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Molecular Brain

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https://read.qxmd.com/read/30744651/da-jc1-improves-learning-and-memory-by-antagonizing-a%C3%AE-31-35-induced-circadian-rhythm-disorder
#1
Li Wang, Rui Zhang, Xiaohong Hou, Changtu Wang, Shuai Guo, Na Ning, Cong Sun, Yuan Yuan, Lin Li, Christian Hölscher, Xiaohui Wang
Studies have shown that a normal circadian rhythm is crucial to learning and memory. Circadian rhythm disturbances that occur at early stages of Alzheimer's disease (AD) aggravate the progression of the disease and further reduce learning and memory in AD patients. The novel, dual GLP-1R/GIPR agonist DA-JC1 has been found to exert a stronger hypoglycemic effect than a GLP-1R agonist alone and has been shown to exert neuroprotective effects. However, it is not clear whether DA-JC1 improves the Aβ31-35-induced decline in learning and memory ability by restoring disrupted circadian rhythms...
February 11, 2019: Molecular Brain
https://read.qxmd.com/read/30736837/determination-of-circuit-specific-morphological-adaptations-in-ventral-tegmental-area-dopamine-neurons-by-chronic-morphine
#2
Sarah C Simmons, Katie Wheeler, Michelle S Mazei-Robison
Chronic opiate exposure induces neuroadaptations in the mesocorticolimbic system including ventral tegmental area (VTA) dopamine (DA) neurons, whose soma size is decreased following opiate exposure. Yet it is now well documented that VTA DA neurons are heterogeneous, with notable differences between VTA DA neurons based on their projection target. Therefore, we sought to determine whether chronic morphine induced similar changes in the morphology of VTA DA neurons that project to the nucleus accumbens (NAc) and prefrontal cortex (PFC)...
February 8, 2019: Molecular Brain
https://read.qxmd.com/read/30736831/cav3-2-calcium-channel-interactions-with-the-epithelial-sodium-channel-enac
#3
Agustin Garcia-Caballero, Maria A Gandini, Shuo Huang, Lina Chen, Ivana A Souza, Yan L Dang, M Jackson Stutts, Gerald W Zamponi
This study describes the functional interaction between Cav3.2 calcium channels and the Epithelial Sodium Channel (ENaC). β-ENaC subunits showed overlapping expression with endogenous Cav3.2 calcium channels in the thalamus and hypothalamus as detected by immunostaining. Moreover, β- and γ-ENaC subunits could be co-immunoprecipitated with Cav3.2 calcium channels from brain lysates, dorsal horn and lumbar dorsal root ganglia. Mutation of a cluster of lysines present in the intracellular N-terminus region of β-ENaC (K4R/ K5R/ K9R/ K16R/ K23R) reduced interactions with Cav3...
February 8, 2019: Molecular Brain
https://read.qxmd.com/read/30736828/baicalin-regulates-the-dopamine-system-to-control-the-core-symptoms-of-adhd
#4
Rongyi Zhou, Jiaojiao Wang, Xinmin Han, Bingxiang Ma, Haixia Yuan, Yuchen Song
We aimed to test the therapeutic effects of baicalin on attention deficit hyperactivity disorder (ADHD) in an animal model and to explain the potential mechanism. We investigated the therapeutic effects and mechanisms of baicalin in a spontaneously hypertensive rat (SHR) model of ADHD depending on the dopamine (DA) deficit theory. In this study, fifty SHRs were randomly divided into five groups: methylphenidate (MPH), baicalin (50 mg/kg, 100 mg/kg, or 150 mg/kg), and saline-treated. Ten Wistar Kyoto (WKY) rats were used as controls...
February 8, 2019: Molecular Brain
https://read.qxmd.com/read/30736823/motor-skills-mediated-through-cerebellothalamic-tracts-projecting-to-the-central-lateral-nucleus
#5
Nobuyuki Sakayori, Shigeki Kato, Masateru Sugawara, Susumu Setogawa, Hotaka Fukushima, Rie Ishikawa, Satoshi Kida, Kazuto Kobayashi
The cerebellum regulates complex animal behaviors, such as motor control and spatial recognition, through communication with many other brain regions. The major targets of the cerebellar projections are the thalamic regions including the ventroanterior nucleus (VA) and ventrolateral nucleus (VL). Another thalamic target is the central lateral nucleus (CL), which receives the innervations mainly from the dentate nucleus (DN) in the cerebellum. Although previous electrophysiological studies suggest the role of the CL as the relay of cerebellar functions, the kinds of behavioral functions mediated by cerebellothalamic tracts projecting to the CL remain unknown...
