Abstract:
BACKGROUND:Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the selective loss of motor neurons (MN) in the brain stem and spinal cord. Intracellular disruptions of cytosolic and mitochondrial calcium have been associated with selective MN degeneration, but the underlying mechanisms are not well understood. The present evidence supports a hypothesis that mitochondria are a target of mutant SOD1-mediated toxicity in familial amyotrophic lateral sclerosis (fALS) and intracellular alterations of cytosolic and mitochondrial calcium might aggravate the course of this neurodegenerative disease. In this study, we used a fluorescence charged cool device (CCD) imaging system to separate and simultaneously monitor cytosolic and mitochondrial calcium concentrations in individual cells in an established cellular model of ALS. RESULTS:To gain insights into the molecular mechanisms of SOD1(G93A) associated motor neuron disease, we simultaneously monitored cytosolic and mitochondrial calcium concentrations in individual cells. Voltage - dependent cytosolic Ca2+ elevations and mitochondria - controlled calcium release mechanisms were monitored after loading cells with fluorescent dyes fura-2 and rhod-2. Interestingly, comparable voltage-dependent cytosolic Ca2+ elevations in WT (SH-SY5Y(WT)) and G93A (SH-SY5Y(G93A)) expressing cells were observed. In contrast, mitochondrial intracellular Ca2+ release responses evoked by bath application of the mitochondrial toxin FCCP were significantly smaller in G93A expressing cells, suggesting impaired calcium stores. Pharmacological experiments further supported the concept that the presence of G93A severely disrupts mitochondrial Ca2+ regulation. CONCLUSION:In this study, by fluorescence measurement of cytosolic calcium and using simultaneous [Ca2+]i and [Ca2+]mito measurements, we are able to separate and simultaneously monitor cytosolic and mitochondrial calcium concentrations in individual cells an established cellular model of ALS. The primary goals of this paper are (1) method development, and (2) screening for deficits in mutant cells on the single cell level. On the technological level, our method promises to serve as a valuable tool to identify mitochondrial and Ca2+-related defects during G93A-mediated MN degeneration. In addition, our experiments support a model where a specialized interplay between cytosolic calcium profiles and mitochondrial mechanisms contribute to the selective degeneration of neurons in ALS.
journal_name
BMC Neuroscijournal_title
BMC neuroscienceauthors
Jaiswal MK,Zech WD,Goos M,Leutbecher C,Ferri A,Zippelius A,Carrì MT,Nau R,Keller BUdoi
10.1186/1471-2202-10-64subject
Has Abstractpub_date
2009-06-22 00:00:00pages
64issn
1471-2202pii
1471-2202-10-64journal_volume
10pub_type
杂志文章相关文献
BMC NEUROSCIENCE文献大全abstract:BACKGROUND:How living neural networks retain information is still incompletely understood. Two prominent ideas on this topic have developed in parallel, but have remained somewhat unconnected. The first of these, the "synaptic hypothesis," holds that information can be retained in synaptic connection strengths, or weig...
journal_title:BMC neuroscience
pub_type: 杂志文章
doi:10.1186/1471-2202-11-3
更新日期:2010-01-06 00:00:00
abstract:BACKGROUND:A delay in surgical nerve repair results in impaired nerve function in humans, but mechanisms behind the weakened nerve regeneration are not known. Activating transcription factor 3 (ATF3) increases the intrinsic growth state of injured neurons early after injury, but the role of long-term changes and their ...
journal_title:BMC neuroscience
pub_type: 杂志文章
doi:10.1186/1471-2202-9-88
更新日期:2008-09-18 00:00:00
abstract:BACKGROUND:Alzheimer's Disease (AD) is the most common of the conformational neurodegenerative disorders characterized by the conversion of a normal biological protein into a β-sheet-rich pathological isoform. In AD the normal soluble Aβ (sAβ) forms oligomers and fibrils which assemble into neuritic plaques. The most t...
