Abstract:
:PCDH19-Clustering Epilepsy (PCDH19-CE) is an infantile onset disorder caused by mutation of the X-linked PCDH19 gene. Intriguingly, heterozygous females are affected while hemizygous males are not. While there is compelling evidence that this disorder stems from the coexistence of WT and PCDH19-null cells, the cellular mechanism underpinning the neurological phenotype remains unclear. Here, we investigate the impact of Pcdh19 WT and KO neuron mosaicism on synaptogenesis and network activity. Using our previously established knock-in and knock-out mouse models, together with CRISPR-Cas9 genome editing technology, we demonstrate a reduction in excitatory synaptic contacts between PCDH19-expressing and PCDH19-null neurons. Significantly altered neuronal morphology and neuronal network activities were also identified in the mixed populations. In addition, we show that in Pcdh19 heterozygous mice, where the coexistence of WT and KO neurons naturally occurs, aberrant contralateral axonal branching is present. Overall, our data show that mosaic expression of PCDH19 disrupts physiological neurite communication leading to abnormal neuronal activity, a hallmark of PCDH19-CE.
journal_name
Mol Neurobioljournal_title
Molecular neurobiologyauthors
Mincheva-Tasheva S,Nieto Guil AF,Homan CC,Gecz J,Thomas PQdoi
10.1007/s12035-020-02242-4subject
Has Abstractpub_date
2021-01-07 00:00:00eissn
0893-7648issn
1559-1182pii
10.1007/s12035-020-02242-4pub_type
杂志文章abstract::Multiple players are involved in motor and sensory dysfunctions after spinal cord injury (SCI). Therefore, therapeutic approaches targeting these various players in the damage cascade hold considerable promise for the treatment of traumatic spinal cord injury. Soluble epoxide hydrolase (sEH) is an endogenous key enzym...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-015-9118-1
更新日期:2016-04-01 00:00:00
abstract::Early life stress is considered a risk factor for the development of long-term psychiatric disorders. Maternal deprivation (MD) is a useful paradigm to understand the neurobiological underpinnings of early stress-induced changes in neurodevelopment trajectory. The goal of the present study was to examine the effects o...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-020-02164-1
更新日期:2020-10-15 00:00:00
abstract::Among five members of the K+-dependent Na+/Ca2+ exchanger (NCKX) family (NCKX1-5), only NCKX2 is highly expressed in mouse brain. NCKX2 in plasma membranes mediates cytosolic calcium excretion through electrogenic exchange of 4 Na+ for 1 Ca2+ and 1 K+. Here, we observed significantly decreased levels of NCKX2 protein ...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-017-0596-1
更新日期:2018-05-01 00:00:00
abstract::There is increasing evidence suggesting that one of the most relevant pathophysiological features of Alzheimer's disease (AD) is neuroinflammation, which plays an important role in the production and regulation of AD-related proteins (amyloid beta (Aβ) and Tau) and exacerbates AD pathology. Neuroinflammation can also ...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-017-0795-9
更新日期:2018-07-01 00:00:00
abstract::Focal cortical dysplasia (FCD) is a major cause for drug-resistant epilepsies. The molecular and cellular mechanisms of epileptogenesis in FCD are still poorly understood. Some studies have suggested that deficiencies of γ-aminobutyric acid (GABA) system may play an important role in type II FCD, but it remains contro...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-020-02086-y
更新日期:2021-01-01 00:00:00
abstract::Axonal damage is a major factor contributing to disease progression in multiple sclerosis (MS) patients. On the histological level, acute axonal injury is most frequently analyzed by anti-amyloid precursor protein immunohistochemistry. To what extent this method truly detects axonal injury, and whether other proteins ...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-018-1353-9
更新日期:2019-06-01 00:00:00
abstract::γ-Secretase inhibitors (GSIs) are potential therapeutic agents for Alzheimer's disease (AD); however, trials have proven disappointing. We addressed the possibility that γ-secretase inhibition can provoke a rebound effect, elevating the levels of the catalytic γ-secretase subunit, presenilin-1 (PS1). Acute treatment o...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-017-0705-1
更新日期:2018-06-01 00:00:00
abstract::Dimebon (latrepirdine) is an anti-histaminergic agent which belongs to a fast-growing group of "old" medicines suggested to be of therapeutic utility for pathological conditions different from their original design ("repositioning"). Here, we overview the most recent studies on Dimebon directed to pathological process...
