Loss of Astrocytic Domain Organization in the Epileptic Brain

Oberheim, Nancy Ann; Tian, Guo Feng; Han, Xiaoning; Peng, Weiguo; Takano, Takahiro; Ransom, Bruce R.

doi:10.1523/jneurosci.4980-07.2008

Cited by 274 publications

(264 citation statements)

References 72 publications

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“…Finally, astrocytic domain organization is disrupted in epilepsy which may, for example, affect K + buffering or neurotransmitter clearance (Oberheim et al, 2008). Interestingly, wide‐spread reactive astrogliosis which develops in a mouse with a conditional deletion of β1‐integrin leads to spontaneous seizures, most likely due to the impaired uptake of glutamate (Robel et al, 2015).…”

Section: Astrocytes In the Diseased Brain Are Central To Neuropathologymentioning

confidence: 99%

Astroglia as a cellular target for neuroprotection and treatment of neuro‐psychiatric disorders

Liu

Teschemacher

Kasparov

2017

Glia

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Astrocytes are key homeostatic cells of the central nervous system. They cooperate with neurons at several levels, including ion and water homeostasis, chemical signal transmission, blood flow regulation, immune and oxidative stress defense, supply of metabolites and neurogenesis. Astroglia is also important for viability and maturation of stem‐cell derived neurons. Neurons critically depend on intrinsic protective and supportive properties of astrocytes. Conversely, all forms of pathogenic stimuli which disturb astrocytic functions compromise neuronal functionality and viability. Support of neuroprotective functions of astrocytes is thus an important strategy for enhancing neuronal survival and improving outcomes in disease states. In this review, we first briefly examine how astrocytic dysfunction contributes to major neurological disorders, which are traditionally associated with malfunctioning of processes residing in neurons. Possible molecular entities within astrocytes that could underpin the cause, initiation and/or progression of various disorders are outlined. In the second section, we explore opportunities enhancing neuroprotective function of astroglia. We consider targeting astrocyte‐specific molecular pathways which are involved in neuroprotection or could be expected to have a therapeutic value. Examples of those are oxidative stress defense mechanisms, glutamate uptake, purinergic signaling, water and ion homeostasis, connexin gap junctions, neurotrophic factors and the Nrf2‐ARE pathway. We propose that enhancing the neuroprotective capacity of astrocytes is a viable strategy for improving brain resilience and developing new therapeutic approaches.

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Section: Astrocytes In the Diseased Brain Are Central To Neuropathologymentioning

confidence: 99%

Astroglia as a cellular target for neuroprotection and treatment of neuro‐psychiatric disorders

Liu

Teschemacher

Kasparov

2017

Glia

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“…This makes astrocytes geometrically well suited to send currents into neuron groups large enough to extrapolate to cell assemblies. The branching of astrocytes has been shown to divide up space into essentially nonoverlapping 'domains' (Bushong et al, 2002;Oberheim et al, 2008), and whichever astrocyte arborizes over a domain touches essentially every dendritic process passing through the domain.…”

Section: Meid Molecules: Igniting a Selected Cell Assembly By Directimentioning

confidence: 99%

Synaptic and extrasynaptic traces of long-term memory: the ID molecule theory

Legéndy

2016

Reviews in the Neurosciences

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AbstractIt is generally assumed at the time of this writing that memories are stored in the form of synaptic weights. However, it is now also clear that the synapses are not permanent; in fact, synaptic patterns undergo significant change in a matter of hours. This means that to implement the long survival of distant memories (for several decades in humans), the brain must possess a molecular backup mechanism in some form, complete with provisions for the storage and retrieval of information. It is found below that the memory-supporting molecules need not contain a detailed description of mental entities, as had been envisioned in the ‘memory molecule papers’ from 50 years ago, they only need to contain unique identifiers of various entities, and that this can be achieved using relatively small molecules, using a random code (‘ID molecules’). In this paper, the logistics of information flow are followed through the steps of storage and retrieval, and the conclusion reached is that the ID molecules, by carrying a sufficient amount of information (entropy), can effectively control the recreation of complex multineuronal patterns. In illustrations, it is described how ID molecules can be made to revive a selected cell assembly by waking up its synapses and how they cause a selected cell assembly to ignite by sending slow inward currents into its cells. The arrangement involves producing multiple copies of the ID molecules and distributing them at strategic locations at selected sets of synapses, then reaching them through small noncoding RNA molecules. This requires the quick creation of entropy-rich messengers and matching receptors, and it suggests that these are created from each other by small-scale transcription and reverse transcription.

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“…These domains are most clearly defined in areas of high synaptic density, such as the hippocampus, which suggests that domain organization may be important for modulation of synaptic transmission [14] . Disruption of protoplasmic astrocytic domains is observed during glial scar formation in CNS trauma and infection as well as in the epileptic brain [15,16] . Fibrous astrocytes, on the other hand, show extensive intersection of their processes, and therefore, do not appear to have the same organization as protoplasmic astrocytes [17] .…”

Section: Astrocyte Heterogeneity: Differences Between Protoplasmic Anmentioning

confidence: 99%

“…Accumulating evidence indicates that reactive astrogliosis is not a simple all or none response. Instead, astrocyte activation is variable in regards to changes in cell morphology, proliferation, and molecular expression, all of which can be modified in a context-specific manner to different CNS insults [8,16,39,[46][47][48] . Additionally, these molecular and cellular changes are graded in a manner that coincides with the level of injury to the CNS [49] .…”

Section: Astrocyte Activation: Overviewmentioning

confidence: 99%

New advances on glial activation in health and disease

Lee

MacLean

2015

WJV

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In addition to being the support cells of the central nervous system (CNS), astrocytes are now recognized as active players in the regulation of synaptic function, neural repair, and CNS immunity. Astrocytes are among the most structurally complex cells in the brain, and activation of these cells has been shown in a wide spectrum of CNS injuries and diseases. Over the past decade, research has begun to elucidate the role of astrocyte activation and changes in astrocyte morphology in the progression of neural pathologies, which has led to glial-specific interventions for drug development. Future therapies for CNS infection, injury, and neurodegenerative disease are now aimed at targeting astrocyte responses to such insults including astrocyte activation, astrogliosis and other morphological changes, and innate and adaptive immune responses.

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Loss of Astrocytic Domain Organization in the Epileptic Brain

Cited by 274 publications

References 72 publications

Astroglia as a cellular target for neuroprotection and treatment of neuro‐psychiatric disorders

Astroglia as a cellular target for neuroprotection and treatment of neuro‐psychiatric disorders

Synaptic and extrasynaptic traces of long-term memory: the ID molecule theory

New advances on glial activation in health and disease

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