffected. Furthermore, these mice did not display exaggerated metabotropic glutamate receptor-mediated long-term synaptic depression, a hallmark of the mouse model of fragile X syndrome. Taken together, these findings demonstrate that translin/trax mediates long-term synaptic plasticity that is dependent on postsynaptic PKA signaling.

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