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Molecular Brain

Vinicius M Gadotti, Gerald W Zamponi
Cav3.2 T-type calcium channels are important for the signaling of nociceptive information in the primary afferent pain pathway. During neuropathy and peripheral inflammation, Cav3.2 channels are upregulated due to an increased association with the deubiquitinase USP5. Disrupting these interactions in male mice by the use of cell permeant peptides reverses mechanical and thermal hypersensitivity. Here we explore the effects of interfering with USP5 binding to the channel in female mice with synchronized estrous cycle...
October 19, 2018: Molecular Brain
Jing Liu, Lili Tong, Shuangshuang Song, Yue Niu, Jun Li, Xiu Wu, Jie Zhang, Clement C Zai, Fang Luo, Jian Wu, Haiyin Li, Albert H C Wong, Ruopeng Sun, Fang Liu, Baomin Li
Following publication of the original article [1], the authors reported that one of the authors' names is spelled incorrectly.
October 16, 2018: Molecular Brain
Chunmei Jin, Yinhua Zhang, Shinhyun Kim, Yoonhee Kim, Yeunkum Lee, Kihoon Han
The SH3 and multiple ankyrin repeat domains 3 (SHANK3) gene encodes core scaffolds in neuronal excitatory postsynapses. SHANK3 duplications have been identified in patients with hyperkinetic disorders and early-onset generalized tonic-clonic seizures. Consistently, Shank3 transgenic (TG) mice, which mildly overexpress Shank3 proteins exhibit hyperkinetic behavior and spontaneous seizures. However, the seizure phenotype of Shank3 TG mice has only been investigated in adults of the seizure-sensitive strain FVB/N...
October 10, 2018: Molecular Brain
Ruixia Zhu, Xu Liu, Zhiyi He
Objectives Long non-coding RNAs (lncRNAs) have been identified as key regulators in the development of atherosclerosis, which is a major cause of ischemic stroke. However, to date, there are no reports on the association between lncRNA gene variation and the risk of ischemic stroke. Therefore, we assessed the association between H19 and MALAT1 gene polymorphisms and susceptibility to ischemic stroke in a northern Chinese Han population. Methods In our study, we genotyped four genetic variations in lncRNA-H19 and -MALAT1 (rs217727, rs2251375, rs619586, and rs3200401) in a case-control study of 567 ischemic stroke patients and 552 control subjects...
October 10, 2018: Molecular Brain
Katsunori Kobayashi, Tsuyoshi Takagi, Shunsuke Ishii, Hidenori Suzuki, Tsuyoshi Miyakawa
The dentate gyrus of the hippocampus has been implicated in the pathophysiological basis of neuropsychiatric disorders including schizophrenia. We have identified several mouse models of neuropsychiatric disorders with robust molecular and functional defects in the dentate gyrus. Among them, mice lacking Schnurri-2 (Shn2 or HIVEP2) have been proposed as a model of schizophrenia and intellectual disability. Shn2 knockout mice exhibit behavioral abnormalities resembling symptoms of schizophrenia and HIVEP2-related intellectual disability as well as marked functional alterations in the soma and output synapse of the dentate granule cells (GCs)...
October 1, 2018: Molecular Brain
Tzu-Hao Harry Chao, Jyh-Horng Chen, Chen-Tung Yen
Neuropathic pain is a major worldwide health problem. Although central sensitization has been reported in well-established neuropathic conditions, information on the acute brain activation patterns in response to peripheral nerve injury is lacking. This study first mapped the brain activity in rats immediately following spared nerve injury (SNI) of the sciatic nerve. Using blood-oxygenation-level-dependent functional magnetic resonance imaging (BOLD-fMRI), we observed sustained activation in the bilateral insular cortices (ICs), primary somatosensory cortex (S1), and cingulate cortex...
October 1, 2018: Molecular Brain
Shuang Qiu, Yu Wu, Xinyou Lv, Xia Li, Min Zhuo, Kohei Koga
Fragile X syndrome is caused by the loss of fragile X mental retardation protein (FMRP). Kainate receptor (KAR) is a subfamily of ionotropic glutamate receptors (iGluR) that acts mainly as a neuromodulator of synaptic transmission and neuronal excitability. However, little is known about the changes of synaptic KAR in the cortical area of Fmr1 KO mice. In this study, we performed whole-cell patch-clamp recordings from layer II/III pyramidal neurons in the insular cortex of Fmr1 KO mice. We found that KARs mediated currents were reduced in Fmr1 KO mice...
