Abstract：
:Huntington's disease (HD) is one of the few neurodegenerative diseases with a known genetic cause, knowledge that has enabled the creation of animal models using genetic manipulations that aim to recapitulate HD pathology. The study of behavioral and neuropathological phenotypes of these HD models, however, has been plagued by inconsistent results across laboratories stemming from the lack of standardized husbandry and testing conditions, in addition to the intrinsic differences between the models. We have compared different HD models using standardized conditions to identify the most robust phenotypic differences, best suited for preclinical therapeutic efficacy studies. With a battery of tests of sensory-motor function, such as the open field and prepulse inhibition tests, we replicate previous results showing a strong and progressive behavioral deficit in the R6/2 line with an average of 129 CAG repeats in a mixed CBA/J and C57BL/6J background. We present the first behavioral characterization of a new model, an R6/2 line with an average of 248 CAG repeats in a pure C57BL/6J background, which also showed a progressive and robust phenotype. The BACHD in a FVB/N background showed robust and progressive behavioral phenotype, while the YAC128 full-length model on either an FVB/N or a C57BL/6J background generally showed milder deficits. Finally, the Hdh(Q111) knock-in mouse on a CD1 background showed very mild deficits. This first extensive standardized cross-characterization of several HD animal models under standardized conditions highlights several behavioral outcomes, such as hypoactivity, amenable to standardized preclinical therapeutic drug screening.
journal_name
Neurobiol Disjournal_title
Neurobiology of diseaseauthors
Menalled L,El-Khodor BF,Patry M,Suárez-Fariñas M,Orenstein SJ,Zahasky B,Leahy C,Wheeler V,Yang XW,MacDonald M,Morton AJ,Bates G,Leeds J,Park L,Howland D,Signer E,Tobin A,Brunner Ddoi
10.1016/j.nbd.2009.05.007subject
Has Abstractpub_date
2009-09-01 00:00:00pages
319-36issue
3eissn
0969-9961issn
1095-953Xpii
S0969-9961(09)00107-7journal_volume
35pub_type
杂志文章abstract：:Thermal hyperpnea, a pattern of breathing during hyperthermia that is characterized by an increase in tidal volume as well as breathing frequency, is known to lead to respiratory alkalosis. Thermal hyperpnea-induced respiratory alkalosis is linked to febrile seizures (FS). The heat-sensitive transient receptor potenti...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2018.08.004
更新日期：2018-11-01 00:00:00
abstract：:Butyrylcholinesterase (BChE) genotypes and protein (BuChE) activity, especially in combination with Apolipoprotein E4 (ApoE4), have been investigated as risk factors for developing Alzheimer disease (AD) and may be associated with the rate of progression of cognitive decline. Despite similar pathologic (e.g. amyloid d...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2009.05.014
更新日期：2009-08-01 00:00:00
abstract：:The protracted and age-dependent degeneration of dopamine (DA)-producing neurons of the Substantia nigra pars compacta (SNc) and ventral tegmental area (VTA) in the mammalian midbrain is a hallmark of human Parkinson's Disease (PD) and of certain genetic mouse models of PD, such as mice heterozygous for the homeodomai...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2015.05.015
更新日期：2015-10-01 00:00:00
abstract：:The terms "neuroacanthocytosis" (NA) and "neurodegeneration with brain iron accumulation" (NBIA) both refer to groups of genetically heterogeneous disorders, classified together due to similarities of their phenotypic or pathological findings. Even collectively, the disorders that comprise these sets are exceedingly r...
journal_title：Neurobiology of disease
pub_type： 杂志文章,评审
doi：10.1016/j.nbd.2012.03.006
更新日期：2012-06-01 00:00:00
abstract：:A novel oxime platform, the substituted phenoxyalkyl pyridinium oximes (US patent 9,227,937), was invented at Mississippi State University with an objective of discovering a brain-penetrating antidote to highly potent organophosphate anticholinesterases, such as the nerve agents. The goal was reactivation of inhibited...
