Astrocyte-mediated metaplasticity in the hippocampus: Help or hindrance?

Jones, Owen D.

doi:10.1016/j.neuroscience.2015.08.035

Cited by 26 publications

(15 citation statements)

References 153 publications

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“…Conversely, the significant decrease in hypothermia PDT LD 50 in normal astrocytes is of concern. Reactive astrogliosis following neuronal insults could be beneficial or a hindrance to long-term neuronal survival, as reactive gliosis can both contain or lead to neuronal tissue cell death in an area larger than initially injured[ 32 ].…”

Section: Discussionmentioning

confidence: 99%

ALA-PpIX mediated photodynamic therapy of malignant gliomas augmented by hypothermia

et al. 2017

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BackgroundMalignant gliomas are highly invasive, difficult to treat, and account for 2% of cancer deaths worldwide. Glioblastoma Multiforme (GBM) comprises the most common and aggressive intracranial tumor. The study hypothesis is to investigate the modification of Photodynamic Therapy (PDT) efficacy by mild hypothermia leads to increased glioma cell kill while protecting normal neuronal structures.MethodsPhotosensitizer accumulation and PDT efficacy in vitro were quantified in various glioma cell lines, primary rat neurons, and astrocytes. In vivo studies were carried out in healthy brain and RG2 glioma of naïve Fischer rats. Hypothermia was induced at 1 hour pre- to 2 hours post-PDT, with ALA-PpIX accumulation and PDT treatments effects on tumor and normal brain PDT quantified using optical spectroscopy, histology, immunohistochemistry, MRI, and survival studies, respectively.FindingsIn vitro studies demonstrated significantly improved post-PDT survival in primary rat neuronal cells. Rat in vivo studies confirmed a neuroprotective effect to hypothermia following PpIX mediated PDT by T2 mapping at day 10, reflecting edema/inflammation volume reduction. Mild hypothermia increased PpIX fluorescence in tumors five-fold, and the median post-PDT rat survival time (8.5 days normothermia; 14 days hypothermia). Histology and immunohistochemistry show close to complete cellular protection in normal brain structures under hypothermia.ConclusionsThe benefits of hypothermia on both normal neuronal tissue as well as increased PpIX fluorescence and RG2 induced rat survival strongly suggest a role for hypothermia in photonics-based surgical techniques, and that a hypothermic intervention could lead to considerable patient outcome improvements.

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Section: Discussionmentioning

confidence: 99%

ALA-PpIX mediated photodynamic therapy of malignant gliomas augmented by hypothermia

et al. 2017

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“…Taking into consideration that S100B suppresses LTP [45], we suggest that the increase in S100B expression is a part of the mechanism of synaptic scaling, a goal of which is to keep synaptic connection strengths within an optimal range necessary for proper functioning of a neuronal network. Heterodendritic metaplasticity [82] can be one of the manifestations of this mechanism. In the area CA1 of the hippocampus, priming stimulation delivered to inputs to the basal dendrites of pyramidal cells generates metaplastic inhibition of LTP and facilitates long-term depression (LTD) at inputs to the apical dendrites, hundreds of microns away and on the other side of the soma.…”

Section: Resultsmentioning

confidence: 99%

Long-Term Potentiation-Associated Gene Expression: Involvement of the Tumour Protein p53

Lisachev¹,

Штарк²

2018

The Hippocampus - Plasticity and Functions

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Long-term potentiation of synaptic transmission (LTP) is one of the most studied manifestations of neuroplasticity and hippocampus is a classic object for the study of LTP mechanisms. The early phase of LTP depends on modifications of pre-existing synaptic proteins and the late phase of LTP needs de novo protein synthesis and gene expression. LTP-associated dynamics of the transcriptome and mechanisms of coupling synaptic activity with gene expression are intensively studied, but due to the vast complexity of the issue, abundance of unresolved questions remains in this field. The diversity of brain cell types is one of the main challenges. Until relatively recently, the analysis of molecular and genetic aspects of neuroplasticity has usually been confined to neuronal populations. Meanwhile, glia substantially contributes to synaptic transmission regulation. Astrocytes release various gliotransmitters, which modulate synaptic transmission and plasticity. S100B is one of those glia-derived regulatory factors. Learning in rats is accompanied by an increase in S100B expression in various brain regions including the hippocampus. The present study is focused on the neuroplasticity-associated S100B expression upregulation using long-term post-tetanic potentiation in rat hippocampal slices. In this chapter, we present a short review of published articles devoted to the analysis of gene expression during LTP formation including studies of the mechanism of LTP-associated S100B upregulation in hippocampus.

