Abstract：
:A wide spectrum of focal, regional, or diffuse structural brain abnormalities, collectively known as malformations of cortical development (MCDs), frequently manifest with intellectual disability (ID), epilepsy, and/or autistic spectrum disorder (ASD). As the acronym suggests, MCDs are perturbations of the normal architecture of the cerebral cortex and hippocampus. The pathogenesis of these disorders remains incompletely understood; however, one area that has provided important insights has been the study of neuronal migration. The amalgamation of human genetics and experimental studies in animal models has led to the recognition that common genetic causes of neurodevelopmental disorders, including many severe epilepsy syndromes, are due to mutations in genes regulating the migration of newly born post-mitotic neurons. Neuronal migration genes often, though not exclusively, code for proteins involved in the function of the cytoskeleton. Other cellular processes, such as cell division and axon/dendrite formation, which similarly depend on cytoskeletal functions, may also be affected. We focus here on how the susceptibility of the highly organized neocortex and hippocampus may be due to their laminar organization, which involves the tight regulation, both temporally and spatially, of gene expression, specialized progenitor cells, the migration of neurons over large distances and a birthdate-specific layering of neurons. Perturbations in neuronal migration result in abnormal lamination, neuronal differentiation defects, abnormal cellular morphology and circuit formation. Ultimately this results in disorganized excitatory and inhibitory activity leading to the symptoms observed in individuals with these disorders.
journal_name
Neurobiol Disjournal_title
Neurobiology of diseaseauthors
Stouffer MA,Golden JA,Francis Fdoi
10.1016/j.nbd.2015.08.003subject
Has Abstractpub_date
2016-08-01 00:00:00pages
18-45issue
Pt Aeissn
0969-9961issn
1095-953Xpii
S0969-9961(15)30024-3journal_volume
92pub_type
杂志文章,评审abstract：:All tauopathies result in various forms of cognitive decline and neuronal loss. Although in some diseases, tau mutations appear to cause neurodegeneration, the toxic "form" of tau remains elusive. Tau is the major protein found within neurofibrillary tangles (NFTs) and therefore it seemed rational to assume that aggre...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2014.03.002
更新日期：2014-07-01 00:00:00
abstract：:Constitutive expression of C-C chemokine receptor (CCR) 5 has been detected in astrocytes, microglia and neurons, but its physiological roles in the central nervous system are obscure. The bidirectional interactions between neuron and glial cells through CCR5 and its ligands were thought to be crucial for maintaining ...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2012.08.001
更新日期：2013-01-01 00:00:00
abstract：BACKGROUND:Traumatic brain injury (TBI) causes 10-20% of acquired epilepsy, which typically develops within 2 years post-injury with poorly understood mechanisms. We investigated the location, severity, evolution and persistence of blood-brain barrier (BBB) dysfunction and associated neuroinflammation after TBI, and th...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2020.105080
更新日期：2020-11-01 00:00:00
abstract：:Neuropeptide Y (NPY) and NPY receptors are widely expressed in the mammalian central nervous system. Studies in both humans and rodent models revealed that brain NPY levels are altered in some neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease, Huntington's disease and Machado-Joseph disease...