February 8, 2019: Molecular Brain
https://read.qxmd.com/read/30700334/correction-to-the-effect-of-neuroligin-2-absence-on-sleep-architecture-and-electroencephalographic-activity-in-mice
#6
Bong Soo Seok, Feng Cao, Erika Bélanger-Nelson, Chloé Provost, Steve Gibbs, Zhengping Jia, Valérie Mongrain
Correction to: Molecular Brain (2018) 11:52 https://doi.org/10.1186/s13041-018-0394-3Following publication of the original article [1], the authors reported that the article was mistakenly submitted with the omission of two authors: Feng Cao and Zhengping Jia. The authors declare that this was an error made in good faith. The corrected author list and list of affiliations are used in this Correction. The changes made to the author list and list of affiliations are also listed below, as well as the revised 'Acknowledgements' section and 'Authors' contributions' section...
January 30, 2019: Molecular Brain
https://read.qxmd.com/read/30691483/genetic-risk-variants-for-brain-disorders-are-enriched-in-cortical-h3k27ac-domains
#7
Eilis Hannon, Sarah J Marzi, Leonard S Schalkwyk, Jonathan Mill
Most variants associated with complex phenotypes in genome-wide association studies (GWAS) do not directly index coding changes affecting protein structure. Instead they are hypothesized to influence gene regulation, with common variants associated with disease being enriched in regulatory domains including enhancers and regions of open chromatin. There is interest, therefore, in using epigenomic annotation data to identify the specific regulatory mechanisms involved and prioritize risk variants. We quantified lysine H3K27 acetylation (H3K27ac) - a robust mark of active enhancers and promoters that is strongly correlated with gene expression and transcription factor binding - across the genome in entorhinal cortex samples using chromatin immunoprecipitation followed by highly parallel sequencing (ChIP-seq)...
January 28, 2019: Molecular Brain
https://read.qxmd.com/read/30691479/quantitative-profiling-brain-proteomes-revealed-mitochondrial-dysfunction-in-alzheimer-s-disease
#8
Sunil S Adav, Jung Eun Park, Siu Kwan Sze
Mitochondrial dysfunction is a key feature in both aging and neurodegenerative diseases including Alzheimer's disease (AD), but the molecular signature that distinguishes pathological changes in the AD from healthy aging in the brain mitochondria remain poorly understood. In order to unveil AD specific mitochondrial dysfunctions, this study adopted a discovery-driven approach with isobaric tag for relative and absolute quantitation (iTRAQ) and label-free quantitative proteomics, and profiled the mitochondrial proteomes in human brain tissues of healthy and AD individuals...
January 28, 2019: Molecular Brain
https://read.qxmd.com/read/30683131/hyperexcitability-of-the-local-cortical-circuit-in-mouse-models-of-tuberous-sclerosis-complex
#9
Jian-Ping Zhao, Akira Yoshii
Tuberous sclerosis complex (TSC) is a neurogenetic disorder associated with epilepsy, intellectual disabilities, and autistic behaviors. These neurological symptoms result from synaptic dysregulations, which shift a balance between excitation and inhibition. To decipher the synaptic substrate of hyperexcitability, we examined pan-neuronal Tsc1 knockout mouse and found a reduction in surface expression of a GABA receptor (GABAR) subunit but not AMPA receptor (AMPAR) subunit. Using electrophysiological recordings, we found a significant reduction in the frequency of GABAR-mediated miniature inhibitory postsynaptic currents (GABAR-mIPSCs) but not AMPAR-mediated miniature excitatory postsynaptic currents (AMPAR-mEPSCs) in layer 2/3 pyramidal neurons...
January 25, 2019: Molecular Brain
https://read.qxmd.com/read/30658665/reduced-expression-of-somatostatin-in-gabaergic-interneurons-derived-from-induced-pluripotent-stem-cells-of-patients-with-parkin-mutations
#10
Chizuru Iwasawa, Naoko Kuzumaki, Yukari Suda, Reiko Kagawa, Yuko Oka, Nobutaka Hattori, Hideyuki Okano, Minoru Narita
Parkinson's disease (PD) is associated with both motor and non-motor symptoms, including constipation, sensory neuropathy, depression, dementia and sleep disorder. Somatostatin (SST) is considered to be a modulator of GABAergic inhibitory transmission, and its levels are reduced in cerebrospinal fluid of PD patients. In the present study, we evaluated the changes in the expression of SST in GABAergic neurons derived from induced pluripotent stem cells (iPSCs) of PD patients. Neural cells were co-treated with the Wnt antagonist IWP-2 and Shh during neurosphere formation to induce GABA-positive forebrain interneurons...