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“…Neurotrophic factors and central monoamines are associated with alterations in hippocampal progenitor proliferation and cell survival, an effect which is reversed by antidepressants via stimulation of neurotrophic factors, including BDNF, which regulates synaptic protein synthesis, and by modulation of glial cells, causing an increase in dendritic arborization and synaptogenesis 81 . Astrocytes are potent regulators of synaptic plasticity, and astrocyte-mediated metaplasticity mechanisms may be engaged by pathological signaling in the hippocampus 83 . Small packets of glutamate are released by astrocytes, acting on extrasynaptic glutamate NMDA receptor subtype 2B 84 - 87 .…”

Section: Discussionmentioning

confidence: 99%

“…Small packets of glutamate are released by astrocytes, acting on extrasynaptic glutamate NMDA receptor subtype 2B 84 - 87 . Activation of a single astrocyte in the CA1 triggers synchronous slow inward currents in numerous adjacent neurons, suggesting that astrocytes play a role in coordination of neural synchrony 83 , 86 . Taken together, we postulate that MSC-EAATs that migrated to the hippocampus integrated in this region and became part of the tissue machinery, thus increasing hippocampal EAAT and BDNF levels.…”

Section: Discussionmentioning

confidence: 99%

Therapeutic Effect of Astroglia-like Mesenchymal Stem Cells Expressing Glutamate Transporter in a Genetic Rat Model of Depression

et al. 2017

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Recent studies have proposed that abnormal glutamatergic neurotransmission and glial pathology play an important role in the etiology and manifestation of depression. It was postulated that restoration of normal glutamatergic transmission, by enhancing glutamate uptake, may have a beneficial effect on depression. We examined this hypothesis using unique human glial-like mesenchymal stem cells (MSCs), which in addition to inherent properties of migration to regions of injury and secretion of neurotrophic factors, were differentiated to express high levels of functional glutamate transporters (excitatory amino acid transporters; EAAT). Additionally, gold nanoparticles (GNPs), which serve as contrast agents for CT imaging, were loaded into the cells for non-invasive, real-time imaging and tracking of MSC migration and final location within the brain. MSC-EAAT (2×105; 10 μl) were administered (i.c.v.) to Flinder Sensitive Line rats (FSLs), a genetic model for depression, and longitudinal behavioral and molecular changes were monitored. FSL rats treated with MSC-EAAT showed attenuated depressive-like behaviors (measured by the forced swim test, novelty exploration test and sucrose self-administration paradigm), as compared to controls. CT imaging, Flame Atomic Absorption Spectroscopy analysis and immunohistochemistry showed that the majority of MSCs homed specifically to the dentate gyrus of the hippocampus, a region showing structural brain changes in depression, including loss of glial cells. mRNA and protein levels of EAAT1 and BDNF were significantly elevated in the hippocampus of MSC-EAAT-treated FSLs. Our findings indicate that MSC-EAATs effectively improve depressive-like manifestations, possibly in part by increasing both glutamate uptake and neurotropic factor secretion in the hippocampus.

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Astrocyte-mediated metaplasticity in the hippocampus: Help or hindrance?

Cited by 26 publications

References 153 publications

ALA-PpIX mediated photodynamic therapy of malignant gliomas augmented by hypothermia

ALA-PpIX mediated photodynamic therapy of malignant gliomas augmented by hypothermia

Long-Term Potentiation-Associated Gene Expression: Involvement of the Tumour Protein p53

Therapeutic Effect of Astroglia-like Mesenchymal Stem Cells Expressing Glutamate Transporter in a Genetic Rat Model of Depression

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