journal_title：Neurobiology of disease
pub_type： 杂志文章,评审
doi：10.1016/j.nbd.2016.07.022
更新日期：2016-11-01 00:00:00
abstract：:Human apolipoprotein E (apoE) exists in three isoforms: apoE2, apoE3 and apoE4. APOE ε4 is a major genetic risk factor for cardiovascular disease (CVD) and Alzheimer's disease (AD). ApoE mediates cholesterol metabolism by binding various receptors. The low-density lipoprotein receptor (LDLR) has a high affinity for ap...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2013.12.016
更新日期：2014-04-01 00:00:00
abstract：:Frontotemporal dementia (FTD) is typified by behavioral and cognitive changes manifested as altered social comportment and impaired memory performance. To investigate the neurodegenerative consequences of progranulin gene (GRN) mutations, which cause an inherited form of FTD, we used previously generated progranulin k...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2011.08.029
更新日期：2012-01-01 00:00:00
abstract：:Deregulation of intracellular calcium homeostasis is widely considered as one of the underlying pathophysiological mechanisms of hypoxic-ischemic brain injury. Whether this alteration can result in cerebral calcification was investigated in basal ganglia, cerebral cortex, and hippocampus of human premature and term ne...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1006/nbdi.2000.0332
更新日期：2001-02-01 00:00:00
abstract：:Freezing of gait (FOG) is a devastating axial motor symptom in Parkinson's disease (PD) leading to falls, institutionalization, and even death. The response of FOG to dopaminergic medication and deep brain stimulation (DBS) is complex, variable, and yet to be optimized. Fundamental gaps in the knowledge of the underly...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2018.09.004
更新日期：2018-12-01 00:00:00
abstract：:Huntington disease (HD) is an adult onset, neurodegenerative disorder that results from CAG expansion in the HD gene. Recent work has demonstrated testicular degeneration in mouse models of HD and alterations in the hypothalamic-pituitary-gonadal (HPG) axis in HD patients. Here, we show that HD patients have specific ...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2007.01.006
更新日期：2007-06-01 00:00:00
abstract：:It is widely accepted that the angiotensin AT2-receptor (AT2R) has neuroprotective features. In the present study we tested pharmacological AT2R-stimulation as a therapeutic approach in a model of spinal cord compression injury (SCI) in mice using the novel non-peptide AT2R-agonist, Compound 21 (C21). Complementary ex...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2012.11.008
更新日期：2013-03-01 00:00:00
abstract：:The optic nerve crush injury is a well-accepted model to study the mechanisms of axonal regeneration after trauma in the CNS. The infection of retinal ganglion cells (RGCs) with an adeno-associated virus serotype 2 - ciliary neurotrophic factor (AAV2.CNTF) was previously shown to stimulate axonal regeneration. However...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2012.11.011
更新日期：2013-03-01 00:00:00
abstract：:The unfolded protein response (UPR) monitors the folding environment within the endoplasmic reticulum (ER). Accumulation of misfolded proteins within the ER activates the UPR resulting in the execution of adaptive or non-adaptive signaling pathways. α-Synuclein (α-syn) whose accumulation and aggregation define the pat...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2015.02.005
更新日期：2015-04-01 00:00:00
abstract：:The developing rodent brain is vulnerable to pharmacological blockade of N-methyl-d-aspartate (NMDA) receptors which can lead to severe and disseminated apoptotic neurodegeneration. Here, we show that systemic administration of the NMDA receptor antagonist MK801 to 7-day-old rats leads to impaired activity of extracel...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2004.03.013
更新日期：2004-07-01 00:00:00
abstract：:Neurofibrillary degeneration in transgenic models of tauopathies has been observed to be enhanced when these models are crossed with transgenic models developing an Aβ pathology. The mechanisms leading to this enhanced tau pathology are not well understood. We have performed a detailed analysis of tau misprocessing in...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2013.09.010
更新日期：2014-02-01 00:00:00
abstract：:Taking advantage of a progressive nonhuman primate model mimicking Parkinson's disease (PD) evolution, we monitored transcriptional fluctuations in the substantia nigra using Affymetrix microarrays in control (normal), saline-treated (normal), 6 days-treated (asymptomatic with 20% cell loss), 12 days-treated (asymptom...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2005.02.005
更新日期：2005-10-01 00:00:00
abstract：:Extracellular nucleotides exert a variety of biological actions through different subtypes of P2 receptors. Here we characterized in the human neuroblastoma SH-SY5Y cells the simultaneous presence of various P2 receptors, belonging to the P2X ionotropic and P2Y metabotropic families. Western blot analysis detected the...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2004.09.001
更新日期：2005-02-01 00:00:00
abstract：:Altered expression and distribution of neurotransmitter receptors, including metabotropic glutamate receptors (mGluRs), constitute key aspects in epileptogenesis, impaired hippocampal excitability and neuronal degeneration. mGluR1 mediates predominantly excitatory effects, whereas mGluR4 acts as inhibitory presynaptic...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2007.03.003
更新日期：2007-06-01 00:00:00
abstract：:Acoustically evoked seizures (e.g., audiogenic seizures or AGS) are common in models of inherited epilepsy and occur in a variety of species including rat, mouse, and hamster. Two models that have been particularly well studied are the genetically epilepsy prone rat (GEPR-3) and the Wistar Audiogenic Rat (WAR) strains...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2017.12.014
更新日期：2018-03-01 00:00:00
abstract：:Males and females show a different predisposition to certain types of seizures in clinical studies. Animal studies have provided growing evidence for sexual dimorphism of certain brain regions, including those that control seizures. Seizures are modulated by networks involving subcortical structures, including thalamu...
