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Molecular Brain

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https://www.readbyqxmd.com/read/29458391/down-regulation-of-ghrelin-receptors-on-dopaminergic-neurons-in-the-substantia-nigra-contributes-to-parkinson-s-disease-like-motor-dysfunction
#1
Yukari Suda, Naoko Kuzumaki, Takefumi Sone, Michiko Narita, Kenichi Tanaka, Yusuke Hamada, Chizuru Iwasawa, Masahiro Shibasaki, Aya Maekawa, Miri Matsuo, Wado Akamatsu, Nobutaka Hattori, Hideyuki Okano, Minoru Narita
Ghrelin exerts a wide range of physiological actions throughout the body and appears to be a promising target for disease therapy. Endogenous ghrelin receptors (GHSRs) are present in extrahypothalamic sites including the substantia nigra pars compacta (SNc), which is related to phenotypic dysregulation or frank degeneration in Parkinson's disease (PD). Here we found a dramatic decrease in the expression of GHSR in PD-specific induced pluripotent stem cell (iPSC)-derived dopaminergic (DAnergic) neurons generated from patients carrying parkin gene (PARK2) mutations compared to those from healthy controls...
February 20, 2018: Molecular Brain
https://www.readbyqxmd.com/read/29439730/resolvin-d2-protects-against-cerebral-ischemia-reperfusion-injury-in-rats
#2
Gang Zuo, Dongping Zhang, Rutao Mu, Haitao Shen, Xiang Li, Zhong Wang, Haiying Li, Gang Chen
Cerebral ischemia/reperfusion (I/R) injury is a critical factor leading to a poor prognosis for ischemic stroke patients. ω-3 fatty acid supplements taken as part of a daily diet have been shown to improve the prognosis of patients with ischemic stroke. In this study, we aimed to investigate the potential effects of resolvin D2 (RvD2), a derivative of ω-3 fatty acids, and its possible advantage on cerebral I/R injury in rats. Cerebral I/R caused by middle cerebral artery occlusion and reperfusion (MCAO/R) was established in Sprague-Dawley rats...
February 13, 2018: Molecular Brain
https://www.readbyqxmd.com/read/29426354/lentivirus-mediated-expression-of-human-secreted-amyloid-precursor-protein-alpha-prevents-development-of-memory-and-plasticity-deficits-in-a-mouse-model-of-alzheimer-s-disease
#3
Valerie T Y Tan, Bruce G Mockett, Shane M Ohline, Karen D Parfitt, Hollie E Wicky, Katie Peppercorn, Lucia Schoderboeck, Mohamad Fairuz Bin Yahaya, Warren P Tate, Stephanie M Hughes, Wickliffe C Abraham
Alzheimer's disease (AD) is a neurodegenerative disease driven in large part by accumulated deposits in the brain of the amyloid precursor protein (APP) cleavage product amyloid-β peptide (Aβ). However, AD is also characterised by reductions in secreted amyloid precursor protein-alpha (sAPPα), an alternative cleavage product of APP. In contrast to the neurotoxicity of accumulated Αβ, sAPPα has many neuroprotective and neurotrophic properties. Increasing sAPPα levels has the potential to serve as a therapeutic treatment that mitigates the effects of Aβ and rescue cognitive function...
February 9, 2018: Molecular Brain
https://www.readbyqxmd.com/read/29426351/poly-arginine-r18-and-r18d-d-enantiomer-peptides-reduce-infarct-volume-and-improves-behavioural-outcomes-following-perinatal-hypoxic-ischaemic-encephalopathy-in-the-p7-rat
#4
Adam B Edwards, Jane L Cross, Ryan S Anderton, Neville W Knuckey, Bruno P Meloni
We examined the neuroprotective efficacy of the poly-arginine peptide R18 and its D-enantiomer R18D in a perinatal hypoxic-ischaemic (HI) model in P7 Sprague-Dawley rats. R18 and R18D peptides were administered intraperitoneally at doses of 30, 100, 300 or 1000 nmol/kg immediately after HI (8% O2/92%N2 for 2.5 h). The previously characterised neuroprotective JNKI-1-TATD peptide at a dose of 1000 nmol/kg was used as a control. Infarct volume and behavioural outcomes were measured 48 h after HI. For the R18 and R18D doses examined, total infarct volume was reduced by 25...
