Astroglial connexins and cognition: memory formation or deterioration?

He, Jinting; Li, Xiaoyan; Yang, Le; Zhao, Xin

doi:10.1042/bsr20193510

Cited by 20 publications

(25 citation statements)

References 84 publications

(118 reference statements)

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“…In cultured astrocytes, DBN has been described to maintain connexin 43 at the plasma membrane 9 . Functional coupling of astrocytes into networks through gap junctions is essential to modulate neuronal transmission 10,11 . A deficit in DBN would therefore be expected to cause profound phenotypes in vivo.…”

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confidence: 99%

Drebrin controls scar formation and astrocyte reactivity upon traumatic brain injury by regulating membrane trafficking

et al. 2021

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The brain of mammals lacks a significant ability to regenerate neurons and is thus particularly vulnerable. To protect the brain from injury and disease, damage control by astrocytes through astrogliosis and scar formation is vital. Here, we show that brain injury in mice triggers an immediate upregulation of the actin-binding protein Drebrin (DBN) in astrocytes, which is essential for scar formation and maintenance of astrocyte reactivity. In turn, DBN loss leads to defective astrocyte scar formation and excessive neurodegeneration following brain injuries. At the cellular level, we show that DBN switches actin homeostasis from ARP2/3-dependent arrays to microtubule-compatible scaffolds, facilitating the formation of RAB8-positive membrane tubules. This injury-specific RAB8 membrane compartment serves as hub for the trafficking of surface proteins involved in astrogliosis and adhesion mediators, such as β1-integrin. Our work shows that DBN-mediated membrane trafficking in astrocytes is an important neuroprotective mechanism following traumatic brain injury in mice.

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confidence: 99%

Drebrin controls scar formation and astrocyte reactivity upon traumatic brain injury by regulating membrane trafficking

et al. 2021

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“…GJA1/connexin43 or gap junction alpha 1, functions to allow rapid inter-cellular communication of small molecules such as ions and neurotransmitters by establishing hemichannel gap junctions between cells [ 46 ]. Many studies coupled GJA1 with the pathogenesis of neurodegenerative diseases such as AD [ 47 , 48 ], most notably finding GJA1 incorporated into amyloid plaques [ 49 ] and upregulated in AD models and human brain [ 6 , 50 , 51 , 52 ]. VSNL1 or visinin-like protein 1, is a neuronal calcium sensor (NCS) protein highly expressed in the brain.…”

Section: Discussionmentioning

confidence: 99%

Broad Kinase Inhibition Mitigates Early Neuronal Dysfunction in Tauopathy

Koren

Hamm

Cloyd

et al. 2021

IJMS

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Tauopathies are a group of more than twenty known disorders that involve progressive neurodegeneration, cognitive decline and pathological tau accumulation. Current therapeutic strategies provide only limited, late-stage symptomatic treatment. This is partly due to lack of understanding of the molecular mechanisms linking tau and cellular dysfunction, especially during the early stages of disease progression. In this study, we treated early stage tau transgenic mice with a multi-target kinase inhibitor to identify novel substrates that contribute to cognitive impairment and exhibit therapeutic potential. Drug treatment significantly ameliorated brain atrophy and cognitive function as determined by behavioral testing and a sensitive imaging technique called manganese-enhanced magnetic resonance imaging (MEMRI) with quantitative R1 mapping. Surprisingly, these benefits occurred despite unchanged hyperphosphorylated tau levels. To elucidate the mechanism behind these improved cognitive outcomes, we performed quantitative proteomics to determine the altered protein network during this early stage in tauopathy and compare this model with the human Alzheimer’s disease (AD) proteome. We identified a cluster of preserved pathways shared with human tauopathy with striking potential for broad multi-target kinase intervention. We further report high confidence candidate proteins as novel therapeutically relevant targets for the treatment of tauopathy. Proteomics data are available via ProteomeXchange with identifier PXD023562.

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“…It has also been speculated that spatiotemporal synchrony of activity across local and distant neuronal and astrocytic cortical networks could be a prerequisite of particular brain and behavioral states (Buskila et al 2019). There is evidence that physiological concentrations of connexins expressed in glial cells might be beneficial for cognitive processes, while connexin overexpression under pathological conditions, e.g., in Alzheimer disease, and after excessive activation of glial cells might be associated with cognitive decline (He et al 2020). Astrocytes expressing Cx43 and Cx30 have been implicated in neurogenesis (Liebmann et al 2013) and long-term synaptic plasticity (Pannasch et al 2014).…”

Section: Glial Cells Synchronization and Cognitionmentioning

confidence: 99%

Channels to consciousness: a possible role of gap junctions in consciousness

Dere

Zlomuzica²,

Dere

2020

Reviews in the Neurosciences

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The neurophysiological basis of consciousness is still unknown and one of the most challenging questions in the field of neuroscience and related disciplines. We propose that consciousness is characterized by the maintenance of mental representations of internal and external stimuli for the execution of cognitive operations. Consciousness cannot exist without working memory, and it is likely that consciousness and working memory share the same neural substrates. Here, we present a novel psychological and neurophysiological framework that explains the role of consciousness for cognition, adaptive behavior, and everyday life. A hypothetical architecture of consciousness is presented that is organized as a system of operation and storage units named platforms that are controlled by a consciousness center (central executive/online platform). Platforms maintain mental representations or contents, are entrusted with different executive functions, and operate at different levels of consciousness. The model includes conscious-mode central executive/online and mental time travel platforms and semiconscious steady-state and preconscious standby platforms. Mental representations or contents are represented by neural circuits and their support cells (astrocytes, oligodendrocytes, etc.) and become conscious when neural circuits reverberate, that is, fire sequentially and continuously with relative synchronicity. Reverberatory activity in neural circuits may be initiated and maintained by pacemaker cells/neural circuit pulsars, enhanced electronic coupling via gap junctions, and unapposed hemichannel opening. The central executive/online platform controls which mental representations or contents should become conscious by recruiting pacemaker cells/neural network pulsars, the opening of hemichannels, and promoting enhanced neural circuit coupling via gap junctions.

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Astroglial connexins and cognition: memory formation or deterioration?

Cited by 20 publications

References 84 publications

Drebrin controls scar formation and astrocyte reactivity upon traumatic brain injury by regulating membrane trafficking

Drebrin controls scar formation and astrocyte reactivity upon traumatic brain injury by regulating membrane trafficking

Broad Kinase Inhibition Mitigates Early Neuronal Dysfunction in Tauopathy

Channels to consciousness: a possible role of gap junctions in consciousness

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