January 18, 2019: Molecular Brain
https://read.qxmd.com/read/30626449/pathological-changes-of-distal-motor-neurons-after-complete-spinal-cord-injury
#11
Kazuya Yokota, Kensuke Kubota, Kazu Kobayakawa, Takeyuki Saito, Masamitsu Hara, Ken Kijima, Takeshi Maeda, Hiroyuki Katoh, Yasuyuki Ohkawa, Yasuharu Nakashima, Seiji Okada
Traumatic spinal cord injury (SCI) causes serious disruption of neuronal circuits that leads to motor functional deficits. Regeneration of disrupted circuits back to their original target is necessary for the restoration of function after SCI, but the pathophysiological condition of the caudal spinal cord has not been sufficiently studied. Here we investigated the histological and biological changes in the distal part of the injured spinal cord, using a mice model of complete thoracic SCI in the chronic stage (3 months after injury)...
January 9, 2019: Molecular Brain
https://read.qxmd.com/read/30621738/artificial-association-of-memory-events-by-optogenetic-stimulation-of-hippocampal-ca3-cell-ensembles
#12
Naoya Oishi, Masanori Nomoto, Noriaki Ohkawa, Yoshito Saitoh, Yoshitake Sano, Shuhei Tsujimura, Hirofumi Nishizono, Mina Matsuo, Shin-Ichi Muramatsu, Kaoru Inokuchi
Previous gain-of-function studies using an optogenetic technique showed that manipulation of the hippocampal dentate gyrus or CA1 cell ensembles is important for memory reactivation and to generate synthetic or false memory. However, gain-of-function study manipulating CA3 cell ensembles has not been reported. The CA3 area of the hippocampus comprises a recurrent excitatory circuit, which is thought to be important for the generation of associations among the stored information within one brain region. We investigated whether the coincident firing of cell ensembles in one brain region, hippocampal CA3, associates distinct events...
January 8, 2019: Molecular Brain
https://read.qxmd.com/read/30621732/effects-of-rapamycin-on-social-interaction-deficits-and-gene-expression-in-mice-exposed-to-valproic-acid-in-utero
#13
Hiroko Kotajima-Murakami, Toshiyuki Kobayashi, Hirofumi Kashii, Atsushi Sato, Yoko Hagino, Miho Tanaka, Yasumasa Nishito, Yukio Takamatsu, Shigeo Uchino, Kazutaka Ikeda
The mammalian target of rapamycin (mTOR) signaling pathway plays a crucial role in cell metabolism, growth, and proliferation. The overactivation of mTOR has been implicated in the pathogenesis of syndromic autism spectrum disorder (ASD), such as tuberous sclerosis complex (TSC). Treatment with the mTOR inhibitor rapamycin improved social interaction deficits in mouse models of TSC. Prenatal exposure to valproic acid (VPA) increases the incidence of ASD. Rodent pups that are exposed to VPA in utero have been used as an animal model of ASD...
January 8, 2019: Molecular Brain
https://read.qxmd.com/read/30606245/the-peacefulness-gene-promotes-aggression-in-drosophila
#14
Mahmoudreza Ramin, Yueyang Li, Wen-Tzu Chang, Hunter Shaw, Yong Rao
Natural aggressiveness is commonly observed in all animal species, and is displayed frequently when animals compete for food, territory and mating. Aggression is an innate behaviour, and is influenced by both environmental and genetic factors. However, the genetics of aggression remains largely unclear. In this study, we identify the peacefulness (pfs) gene as a novel player in the control of male-male aggression in Drosophila. Mutations in pfs decreased intermale aggressiveness, but did not affect locomotor activity, olfactory avoidance response and sexual behaviours...
January 3, 2019: Molecular Brain
https://read.qxmd.com/read/30593289/what-does-ltp-tell-us-about-the-roles-of-camkii-and-pkm%C3%AE-in-memory
#15
LETTER
Todd Charlton Sacktor, André Antonio Fenton
In "Criteria for identifying the molecular basis of the engram (CaMKII, PKMζ)," Lisman proposes that elucidating the mechanism of LTP maintenance is key to understanding memory storage. He suggests three criteria for a maintenance mechanism to evaluate data on CaMKII and PKMζ as memory storage molecules: necessity, occlusion, and erasure. Here we show that when the criteria are tested, the results reveal important differences between the molecules. Inhibiting PKMζ reverses established, protein synthesis-dependent late-LTP, without affecting early-LTP or baseline synaptic transmission...