journal_title：Neurobiology of disease
pub_type： 杂志文章,评审
doi：10.1016/j.nbd.2014.05.010
更新日期：2014-12-01 00:00:00
abstract：:Failure of cell cycle regulation in neurons might be critically involved in the process of neurodegeneration in Alzheimer's disease (AD). We present here evidence to support the hypothesis that cell cycle alterations occur in cells other than neurons in AD sufferers. Lymphocytes from AD patients immortalized with Epst...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/s0969-9961(03)00040-8
更新日期：2003-08-01 00:00:00
abstract：:Rare de novo mutations in genes associated with inherited Mendelian disorders are potential contributors to sporadic disease. DYT1 dystonia is an autosomal dominant, early-onset, generalized dystonia associated with an in-frame, trinucleotide deletion (n. delGAG, p. ΔE 302/303) in the Tor1a gene. Here we examine the s...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2016.05.003
更新日期：2016-09-01 00:00:00
abstract：:Spinocerebellar ataxia type 3 (SCA3) or Machado-Joseph disease (MJD) belongs to a group of autosomal dominant neurodegenerative diseases, which are caused by the expansion of a polyglutamine repeat in the affected protein, in this case ataxin-3. Ataxin-3 is mainly localized in the cytoplasm; however, one hallmark of S...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2009.07.020
更新日期：2009-11-01 00:00:00
abstract：:CLN5 disease, late infantile variant phenotype neuronal ceroid lipofuscinosis, is a severe neurodegenerative disease caused by mutations in the CLN5 gene, which encodes a lysosomal protein of unknown function. Cln5-deficiency in mice leads to loss of thalamocortical neurons, and glial activation, but the underlying me...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2011.12.009
更新日期：2012-04-01 00:00:00
abstract：:The autophagy-lysosomal degradation pathway plays a role in the onset and progression of neurodegenerative diseases. Clinical and genetic studies indicate that mutations of beta-glucocerebrosidase represent genetic risk factors for synucleinopathies, including Parkinson's Disease (PD) and Dementia with Lewy Bodies (DL...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2009.03.002
更新日期：2009-06-01 00:00:00
abstract：:The pathophysiology of Parkinson's disease (PD) and of L-DOPA-induced dyskinesia (LID) is associated with dysfunctional neuronal activity in several nuclei of the basal ganglia. Moreover, high levels of oscillatory activity and synchronization have also been described in both intra- and inter-basal ganglia nuclei and ...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2016.02.003
更新日期：2016-05-01 00:00:00
abstract：:Aging is the strongest risk factor for metabolic, vascular and neurodegenerative diseases. Aging alone is associated with a gradual decline of cognitive and motor functions. Considering an increasing elderly population in the last century, understanding the cellular and molecular mechanisms contributing to brain aging...
journal_title：Neurobiology of disease
pub_type： 杂志文章,评审
doi：10.1016/j.nbd.2020.105008
更新日期：2020-09-01 00:00:00
abstract：:The inwardly-rectifying potassium channel Kir4.1 is a major player in the astrocyte-mediated regulation of [K(+)](o) in the brain, which is essential for normal neuronal activity and synaptic functioning. KCNJ10, encoding Kir4.1, has been recently linked to seizure susceptibility in humans and mice, and is a possible ...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2011.03.016
更新日期：2011-07-01 00:00:00
abstract：:Major depressive disorder (MDD) is one of the most prevalent major psychiatric disorders with a lifetime prevalence of 17%. Recent evidence suggests MDD is not only a brain dysfunction, but a systemic disease affecting the whole body. Central and peripheral inflammatory changes seem to be a centerpiece of MDD patholog...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2016.01.015
更新日期：2016-05-01 00:00:00
abstract：:Schizophrenia is a devastating neurodevelopmental disorder that affects approximately 1% of the population. Reduced expression of the 67-kDa protein isoform of glutamic acid decarboxylase (GAD67) is a hallmark of the disease and is encoded by the GAD1 gene. In schizophrenia, GAD67 downregulation occurs in multiple int...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2013.11.001
更新日期：2014-03-01 00:00:00
abstract：:In this review, we highlight critical unresolved questions in the etiology and mechanisms causing preterm brain injury. Involvement of neurons, glia, endogenous factors and exogenous exposures is considered. The structural and functional correlates of interrupted development and injury in the premature brain are under...
journal_title：Neurobiology of disease
pub_type： 杂志文章,评审
doi：10.1016/j.nbd.2015.10.012
更新日期：2016-08-01 00:00:00