journal_title:BMC neuroscience
pub_type: 杂志文章
doi:10.1186/1471-2202-11-130
更新日期:2010-10-14 00:00:00
abstract:BACKGROUND:Synaptic degeneration and accumulation of amyloid β-peptides (Aβ) are hallmarks of the Alzheimer diseased brain. Aβ is synaptotoxic and produced by sequential cleavage of the amyloid precursor protein (APP) by the β-secretase BACE1 and by γ-secretase. If APP is instead cleaved by the α-secretase ADAM10, Aβ w...
journal_title:BMC neuroscience
pub_type: 杂志文章
doi:10.1186/s12868-020-0554-0
更新日期:2020-02-04 00:00:00
abstract:BACKGROUND:The human KALRN gene, which encodes a complex, multifunctional Rho GDP/GTP exchange factor, has been linked to cardiovascular disease, psychiatric disorders and neurodegeneration. Examination of existing Kalrn knockout mouse models has focused only on neuronal phenotypes. However, Kalirin was first identifie...
journal_title:BMC neuroscience
pub_type: 杂志文章
doi:10.1186/1471-2202-13-136
更新日期:2012-11-01 00:00:00
abstract:BACKGROUND:Understanding the underlying causes of nicotine addiction will require a multidisciplinary approach examining the key molecular, cellular and neuronal circuit functional changes that drive escalating levels of nicotine self-administration. In this study, we examined whether mice pretreated with chronic nicot...
journal_title:BMC neuroscience
pub_type: 杂志文章
doi:10.1186/1471-2202-15-89
更新日期:2014-07-19 00:00:00
abstract:BACKGROUND:Chlamydophila (Chlamydia) pneumoniae is an intracellular bacterium that has been identified within cells in areas of neuropathology found in Alzheimer disease (AD), including endothelia, glia, and neurons. Depending on the cell type of the host, infection by C. pneumoniae has been shown to influence apoptoti...
journal_title:BMC neuroscience
pub_type: 杂志文章
doi:10.1186/1471-2202-9-13
更新日期:2008-01-24 00:00:00
abstract:BACKGROUND:Acute subdural hemorrhage (ASDH) is a severe consequence of traumatic brain injury. The occurrence of subdural blood increases the lethality of these patients independent of the amount of blood or elevated intracranial pressure. Thrombin is one of the potential harmful blood components. Possible harmful effe...
journal_title:BMC neuroscience
pub_type: 杂志文章
doi:10.1186/s12868-018-0481-5
更新日期:2018-12-27 00:00:00
abstract:BACKGROUND:Intracranial Self-Stimulation (ICSS) of the medial forebrain bundle (MFB) is a deep brain stimulation procedure, which has a powerful enhancement effect on explicit and implicit memory. However, the downstream synaptic plasticity events of MFB-ICSS in memory related areas have not been described thoroughly. ...
journal_title:BMC neuroscience
pub_type: 杂志文章
doi:10.1186/s12868-018-0449-5
更新日期:2018-08-08 00:00:00
abstract:BACKGROUND:Peripherin, a type III neuronal intermediate filament, is widely expressed in neurons of the peripheral nervous system and in selected central nervous system hindbrain areas with projections towards peripheral structures, such as cranial nerves and spinal cord neurons. Peripherin appears to play a role in ne...
journal_title:BMC neuroscience
pub_type: 杂志文章
doi:10.1186/1471-2202-9-26
更新日期:2008-02-24 00:00:00
abstract:BACKGROUND:The GABAergic system plays an important role in modulating levels of anxiety. When transplanted into the brain, precursor cells from the medial ganglionic eminence (MGE) have the ability to differentiate into GABAergic interneurons and modify the inhibitory tone in the host brain. Currently, two methods have...
journal_title:BMC neuroscience
pub_type: 杂志文章
doi:10.1186/1471-2202-15-94
更新日期:2014-08-02 00:00:00
abstract:BACKGROUND:Lateralized processing of speech is a well studied phenomenon in humans. Both anatomical and neurophysiological studies support the view that nonhuman primates and other animal species also reveal hemispheric differences in areas involved in sound processing. In recent years, an increasing number of studies ...