September 21, 2018: Molecular Brain
Karen M Jiménez, Angela J Pereira-Morales, Ana Adan, Sandra Lopez-Leon, Diego A Forero
Genetic studies of major depressive disorder and its associated endophenotypes are useful for the identification of candidate genes. In recent years, variations in non-coding RNA genes, such as miRNAs, have been explored as novel candidates for psychiatric disorders and related endophenotypes. The aim of the present study was to evaluate the possible association between a functional polymorphism (rs12720208) in the FGF20 gene, which regulates its modulation by miR-433, and depressive symptoms in young adults...
September 21, 2018: Molecular Brain
Bong Soo Seok, Erika Bélanger-Nelson, Chloé Provost, Steve Gibbs, Valérie Mongrain
Sleep disorders are comorbid with most psychiatric disorders, but the link between these is not well understood. Neuroligin-2 (NLGN2) is a cell adhesion molecule that plays roles in synapse formation and neurotransmission. Moreover, NLGN2 has been associated with psychiatric disorders, but its implication in sleep remains underexplored. In the present study, the effect of Nlgn2 knockout (Nlgn2-/- ) on sleep architecture and electroencephalographic (EEG) activity in mice has been investigated. The EEG and electromyogram (EMG) were recorded in Nlgn2-/- mice and littermates for 24 h from which three vigilance states (i...
September 19, 2018: Molecular Brain
María Rodríguez-Muñoz, Yara Onetti, Elsa Cortés-Montero, Javier Garzón, Pilar Sánchez-Blázquez
Cannabidiol (CBD), the major non-psychotomimetic compound present in the Cannabis sativa plant, exhibits therapeutic potential for various human diseases, including chronic neurodegenerative diseases, such as Alzheimer's and Parkinson's, ischemic stroke, epilepsy and other convulsive syndromes, neuropsychiatric disorders, neuropathic allodynia and certain types of cancer. CBD does not bind directly to endocannabinoid receptors 1 and 2, and despite research efforts, its specific targets remain to be fully identified...
September 17, 2018: Molecular Brain
Huazheng Liang, Hongqin Wang, Shaoshi Wang, Richard Francis, George Paxinos, Xufeng Huang
AIMS: Postsynaptic density - 95 kDa protein (PSD95) is an important molecule on the postsynaptic membrane. It interacts with many other proteins and plays a pivotal role in learning and memory formation. Its distribution in the brain has been studied previously using in situ hybridization as well as immunohistochemistry. However, these studies are based on 2 dimensional (2D) sections and results are presented with a few sections. The present study aims to show PSD-95 distribution in 3 dimensions (3D) without slicing the brain tissue of C57BL/6 mice into sections using the advanced CUBIC technique...
September 12, 2018: Molecular Brain
Hyopil Kim, Hyun-Seok Kim, Bong-Kiun Kaang
A class of NAD-dependent protein deacetylases, the Sirtuin (SIRT) family of proteins is involved in aging, cell survival, and neurodegeneration. Recently, SIRT proteins, including SIRT6, have been reported to be important in learning and memory. However, the role of SIRT6 in excitatory brain neurons in cognitive behaviors is not well characterized. We investigated how cognitive behaviors are affected by genetic SIRT6 depletion in excitatory neurons in the mouse forebrain. We generated a conditional knockout (cKO) mouse line by mating two transgenic lines, Floxed SIRT6 and CaMKIIa-Cre...
September 6, 2018: Molecular Brain
Jing Liu, Lili Tong, Shuangshuang Song, Yue Niu, Jun Li, Xiu Wu, Jie Zhang, Clement C Zai, Fang Luo, Jian Wu, Haiyin Li, Albert H C Wong, Ruopeng Sun, Fang Liu, Baomin Li
Pediatric refractory epilepsy is a broad phenotypic spectrum with great genetic heterogeneity. Next-generation sequencing (NGS) combined with Sanger sequencing could help to understand the genetic diversity and underlying disease mechanisms in pediatric epilepsy. Here, we report sequencing results from a cohort of 172 refractory epilepsy patients aged 0-14 years. The pathogenicity of identified variants was evaluated in accordance with the American College of Medical Genetics and Genomics (ACMG) criteria. We identified 43 pathogenic or likely pathogenic variants in 40 patients (23...