journal_title：Neurobiology of disease
pub_type： 杂志文章,评审
doi：10.1016/j.nbd.2019.104487
更新日期：2020-01-01 00:00:00
abstract：:Frontotemporal dementia (FTD) is the second most common type of primary degenerative dementia. Some patients present an overlap between Alzheimer's disease (AD) and FTD both in neuropathological and clinical aspects. This may suggest a similar overlap in physiopathology, namely an involvement of mitochondrial DNA (mtD...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2003.11.004
更新日期：2004-03-01 00:00:00
abstract：:Multiple sclerosis (MS) is the prototypical inflammatory disease of the central nervous system (CNS), leading to multifocal demyelination and neurodegeneration. The etiology of this incurable disease is unknown and remains a matter of intensive research. The possibility that microbial infections, such as viruses or ba...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2018.05.022
更新日期：2018-09-01 00:00:00
abstract：:The activation of soluble guanylate cyclase by nitric oxide is increased in the frontal cortex but is reduced in the cerebellum of patients who died with liver cirrhosis. The aims of this work were to assess whether hyperammonemia is responsible for the region-selective alterations in guanylate cyclase modulation in l...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2004.12.001
更新日期：2005-06-01 00:00:00
abstract：:Experiments reported here were motivated by studies in both human epilepsy and animal models in which stunted dendritic arbors are observed. Our goal was to determine if chronic network hyperexcitability alters dendritic growth. Experiments were conducted in hippocampal slice cultures obtained from infant mice that ex...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2007.08.018
更新日期：2008-02-01 00:00:00
abstract：:Repeated head injuries are a major public health concern both for athletes, and members of the police and armed forces. There is ample experimental and clinical evidence that there is a period of enhanced vulnerability to subsequent injury following head trauma. Injuries that occur close together in time produce great...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2014.06.016
更新日期：2014-10-01 00:00:00
abstract：:The blossoming field of epitranscriptomics has recently garnered attention across many fields by findings that chemical modifications on RNA have immense biological consequences. Methylation of nucleotides in RNA, including N6-methyladenosine (m6A), 2-O-dimethyladenosine (m6Am), N1-methyladenosine (m1A), 5-methylcytos...
journal_title：Neurobiology of disease
pub_type： 杂志文章,评审
doi：10.1016/j.nbd.2020.105139
更新日期：2020-12-01 00:00:00
abstract：:We identify an essential role for the RGD (Arg-Gly-Asp tripeptide) moiety in vivo during adult peripheral neuron regenerative growth. Beyond a peripheral nerve transection there were rises in the fibronectin extracellular matrix, and striking rises in the mRNA and protein expression of integrin subunits sensitive to R...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2008.11.012
更新日期：2009-04-01 00:00:00
abstract：:Neuroprotective functions of erythropoietin (Epo) are thought to involve a heteroreceptor composed of both Epo receptor (Epo-R) and common beta chain (betac). Here, we measured the response of hippocampal Epo system components (Epo, Epo-R and betac) during neurodegenerative processes following pilocarpine-induced stat...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2006.10.009
更新日期：2007-02-01 00:00:00
abstract：:The role of endothelial nitric oxide (NO) in the cerebrovascular response to partial seizures was investigated in mice deleted for the endothelial NO synthase gene (eNOS-/-) and in their paired wild-type (WT) congeners. Local cerebral blood flow (LCBF, quantitative [14C]iodoantipyrine method) was measured 3-6 h after ...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2006.03.002
更新日期：2006-07-01 00:00:00
abstract：:Previous studies have indicated that administration of glial cell line-derived neurotrophic factor (GDNF) counteracts neuronal death after stroke. However, in these studies damage was evaluated at most a few days after the insult. Here, we have explored the long-term consequences of two routes of GDNF delivery to the ...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2003.08.002
更新日期：2003-12-01 00:00:00
abstract：:Immunization of mouse models of Alzheimer disease (AD) with amyloid-peptide (Abeta) reduces Abeta deposits and attenuates their memory and learning deficits. Recent clinical trials were halted due to meningoencephalitis, presumably induced by T cell mediated and/or Fc-mediated immune responses. Because injection of an...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2006.04.012
更新日期：2006-09-01 00:00:00