journal_title:BMC neuroscience
pub_type: 杂志文章
doi:10.1186/1471-2202-10-14
更新日期:2009-02-24 00:00:00
abstract:BACKGROUND:Accumulating evidence suggests that glial signalling is activated by different brain functions. However, knowledge regarding molecular mechanisms of activation or their relation to neuronal activity is limited. The purpose of the present study is to identify the characteristics of ATP-evoked glial signalling...
journal_title:BMC neuroscience
pub_type: 杂志文章
doi:10.1186/1471-2202-12-96
更新日期:2011-10-03 00:00:00
abstract:BACKGROUND:Odorant stimuli can access the olfactory epithelium either orthonasally, by inhalation through the external nares, or retronasally by reverse airflow from the oral cavity. There is evidence that odors perceived through these two routes can differ in quality and intensity. We were curious whether such differe...
journal_title:BMC neuroscience
pub_type: 杂志文章
doi:10.1186/1471-2202-14-45
更新日期:2013-04-08 00:00:00
abstract:BACKGROUND:The human inferior frontal junction area (IFJ) is critically involved in three main component processes of cognitive control (working memory, task switching and inhibitory control). As it overlaps with several areas in established anatomical labeling schemes, it is considered to be underreported as a functio...
journal_title:BMC neuroscience
pub_type: 杂志文章,meta分析
doi:10.1186/1471-2202-13-119
更新日期:2012-10-03 00:00:00
abstract:BACKGROUND:Recovery following stroke depends on cellular plasticity in the perilesional zone (PZ). Doublecortin (DCX), a protein mainly labeling immature neurons in neurogenic niches is also highly expressed in the vicinity of focal cortical infarcts. Notably, the number of DCX+ cells positively correlates with the rec...
journal_title:BMC neuroscience
pub_type: 杂志文章
doi:10.1186/s12868-015-0160-8
更新日期:2015-04-15 00:00:00
abstract:BACKGROUND:Perivascular stromal cells (PSCs) are a recently identified cell type that comprises a small percentage of the platelet derived growth factor receptor-β+ cells within the CNS perivascular space. PSCs are activated following injury to the brain or spinal cord, expand in number and contribute to fibrotic scar ...
journal_title:BMC neuroscience
pub_type: 杂志文章
doi:10.1186/s12868-016-0284-5
更新日期:2016-07-15 00:00:00
abstract:BACKGROUND:Immunization with neural derived peptides (INDP) as well as scar removal-separately-have shown to induce morphological and functional improvement after spinal cord injury (SCI). In the present study, we compared the effect of INDP alone versus INDP with scar removal on motor recovery, regeneration-associated...
journal_title:BMC neuroscience
pub_type: 杂志文章
doi:10.1186/s12868-016-0331-2
更新日期:2017-01-05 00:00:00
abstract:BACKGROUND:Multi-sensor technologies such as EEG, MEG, and ECoG result in high-dimensional data sets. Given the high temporal resolution of such techniques, scientific questions very often focus on the time-course of an experimental effect. In many studies, researchers focus on a single sensor or the average over a sub...
journal_title:BMC neuroscience
pub_type: 杂志文章
doi:10.1186/1471-2202-14-122
更新日期:2013-10-14 00:00:00
abstract:BACKGROUND:Hyperbaric oxygen therapy (HBOT) is a known adjuvant for treating ischemia-related inner ear diseases. Controversies still exist in the role of HBOT in cochlear diseases. Few studies to date have investigated the cellular changes that occur in inner ears after HBOT. Nitric oxide, which is synthesized by nitr...
journal_title:BMC neuroscience
pub_type: 杂志文章
doi:10.1186/1471-2202-12-21
更新日期:2011-02-22 00:00:00
abstract:BACKGROUND:10 Hz electroencephalographic (EEG) alpha rhythms correlate with memory performance. Alpha and memory decline in older people. We wished to test if alpha-like EEG activity contributes to memory formation. Flicker can elicit alpha-like EEG activity. We tested if alpha-frequency flicker enhances memory in olde...