February 9, 2018: Molecular Brain
https://www.readbyqxmd.com/read/29394901/foxg1-deletion-impairs-the-development-of-the-epithalamus
#5
Bin Liu, Kaixing Zhou, Xiaojing Wu, Chunjie Zhao
The epithalamus, which is dorsal to the thalamus, consists of the habenula, pineal gland and third ventricle choroid plexus and plays important roles in the stress response and sleep-wake cycle in vertebrates. During development, the epithalamus arises from the most dorsal part of prosomere 2. However, the mechanism underlying epithalamic development remains largely unknown. Foxg1 is critical for the development of the telencephalon, but its role in diencephalic development has been under-investigated. Patients suffering from FOXG1-related disorders exhibit severe anxiety, sleep disturbance and choroid plexus cysts, indicating that Foxg1 likely plays a role in epithalamic development...
February 2, 2018: Molecular Brain
https://www.readbyqxmd.com/read/29370841/expression-of-functional-inhibitory-neurotransmitter-transporters-glyt1-gat-1-and-gat-3-by-astrocytes-of-inferior-colliculus-and-hippocampus
#6
Elsa Ghirardini, Simon L Wadle, Vanessa Augustin, Jasmin Becker, Sina Brill, Julia Hammerich, Gerald Seifert, Jonathan Stephan
Neuronal inhibition is mediated by glycine and/or GABA. Inferior colliculus (IC) neurons receive glycinergic and GABAergic inputs, whereas inhibition in hippocampus (HC) predominantly relies on GABA. Astrocytes heterogeneously express neurotransmitter transporters and are expected to adapt to the local requirements regarding neurotransmitter homeostasis. Here we analyzed the expression of inhibitory neurotransmitter transporters in IC and HC astrocytes using whole-cell patch-clamp and single-cell reverse transcription-PCR...
January 25, 2018: Molecular Brain
https://www.readbyqxmd.com/read/29335006/genetic-dissection-of-the-neuro-glio-vascular-machinery-in-the-adult-brain
#7
Gregory W Kirschen, Rachel Kéry, Hanxiao Liu, Afrinash Ahamad, Liang Chen, Wendy Akmentin, Ramya Kumar, Joel Levine, Qiaojie Xiong, Shaoyu Ge
The adult brain actively controls its metabolic homeostasis via the circulatory system at the blood brain barrier interface. The mechanisms underlying the functional coupling from neuron to vessel remain poorly understood. Here, we established a novel method to genetically isolate the individual components of this coupling machinery using a combination of viral vectors. We first discovered a surprising non-uniformity of the glio-vascular structure in different brain regions. We carried out a viral injection screen and found that intravenous Canine Adenovirus 2 (CAV2) preferentially targeted perivascular astrocytes throughout the adult brain, with sparing of the hippocampal hilus from infection...
January 15, 2018: Molecular Brain
https://www.readbyqxmd.com/read/29334986/bridging-pro-inflammatory-signals-synaptic-transmission-and-protection-in-spinal-explants-in-vitro
#8
M Medelin, V Giacco, A Aldinucci, G Castronovo, E Bonechi, A Sibilla, M Tanturli, M Torcia, L Ballerini, F Cozzolino, C Ballerini
Multiple sclerosis is characterized by tissue atrophy involving the brain and the spinal cord, where reactive inflammation contributes to the neurodegenerative processes. Recently, the presence of synapse alterations induced by the inflammatory responses was suggested by experimental and clinical observations, in experimental autoimmune encephalomyelitis mouse model and in patients, respectively. Further knowledge on the interplay between pro-inflammatory agents, neuroglia and synaptic dysfunction is crucial to the design of unconventional protective molecules...
January 15, 2018: Molecular Brain
https://www.readbyqxmd.com/read/29301575/warburg-effect-hypothesis-in-autism-spectrum-disorders
#9
REVIEW
Alexandre Vallée, Jean-Noël Vallée
Autism spectrum disorder (ASD) is a neurodevelopmental disease which is characterized by a deficit in social interactions and communication with repetitive and restrictive behavior. In altered cells, metabolic enzymes are modified by the dysregulation of the canonical WNT/β-catenin pathway. In ASD, the canonical WNT/β-catenin pathway is upregulated. We focus this review on the hypothesis of Warburg effect stimulated by the overexpression of the canonical WNT/β-catenin pathway in ASD. Upregulation of WNT/β-catenin pathway induces aerobic glycolysis, named Warburg effect, through activation of glucose transporter (Glut), pyruvate kinase M2 (PKM2), pyruvate dehydrogenase kinase 1(PDK1), monocarboxylate lactate transporter 1 (MCT-1), lactate dehydrogenase kinase-A (LDH-A) and inactivation of pyruvate dehydrogenase complex (PDH)...
