NMDA receptor triggered molecular cascade underlies compression-induced rapid dendritic spine plasticity in cortical neurons

Chen, Li-Jin; Wang, Yueh-Jan; Chen, Jeng-Rung; Tseng, Guo‐Fang

doi:10.1016/j.expneurol.2015.02.014

Cited by 11 publications

(8 citation statements)

References 66 publications

(81 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Calcineurin translocation to synapses and increases in its activity mediated by NMDA receptor trafficking were reported as critical components of mechanisms driving rapid compression-induced dendritic spine plasticity in cortical pyramidal neurons, that is, the rapid trimming of dendritic spines occurring about 12 hours after mechanical compression [38]. A study using soluble A β treated in cultured rat hippocampal neurons and cultured hippocampal neurons from APPSwe AD-transgenic mice suggested that calcineurin signaling mediates AD-like synaptic dysfunction induced by tau protein partly via AMPA receptor downregulation [193].…”

Section: Controversial Roles In Nervous System Diseasesmentioning

confidence: 99%

See 1 more Smart Citation

The Emerging Roles of the Calcineurin-Nuclear Factor of Activated T-Lymphocytes Pathway in Nervous System Functions and Diseases

Kipanyula

Kimaro

Etet

2016

Journal of Aging Research

View full text Add to dashboard Cite

The ongoing epidemics of metabolic diseases and increase in the older population have increased the incidences of neurodegenerative diseases. Evidence from murine and cell line models has implicated calcineurin-nuclear factor of activated T-lymphocytes (NFAT) signaling pathway, a Ca2+/calmodulin-dependent major proinflammatory pathway, in the pathogenesis of these diseases. Neurotoxins such as amyloid-β, tau protein, and α-synuclein trigger abnormal calcineurin/NFAT signaling activities. Additionally increased activities of endogenous regulators of calcineurin like plasma membrane Ca2+-ATPase (PMCA) and regulator of calcineurin 1 (RCAN1) also cause neuronal and glial loss and related functional alterations, in neurodegenerative diseases, psychotic disorders, epilepsy, and traumatic brain and spinal cord injuries. Treatment with calcineurin/NFAT inhibitors induces some degree of neuroprotection and decreased reactive gliosis in the central and peripheral nervous system. In this paper, we summarize and discuss the current understanding of the roles of calcineurin/NFAT signaling in physiology and pathologies of the adult and developing nervous system, with an emphasis on recent reports and cutting-edge findings. Calcineurin/NFAT signaling is known for its critical roles in the developing and adult nervous system. Its role in physiological and pathological processes is still controversial. However, available data suggest that its beneficial and detrimental effects are context-dependent. In view of recent reports calcineurin/NFAT signaling is likely to serve as a potential therapeutic target for neurodegenerative diseases and conditions. This review further highlights the need to characterize better all factors determining the outcome of calcineurin/NFAT signaling in diseases and the downstream targets mediating the beneficial and detrimental effects.

show abstract

Section: Controversial Roles In Nervous System Diseasesmentioning

confidence: 99%

“…Calcineurin/NFAT involvement has also been reported in psychiatric disorders, epilepsy, and traumatic brain and spinal cord injuries [30–35]. Moreover, recent data also suggest that NFAT isoforms are selectively activated in neurons and glial cells in nervous system diseases [36, 37] and animal models [38–41]. …”

Section: Introductionmentioning

confidence: 99%

The Emerging Roles of the Calcineurin-Nuclear Factor of Activated T-Lymphocytes Pathway in Nervous System Functions and Diseases

Kipanyula

Kimaro

Etet

2016

Journal of Aging Research

View full text Add to dashboard Cite

show abstract

“…The mass compression effect of ventriculomegaly, brain ischemia (2) and inflammation (21,22) are likely additional factors to intensify the dendritic spine loss under hydrocephalus. In the somatosensory cortex, mechanical compression appeared to mobilize and activate NMDA receptors to increase postsynaptic calcium, which in turn activated the phosphatase calcineurin to dephosphorylate and activate the actin-severing protein cofilin to disintegrate actin in dendritic spines for retraction (8). Loss of dendritic spines however was more severe in the chronic than acute hydrocephalic stage.…”