abstract：:Mutations in the gene encoding the RNA-binding protein TDP-43 cause amyotrophic lateral sclerosis (ALS), clinically and pathologically indistinguishable from the majority of 'sporadic' cases of ALS, establishing altered TDP-43 function and distribution as a primary mechanism of neurodegeneration. Transgenic mouse mode...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2018.09.024
更新日期：2019-01-01 00:00:00
abstract：:Background While significant advances have been made in uncovering the aetiology of Alzheimer's disease and related dementias at the genetic level, molecular events at the epigenetic level remain largely undefined. Emerging evidence indicates that small non-coding RNAs (sncRNAs) and their associated RNA modifications ...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2020.105058
更新日期：2020-11-01 00:00:00
abstract：:Pathological high-frequency oscillations (HFOs), specifically fast ripples (FRs, >250 Hz), are pathognomonic of an active epileptogenic zone. However, the origin of FRs remains unknown. Here we explored the correlation between FRs recorded with intraoperative pre-resection electrocorticography (ECoG) and spontaneous s...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2019.104618
更新日期：2020-02-01 00:00:00
abstract：:No single-omic approach completely elucidates the multitude of alterations taking place in Alzheimer's disease (AD). Here, we coupled transcriptomic and phosphoproteomic approaches to determine the temporal sequence of changes in mRNA, protein, and phosphopeptide expression levels from human temporal cortical samples,...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2018.12.009
更新日期：2019-04-01 00:00:00
abstract：:Frontotemporal dementia (FTD) is one of the most prevalent forms of early-onset dementia. It represents part of the FTD-Amyotrophic Lateral Sclerosis (ALS) spectrum, a continuum of genetically and pathologically overlapping disorders. FTD-causing mutations in CHMP2B, a gene encoding a core component of the heteromeric...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2020.105047
更新日期：2020-10-01 00:00:00
abstract：:Spinocerebellar Ataxia Type 1 (SCA1) is an autosomal dominant late onset neurodegenerative disease caused by an expanded polyglutamine tract in ataxin-1. Here, we compared the protective effects of overexpressing ataxin-1-like using recombinant AAVs, or reducing expression of mutant ataxin-1 using virally delivered RN...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2013.04.003
更新日期：2013-08-01 00:00:00
abstract：:Neurodegenerative diseases impose a burden on society, yet for the most part, the mechanisms underlying neuronal dysfunction and death in these disorders remain unclear despite the identification of relevant disease genes. Given the molecular conservation in neuronal signaling pathways across vertebrate and invertebra...
journal_title：Neurobiology of disease
pub_type： 杂志文章,评审
doi：10.1016/j.nbd.2010.05.012
更新日期：2010-10-01 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：: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：:Ubiquitination, a fundamental post-translational modification of intracellular proteins, is enzymatically reversed by deubiquitinase enzymes (deubiquitinases). >90 deubiquitinases have been identified. One of these enzymes, YOD1, possesses deubiquitinase activity and is similar to ovarian tumor domain-containing prote...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2018.01.006
更新日期：2018-04-01 00:00:00
abstract：:Polyglutamine neurodegenerative disorders are characterized by the expansion of a glutamine tract within the mutant disease-causing protein. Expression of the mutant protein induces a progressive loss of neuronal function and the subsequent neurodegeneration of a set of neurons characteristic to each disease. Spinocer...
journal_title：Neurobiology of disease
pub_type： 杂志文章,评审
doi：10.1006/nbdi.2000.0305
更新日期：2000-06-01 00:00:00
abstract：:Mechanisms determining characteristic age-of-onset for neurological diseases are largely unknown. Normal brain aging associates with robust and progressive transcriptome changes ("molecular aging"), but the intersection with disease pathways is mostly uncharacterized. Here, using cross-cohort microarray analysis of fo...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2010.09.016
更新日期：2011-02-01 00:00:00
abstract：:Glutamate-induced delayed calcium dysregulation (DCD) is a causal factor leading to neuronal death. The mechanism of DCD is not clear but Ca2+ influx via N-methyl-d-aspartate receptors (NMDAR) and/or the reverse plasmalemmal Na+/Ca2+ exchanger (NCXrev) could be involved in DCD. However, the extent to which NMDAR and N...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2011.12.051
更新日期：2012-04-01 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