January 4, 2018: Molecular Brain
https://www.readbyqxmd.com/read/29284498/accelerated-super-resolution-imaging-with-fret-paint
#10
Jongjin Lee, Sangjun Park, Wooyoung Kang, Sungchul Hohng
Super-resolution fluorescence microscopy in the current form is hard to be used to image the neural connectivity of thick tissue samples due to problems such as slow imaging speed, severe photobleaching of fluorescent probes, and high background noise. Recently developed DNA-PAINT solved the photobleaching problem, but its imaging speed is extremely low. We report accelerated super-resolution fluorescence microscopy named FRET-PAINT. Compared to conventional DNA-PAINT, the imaging speed of the microscopy increases up to ~30-fold...
December 28, 2017: Molecular Brain
https://www.readbyqxmd.com/read/29282074/the-rap-activator-gef26-regulates-synaptic-growth-and-neuronal-survival-via-inhibition-of-bmp-signaling
#11
Keunjung Heo, Minyeop Nahm, Min-Jung Lee, Young-Eun Kim, Chang-Seok Ki, Seung Hyun Kim, Seungbok Lee
In Drosophila, precise regulation of BMP signaling is essential for normal synaptic growth at the larval neuromuscular junction (NMJ) and neuronal survival in the adult brain. However, the molecular mechanisms underlying fine-tuning of BMP signaling in neurons remain poorly understood. We show that loss of the Drosophila PDZ guanine nucleotide exchange factor Gef26 significantly increases synaptic growth at the NMJ and enhances BMP signaling in motor neurons. We further show that Gef26 functions upstream of Rap1 in motor neurons to restrain synaptic growth...
December 28, 2017: Molecular Brain
https://www.readbyqxmd.com/read/29258546/hippocampal-calpain-is-required-for-the-consolidation-and-reconsolidation-but-not-extinction-of-contextual-fear-memory
#12
Taikai Nagayoshi, Kiichiro Isoda, Nori Mamiya, Satoshi Kida
Memory consolidation, reconsolidation, and extinction have been shown to share similar molecular signatures, including new gene expression. Calpain is a Ca2+-dependent protease that exerts its effects through the proteolytic cleavage of target proteins. Neuron-specific conditional deletions of calpain 1 and 2 impair long-term potentiation in the hippocampus and spatial learning. Moreover, recent studies have suggested distinct roles of calpain 1 and 2 in synaptic plasticity. However, the role of hippocampal calpain in memory processes, especially memory consolidation, reconsolidation, and extinction, is still unclear...
December 19, 2017: Molecular Brain
https://www.readbyqxmd.com/read/29249203/characterization-of-excitatory-synaptic-transmission-in-the-anterior-cingulate-cortex-of-adult-tree-shrew
#13
Xu-Hui Li, Qian Song, Qi-Yu Chen, Jing-Shan Lu, Tao Chen, Min Zhuo
The tree shrew, as a primate-like animal model, has been used for studying high brain functions such as social emotion and spatial learning memory. However, little is known about the excitatory synaptic transmission in cortical brain areas of the tree shrew. In the present study, we have characterized the excitatory synaptic transmission and intrinsic properties of pyramidal neurons in the anterior cingulate cortex (ACC) of the adult tree shrew, a key cortical region for pain perception and emotion. We found that glutamate is the major excitatory transmitter for fast synaptic transmission...
December 18, 2017: Molecular Brain
https://www.readbyqxmd.com/read/29233183/restoring-synaptic-plasticity-and-memory-in-mouse-models-of-alzheimer-s-disease-by-pkr-inhibition
#14
Kyoung-Doo Hwang, Myeong Seong Bak, Sang Jeong Kim, Sangmyung Rhee, Yong-Seok Lee
Alzheimer's disease (AD) is a neurodegenerative disorder associated with deficits in cognition and synaptic plasticity. While accumulation of amyloid β (Aβ) and hyper-phosphorylation of tau are parts of the etiology, AD can be caused by a large number of different genetic mutations and other unknown factors. Considering such a heterogeneous nature of AD, it would be desirable to develop treatment strategies that can improve memory irrespective of the individual causes. Reducing the phosphorylation of eukaryotic translation initiation factor 2α (eIF2α) was shown to enhance long-term memory and synaptic plasticity in naïve mice...