journal_title:Molecular neurobiology
pub_type: 杂志文章,评审
doi:10.1007/s12035-015-9249-4
更新日期:2015-10-01 00:00:00
abstract::The aim of this work was to study the effect of glucagon-like peptide-2 (GLP-2) on the cyclic guanosine monophosphate (cGMP) signalling pathway and whether insulin or epidermal growth factor (EGF) might modulate the effects of GLP-2. GLP-2 produced a dose-dependent decrease in intracellular sodium nitroprusside-induce...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-012-8298-1
更新日期:2012-10-01 00:00:00
abstract::Lysine-specific demethylase 1 (LSD1/KDM1A) plays an important role in complex cellular processes such as differentiation, proliferation, apoptosis, and cell cycle progression. It has recently been demonstrated that during development, downregulation of LSD1 inhibits cell proliferation, modulates the expression of cell...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-015-9206-2
更新日期:2016-05-01 00:00:00
abstract::Metabolic defects are common pathological phenomena following traumatic brain injury (TBI) which contribute to poor prognosis. Brain-derived neurotrophic factor (BDNF) is an important regulator of neuronal survival, development, function, and plasticity. This study was designed to investigate the potential effects of ...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-017-0576-5
更新日期:2018-04-01 00:00:00
abstract::In neurodegenerative diseases, pathogenic proteins tend to misfold and form aggregates that are difficult to remove and able to induce excessive endoplasmic reticulum (ER) stress, leading to neuronal injury and apoptosis. Homocysteine-induced endoplasmic reticulum protein (Herp), an E3 ubiquitin ligase, is an importan...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-018-0900-8
更新日期:2018-10-01 00:00:00
abstract::Astroglial scaring and limited neurogenesis are two problematic issues in recovery of spinal cord injury (SCI). In the meantime, it seems that mechanical manipulations of scaffold to inhibit astroglial scarring and improve neurogenesis is worthy of value. In the present investigation, the effect of nanofiber (gel) con...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-016-9836-z
更新日期:2017-05-01 00:00:00
abstract::Metals perform important functions in the normal physiological system, and alterations in their levels may lead to a number of diseases. Aluminium (Al) has been implicated as a major risk factor, which is linked to several neurodegenerative diseases including Alzheimer's disease and Parkinson's disease. On the other h...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-014-8643-7
更新日期:2014-10-01 00:00:00
abstract::Retinoid X-receptors (RXRs) are members of the ligand-dependent transcription factor family of nuclear receptors that have gained recent research focus as potential targets for neurodegenerative disorders. Bexarotene is an RXR pharmacological agonist that is shown to be neuroprotective through its effects in promoting...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-018-1041-9
更新日期:2018-12-01 00:00:00
abstract::The original version of this article unfortunately contained mistake in its Funding inforation. ...