Section: The Effects Of Hydrocephalus On Primary Somatosensory Cortexmentioning

confidence: 99%

“…Cerebral ischemia (29), brain inflammation (21), loss of presynaptic elements caused by deafferentation (26) and cerebral compression (8) are all known to affect presynaptic and/or postsynaptic activities and lead to pruning of neuronal dendritic spines. The reduction of afferents in the hydrocephalus reported earlier (14) and indirectly in the present study (the reduction of synaptophysin level) could contribute to the pruning of dendritic spines that we observed.…”

Section: The Effects Of Hydrocephalus On Primary Somatosensory Cortexmentioning

confidence: 99%

“…Other factors could add to contribute to the late dendritic spine loss during chronic hydrocephalus as well. In the somatosensory cortex, mechanical compression appeared to mobilize and activate NMDA receptors to increase postsynaptic calcium, which in turn activated the phosphatase calcineurin to dephosphorylate and activate the actin-severing protein cofilin to disintegrate actin in dendritic spines for retraction (8). This mechanism could have played a role in the retraction of dendritic spines in hydrocephalus as the associated ventriculomegaly also compressed the cerebral cortex.…”

Section: The Effects Of Hydrocephalus On Primary Somatosensory Cortexmentioning

confidence: 99%

See 1 more Smart Citation

Hydrocephalus compacted cortex and hippocampus and altered their output neurons in association with spatial learning and memory deficits in rats

et al. 2016

Self Cite

View full text Add to dashboard Cite

Hydrocephalus is a common neurological disorder in children characterized by abnormal dilation of cerebral ventricles as a result of the impairment of cerebrospinal fluid flow or absorption. Clinical presentation of hydrocephalus varies with chronicity and often shows cognitive dysfunction. Here we used a kaolin-induction method in rats and studied the effects of hydrocephalus on cerebral cortex and hippocampus, the two regions highly related to cognition. Hydrocephalus impaired rats' performance in Morris water maze task. Serial three-dimensional reconstruction from sections of the whole brain freshly froze in situ with skull shows that the volumes of both structures were reduced. Morphologically, pyramidal neurons of the somatosensory cortex and hippocampus appear to be distorted. Intracellular dye injection and subsequent three-dimensional reconstruction and analyses revealed that the dendritic arbors of layer III and V cortical pyramid neurons were reduced. The total dendritic length of CA1, but not CA3, pyramidal neurons was also reduced. Dendritic spine densities on both cortical and hippocampal pyramidal neurons were decreased, consistent with our concomitant findings that the expressions of both synaptophysin and postsynaptic density protein 95 were reduced. These cortical and hippocampal changes suggest reductions of excitatory connectivity, which could underlie the learning and memory deficits in hydrocephalus.

show abstract

A novel perspective on neuron study: damaging and promoting effects in different neurons induced by mechanical stress

Wang

Zong

et al. 2015

Biomech Model Mechanobiol

View full text Add to dashboard Cite

A growing volume of experimental evidence demonstrates that mechanical stress plays a significant role in growth, proliferation, apoptosis, gene expression, electrophysiological properties and many other aspects of neurons. In this review, first, the mechanical microenvironment and properties of neurons under in vivo conditions are introduced and analyzed. Second, research works in recent decades on the effects of different mechanical forces, especially compression and tension, on various neurons, including dorsal root ganglion neurons, retinal ganglion cells, cerebral cortex neurons, hippocampus neurons, neural stem cells, and other neurons, are summarized. Previous research results demonstrate that mechanical stress can not only injure neurons by damaging their morphology, impacting their electrophysiological characteristics and gene expression, but also promote neuron self-repair. Finally, some future perspectives in neuron research are discussed.

show abstract

NMDA receptor triggered molecular cascade underlies compression-induced rapid dendritic spine plasticity in cortical neurons

Cited by 11 publications

References 66 publications

The Emerging Roles of the Calcineurin-Nuclear Factor of Activated T-Lymphocytes Pathway in Nervous System Functions and Diseases

The Emerging Roles of the Calcineurin-Nuclear Factor of Activated T-Lymphocytes Pathway in Nervous System Functions and Diseases

Hydrocephalus compacted cortex and hippocampus and altered their output neurons in association with spatial learning and memory deficits in rats

A novel perspective on neuron study: damaging and promoting effects in different neurons induced by mechanical stress

Contact Info

Product

Resources

About