September 5, 2018: Molecular Brain
Jie-Min Jia, Chuanqi Peng, Yihui Wang, Jie Zheng, Woo-Ping Ge
Ischemic perinatal stroke (IPS) is common, resulting in significant mortality and morbidity. In such cases, the incidence of unilateral arterial cerebral infarction is often occluded in the middle cerebral artery (MCA), leading to focal ischemia. In adult rodents, blockage of MCA is the most frequently used strategy for ischemic stroke study. However, modeling MCA occlusion (MCAo) in postnatal day 0-7 (P0-7) mouse pups for IPS study has not been accomplished. Here we occluded the dMCA by inducing the accumulation of magnetic particles (MPs) administered through the superficial temporal vein of mice between P0 and P7, which we called neonatal or perinatal SIMPLE (Stroke Induced with Magnetic Particles)...
August 29, 2018: Molecular Brain
Shamprasad Varija Raghu, Farhan Mohammad, Jia Yi Chua, Joanne Shi Woon Lam, Mavis Loberas, Sadhna Sahani, Claudia S Barros, Adam Claridge-Chang
The analysis of behavior requires that the underlying neuronal circuits are identified and genetically isolated. In several major model species-most notably Drosophila-neurogeneticists identify and isolate neural circuits with a binary heterologous expression-control system: Gal4-UASG. One limitation of Gal4-UASG is that expression patterns are often too broad to map circuits precisely. To help refine the range of Gal4 lines, we developed an intersectional genetic AND operator. Interoperable with Gal4, the new system's key component is a fusion protein in which the DNA-binding domain of Gal4 has been replaced with a zinc finger domain with a different DNA-binding specificity...
August 20, 2018: Molecular Brain
Bhagirathi Dash, Sulayman D Dib-Hajj, Stephen G Waxman
The alpha1 (α1) subunit of the sodium/potassium ATPase (i.e., Na+ /K+ -ATPase α1), the prototypical sodium pump, is expressed in each eukaryotic cell. They pump out three sodium ions in exchange for two extracellular potassium ions to establish a cellular electrochemical gradient important for firing of neuronal and cardiac action potentials. We hypothesized that myosin (myo or myh) motor proteins might interact with Na+ /K+ -ATPase α1 subunits in order for them to play an important role in the transport and trafficking of sodium pump...
August 7, 2018: Molecular Brain
Jung-Hwa Tao-Cheng
Neurons exhibit stimulation-induced ultrastructural changes such as increase of thickness and curvature of the postsynaptic density, decrease in contact area between subsurface cistern and plasma membrane, and formation of CaMKII clusters and synaptic spinules. These structural characteristics help in identifying the activity state of the neuron and should be taken into consideration when interpreting ultrastructural features of the neurons. Here in organotypic hippocampal slice cultures where experimental conditions can be easily manipulated, two additional features are documented in forebrain neurons as reliable benchmarks for stimulation-induced structural changes: (1) The neuronal nucleus showed conspicuous clustering of dark chromatin, and (2) the endoplasmic reticulum formed stacks with a uniform gap of ~ 13 nm filled with dark materials...
July 27, 2018: Molecular Brain
Danae Campos-Melo, Zachary C E Hawley, Michael J Strong
Neurofilaments (NFs) are the most abundant cytoskeletal component of vertebrate myelinated axons. NFs function by determining axonal caliber, promoting axonal growth and forming a 3-dimensional lattice that supports the organization of cytoplasmic organelles. The stoichiometry of NF protein subunits (NFL, NFM and NFH) has to be tightly controlled to avoid the formation of NF neuronal cytoplasmic inclusions (NCIs), axonal degeneration and neuronal death, all pathological hallmarks of amyotrophic lateral sclerosis (ALS)...
July 20, 2018: Molecular Brain
Hirotaka Shoji, Tsuyoshi Miyakawa
Prepulse inhibition (PPI) is the suppression of a startle reflex response to a startle stimulus that occurs when a weak prepulse stimulus precedes the startle stimulus. PPI is measured to assess sensorimotor gating across species, including humans and rodents. Reduced PPI, which is thought to reflect dysfunction of sensorimotor gating, is reported in patients with psychiatric disorders, such as schizophrenia, bipolar disorder, and post-traumatic stress disorder (PTSD), and in animal models of these disorders...
July 13, 2018: Molecular Brain
Beatrice Bianchi, Paul A Smith, Hugues Abriel
Transient receptor potential melastatin member 4 (TRPM4), a Ca2+ -activated nonselective cation channel, has been found to mediate cell membrane depolarization in immune response, insulin secretion, cardiovascular diseases, and cancer. In murine experimental autoimmune encephalomyelitis (EAE), TRPM4 deletion and administration of glibenclamide were found to ameliorate clinical symptoms and attenuate disease progression. However, the exact role of TRPM4 in EAE, as well as the molecular mechanisms underlining TRPM4 contribution in EAE, remain largely unclear...
July 11, 2018: Molecular Brain
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