journal_title:Molecular neurobiology
pub_type: 已发布勘误
doi:10.1007/s12035-018-1095-8
更新日期:2018-10-01 00:00:00
abstract::Adenine nucleotides through P2Y1 receptor stimulation are known to control retinal progenitor cell (RPC) proliferation by modulating expression of the p57KIP2, a cell cycle regulator. However, the role of Gi protein-coupled P2Y12 and P2Y13 receptors also activated by adenine nucleotides in RPC proliferation is still u...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-018-1012-1
更新日期:2018-11-01 00:00:00
abstract::Impaired glucose metabolism and mitochondrial decay greatly increase with age, when cognitive decline becomes rampant. No pharmacological or dietary intervention has proven effective, but proper diet and lifestyle do postpone the onset of neurodegeneration and some nutrients are being investigated. We studied insulin ...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-018-0934-y
更新日期:2018-09-01 00:00:00
abstract::Most survivors of ischemic stroke remain physically disabled and require prolonged rehabilitation. However, some stroke victims achieve a full neurological recovery suggesting that the human brain can defend itself against ischemic injury, but the protective mechanisms are unknown. This study used selective pharmacolo...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-016-9796-3
更新日期:2017-04-01 00:00:00
abstract::Following stroke, complete cellular death in the ischemic brain area may ensue, with remaining brain areas undergoing tissue remodelling to various degrees. Experience-dependent brain plasticity exerted through an enriched environment (EE) promotes remodelling after central nervous system injury, such as stroke. Post-...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-017-0461-2
更新日期:2018-03-01 00:00:00
abstract::The functions of chloride channels in preconditioning-induced cell protection remain unclear. In this report, we show that the volume-activated chloride channels play a key role in hydrogen peroxide (H2O2) preconditioning-induced cell protection in pheochromocytoma PC12 cells. The preconditioning with 100 μM H2O2 for ...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-013-8431-9
更新日期:2013-08-01 00:00:00
abstract::Long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been shown to play a critical role in the development of several malignancies. However, the potential molecular mechanism of MALAT1 in glioma remains unclear. In the present study, we found that the expression of MALAT1 wa...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-020-02165-0
更新日期:2020-10-19 00:00:00
abstract::The limited capacity for the central nervous system (CNS) to repair itself was first described over 100 years ago by Spanish neuroscientist Ramon Y. Cajal. However, the exact mechanisms underlying this failure in neuronal regeneration remain unclear and, as such, no effective therapeutics yet exist. Numerous studies h...
journal_title:Molecular neurobiology
pub_type: 杂志文章,评审
doi:10.1007/s12035-017-0433-6
更新日期:2018-03-01 00:00:00
abstract::Prenatal ethanol exposure can cause extensive apoptotic neurodegeneration throughout the developing central nervous system (CNS), which results in cognitive deficits and memory decline. However, the underlying mechanisms need further study. Single-minded 2 (Sim2), a transcriptional repressor, is reportedly involved in...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-014-8924-1
更新日期:2015-12-01 00:00:00
abstract::Smarcd1 is a component of an evolutionary conserved chromatin remodeling complex-SWI/SNF, which is involved in transcription factor recruitment, DNA replication, recombination, and repair. Suppression of the SWI/SNF complex required for cellular differentiation and gene regulation may be inducible for cell proliferati...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-020-02190-z
更新日期:2020-11-14 00:00:00
abstract::Involvement of membrane mineralocorticoid (MC) and glucocorticoid (GC) receptors in synaptic Zn2+ dynamics remains unclear. Here, we tested whether synaptic plasticity is affected by rapid intracellular Zn2+ dysregulation via membrane MC and GC receptor activation, in comparison with intracellular Ca2+ dysregulation. ...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-018-1159-9
更新日期:2019-02-01 00:00:00
abstract::CRMP1, a member of the collapsin response mediator protein family (CRMPs), was reported to regulate axon outgrowth in Sema3A signaling pathways via interactions with its co-receptor protein neuropilin-1 and plexin-As through the Fyn-cyclin-dependent kinase 5 (CDK5) cascade and the sequential phosphorylation of CRMP1 b...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-014-9049-2
更新日期:2016-03-01 00:00:00
abstract::Activated autophagy/mitophagy has been intensively observed in ischemic brain, but its roles remain controversial. Peroxynitrite (ONOO-), as a representative of reactive nitrogen species, is considered as a critical neurotoxic factor in mediating cerebral ischemia-reperfusion (I/R) injury, but its roles in autophagy/m...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-017-0859-x
更新日期:2018-08-01 00:00:00
abstract::Neurodegenerative diseases represent a heterogeneous group of disorders whose common characteristic is the progressive degeneration of neuronal structure and function. Although much knowledge has been accumulated on the pathophysiology of neurodegenerative diseases over the years, more efforts are needed to understand...
journal_title:Molecular neurobiology
pub_type: 杂志文章,评审
doi:10.1007/s12035-018-1031-y
更新日期:2018-12-01 00:00:00
abstract::Lactate is an energy substrate in adult brain especially when glucose is withdrawn or only lactate is present as main energy source. Besides, the most abundant lactate transporter in brain-monocarboxylate transporter 1 (MCT1)-was recognized recently. Despite this, MCT1 expressions in central nervous system (CNS) have ...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-016-9820-7
更新日期:2017-04-01 00:00:00