December 28, 2018: Molecular Brain
https://read.qxmd.com/read/30593282/in-memoriam-john-lisman-commentaries-on-camkii-as-a-memory-molecule
#16
LETTER
Mark F Bear, Sam F Cooke, Karl Peter Giese, Bong-Kiun Kaang, Mary B Kennedy, Ji-Il Kim, Richard G M Morris, Pojeong Park
Shortly before he died in October 2017, John Lisman submitted an invited review to Molecular Brain on 'Criteria for identifying the molecular basis of the engram (CaMKII, PKMζ)'. John had no opportunity to read the referees' comments, and as a mark of the regard in which he was held by the neuroscience community the Editors decided to publish his review as submitted. This obituary takes the form of a series of commentaries on Lisman's review. At the same time we are publishing as a separate article a longer response by Todd Sacktor and André Fenton entitled 'What does LTP tell us about the roles of CaMKII and PKMζ in memory?' which presents the case for a rival memory molecule, PKMζ...
December 28, 2018: Molecular Brain
https://read.qxmd.com/read/30563578/erib-targeted-inhibition-of-microglia-activity-attenuates-mpp-induced-da-neuron-injury-through-the-nf-%C3%AE%C2%BAb-signaling-pathway
#17
Fangfang Dou, Xinkun Chu, Bei Zhang, Liang Liang, Guoqiang Lu, Jianqing Ding, Shengdi Chen
Accumulating evidence indicates that microglia activation is associated with an increased risk for developing Parkinson's disease (PD). With the progressive and selective degeneration of dopaminergic (DA) neurons, proinflammatory cytokines are elevated in the substantia nigra (SN) of PD patients. Thus, anti-inflammation has become one of the therapeutic strategies of PD. Eriocalyxin B (EriB), a diterpenoid isolated from Isodoneriocalyx, was previously reported to have anti-inflammatory effects. MPTP mouse model and MPP+ cell model were prepared to detect the role of EriB in regulating microglia activation and neuron protection...
December 18, 2018: Molecular Brain
https://read.qxmd.com/read/30563553/hyperpolarized-1-13c-pyruvate-mr-spectroscopy-detect-altered-glycolysis-in-the-brain-of-a-cognitively-impaired-mouse-model-fed-high-fat-diet
#18
Young-Suk Choi, Somang Kang, Sang-Yoon Ko, Saeram Lee, Jae Young Kim, Hansol Lee, Jae Eun Song, Dong-Hyun Kim, Eosu Kim, Chul Hoon Kim, Lisa Saksida, Ho-Taek Song, Jong Eun Lee
Higher dietary intakes of saturated fatty acid increase the risk of developing Alzheimer's disease and dementia, and even in people without diabetes higher glucose levels may be a risk factor for dementia. The mechanisms causing neuronal dysfunction and dementia by consuming high-fat diet degrading the integrity of the blood-brain barrier (BBB) has been suggested but are not yet fully understood, and metabolic state of the brain by this type of insult is still veiled. The objective of this study was to investigate the effect of high-fat diet on the brain metabolism by a multimodal imaging method using the hyperpolarizedcarbon 13 (13 C)-pyruvate magnetic resonance (MR) spectroscopy and dynamic contrast-enhanced MR imaging in conjunction with the biochemical assay and the behavior test in a mouse model fed high-fat diet (HFD)...
December 18, 2018: Molecular Brain
https://read.qxmd.com/read/30558654/systemic-functional-enrichment-and-cerna-network-identification-following-peripheral-nerve-injury
#19
Tianmei Qian, Chunlin Fan, Qianyan Liu, Sheng Yi
Peripheral nerve injury is a worldwide clinical issue that impacts patients' quality of life and causes huge society and economic burden. Injured peripheral nerves are able to regenerate by themselves. However, for severe peripheral nerve injury, the regenerative abilities are very limited and the regenerative effects are very poor. A better understanding of the mechanisms following peripheral nerve injury will benefit its clinical treatment. In this study, we systematically explored the dynamic changes of mRNAs and long non-coding RNAs (lncRNAs) in the injured sciatic nerve segments after nerve crush, identified significantly involved Gene ontology (GO) terms and Kyoto Enrichment of Genes and Genomes (KEGG) pathways, and innovatively analyzed the correlation of differentially expressed mRNAs and lncRNAs...
December 17, 2018: Molecular Brain
https://read.qxmd.com/read/30514335/dual-roles-of-anterior-cingulate-cortex-neurons-in-pain-and-pleasure-in-adult-mice
#20
Jing-Shan Lu, Qi-Yu Chen, Sibo Zhou, Kaoru Inokuchi, Min Zhuo
Human and animal studies indicate that some brain regions are activated during painful and pleasant situations, such as the anterior cingulate cortex (ACC). In the present study, we wanted to determine if some of the same neurons in the ACC may be activated by both pain and pleasure. We labeled neurons activated by two stimuli by using two immediate early genes (IEGs), Arc and Homer1a, and detected the intranuclear transcription of the IEG mRNA in situ. We found that there are double-labeling neurons in the ACC after the mice received pain and sexual attraction stimulation...
December 4, 2018: Molecular Brain
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