December 13, 2017: Molecular Brain
https://www.readbyqxmd.com/read/29233179/immature-morphological-properties-in-subcellular-scale-structures-in-the-dentate-gyrus-of-schnurri-2-knockout-mice-a-model-for-schizophrenia-and-intellectual-disability
#15
Akito Nakao, Naoyuki Miyazaki, Koji Ohira, Hideo Hagihara, Tsuyoshi Takagi, Nobuteru Usuda, Shunsuke Ishii, Kazuyoshi Murata, Tsuyoshi Miyakawa
Accumulating evidence suggests that subcellular-scale structures such as dendritic spine and mitochondria may be involved in the pathogenesis/pathophysiology of schizophrenia and intellectual disability. Previously, we proposed mice lacking Schnurri-2 (Shn2; also called major histocompatibility complex [MHC]-binding protein 2 [MBP-2], or human immunodeficiency virus type I enhancer binding protein 2 [HIVEP2]) as a schizophrenia and intellectual disability model with mild chronic inflammation. In the mutants' brains, there are increases in C4b and C1q genes, which are considered to mediate synapse elimination during postnatal development...
December 12, 2017: Molecular Brain
https://www.readbyqxmd.com/read/29221469/correction-to-the-role-of-melatonin-in-the-onset-and-progression-of-type-3-diabetes
#16
Juhyun Song, Daniel J Whitcomb, Byeong C Kim
MOLECULAR BRAIN (2017) 10:35 DOI: 10.1186/S13041-017-0315-X: In the original version of this article [1], published on 1 August 2017, Fig. 3 contains a typo. In this Correction the incorrect and correct version of Fig. 3 are shown. - Fig. 3 was originally published like this: - The correct version of Fig. 3 looks like this.
December 8, 2017: Molecular Brain
https://www.readbyqxmd.com/read/29202853/increased-pkm%C3%AE-activity-impedes-lateral-movement-of-glua2-containing-ampa-receptors
#17
Nam-Kyung Yu, Heesoo Uhm, Jaehoon Shim, Jun-Hyeok Choi, Sangsu Bae, Todd Charlton Sacktor, Sungchul Hohng, Bong-Kiun Kaang
Protein kinase M zeta (PKMζ), a constitutively active, atypical protein kinase C isoform, maintains a high level of expression in the brain after the induction of learning and long-term potentiation (LTP). Further, its overexpression enhances long-term memory and LTP. Thus, multiple lines of evidence suggest a significant role for persistently elevated PKMζ levels in long-term memory. The molecular mechanisms of how synaptic properties are regulated by the increase in PKMζ, however, are still largely unknown...
November 29, 2017: Molecular Brain
https://www.readbyqxmd.com/read/29187220/genomic-copy-number-variation-analysis-in-multiple-system-atrophy
#18
Yuka Hama, Masataka Katsu, Ichigaku Takigawa, Ichiro Yabe, Masaaki Matsushima, Ikuko Takahashi, Takayuki Katayama, Jun Utsumi, Hidenao Sasaki
Genomic variation includes single-nucleotide variants, small insertions or deletions (indels), and copy number variants (CNVs). CNVs affect gene expression by altering the genome structure and transposable elements within a region. CNVs are greater than 1 kb in size; hence, CNVs can produce more variation than can individual single-nucleotide variations that are detected by next-generation sequencing. Multiple system atrophy (MSA) is an α-synucleinopathy adult-onset disorder. Pathologically, it is characterized by insoluble aggregation of filamentous α-synuclein in brain oligodendrocytes...
November 29, 2017: Molecular Brain
https://www.readbyqxmd.com/read/29187215/criteria-for-identifying-the-molecular-basis-of-the-engram-camkii-pkmzeta
#19
REVIEW
John Lisman
The engram refers to the molecular changes by which a memory is stored in the brain. Substantial evidence suggests that memory involves learning-dependent changes at synapses, a process termed long-term potentiation (LTP). Thus, understanding the storages process that underlies LTP may provide insight into how the engram is stored. LTP involves induction, maintenance (storage), and expression sub-processes; special tests are required to specifically reveal properties of the storage process. The strongest of these is the Erasure test in which a transiently applied agent that attacks a putative storage molecule may lead to persistent erasure of previously induced LTP/memory...
November 29, 2017: Molecular Brain
https://www.readbyqxmd.com/read/29183391/oxidative-stress-and-cellular-pathologies-in-parkinson-s-disease
#20
REVIEW
Lesly Puspita, Sun Young Chung, Jae-Won Shim
Parkinson's disease (PD) is a chronic and progressive neurodegeneration of dopamine neurons in the substantia nigra. The reason for the death of these neurons is unclear; however, studies have demonstrated the potential involvement of mitochondria, endoplasmic reticulum, α-synuclein or dopamine levels in contributing to cellular oxidative stress as well as PD symptoms. Even though those papers had separately described the individual roles of each element leading to neurodegeneration, recent publications suggest that neurodegeneration is the product of various cellular interactions...
November 28, 2017: Molecular Brain
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