journal_title:BMC neuroscience
pub_type: 临床试验,杂志文章
doi:10.1186/1471-2202-7-21
更新日期:2006-03-05 00:00:00
abstract:BACKGROUND:Several studies have shown that Stroop interference is stronger in children than in adults. However, in a standard Stroop paradigm, stimulus interference and response interference are confounded. The purpose of the present study was to determine whether interference at the stimulus level and the response lev...
journal_title:BMC neuroscience
pub_type: 杂志文章
doi:10.1186/1471-2202-9-82
更新日期:2008-09-05 00:00:00
abstract:BACKGROUND:The zitter (zi/zi) rat, a loss-of-function mutant of the glycosylated transmembrane protein attractin (atrn), exhibits widespread age-dependent spongiform degeneration, hypomyelination, and abnormal metabolism of reactive oxygen species (ROS) in the brain. To date, the mechanisms underlying these phenotypes ...
journal_title:BMC neuroscience
pub_type: 杂志文章
doi:10.1186/1471-2202-9-35
更新日期:2008-04-05 00:00:00
abstract:BACKGROUND:Enhanced activity of trigeminal ganglion neurons is thought to underlie neuronal sensitization facilitating the onset of chronic pain attacks, including migraine. Recurrent headache attacks might establish a chronic neuroinflammatory ganglion profile contributing to the hypersensitive phenotype. Since it is ...
journal_title:BMC neuroscience
pub_type: 杂志文章
doi:10.1186/1471-2202-13-143
更新日期:2012-11-21 00:00:00
abstract:BACKGROUND:Recent alleged attacks with nerve agent sarin on civilians in Syria indicate their potential threat to both civilian and military population. Acute nerve agent exposure can cause rapid death or leads to multiple and long term neurological effects. The biochemical changes that occur following nerve agent expo...
journal_title:BMC neuroscience
pub_type: 杂志文章
doi:10.1186/1471-2202-15-47
更新日期:2014-04-04 00:00:00
abstract:BACKGROUND:The mechanisms of steroids actions in the brain mainly involve the binding and nuclear translocation of specific cytoplasmic receptors. These receptors can act as transcription factors and regulate gene expression. However, steroid-dependent transcriptional regulation in different types of neural cells is no...
journal_title:BMC neuroscience
pub_type: 杂志文章
doi:10.1186/s12868-017-0352-5
更新日期:2017-04-05 00:00:00
abstract:BACKGROUND:Excitatory transmitting mechanisms are proving to play a critical role on neuronal homeostasis conditions of facultative hibernators such as the Syrian golden hamster. Indeed works have shown that the glutamatergic system of the main olfactory brain station (amygdala) is capable of controlling thermoregulato...
journal_title:BMC neuroscience
pub_type: 杂志文章
doi:10.1186/1471-2202-12-10
更新日期:2011-01-20 00:00:00
abstract:BACKGROUND:The topological structure of the wiring of the mammalian brain cortex plays an important role in shaping the functional dynamics of large-scale neural activity. Due to their central embedding in the network, high degree hub regions and their connections (often referred to as the 'rich club') have been hypoth...
journal_title:BMC neuroscience
pub_type: 杂志文章
doi:10.1186/s12868-015-0193-z
更新日期:2015-09-02 00:00:00
abstract:BACKGROUND:This work examines the central nervous system distribution of virus-labeled neurons from the rat urinary bladder and the prostate simultaneously within the same tissue sections. Two immunohistochemically distinct pseudorabies virus strains were simultaneously injected into male Sprague Dawley rats (approxima...
journal_title:BMC neuroscience
pub_type: 杂志文章
doi:10.1186/1471-2202-3-8
更新日期:2002-07-12 00:00:00
abstract:BACKGROUND:Major depressive disorder is a prevalent disease that is inadequately treated with currently available interventions. Stress increases susceptibility to depression in patients and rodent models. Depression is also associated with aberrant activation of inflammation, such as increases in circulating levels of...
journal_title:BMC neuroscience
pub_type: 杂志文章
doi:10.1186/s12868-015-0169-z
更新日期:2015-05-07 00:00:00