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Hirotaka Sekiguchi, Masatsugu Moriwaki, Shuji Iritani, Chikako Habuchi, Youta Torii, Kentaro Umeda, Hiroshige Fujishiro, Mari Yoshida, Kiyoshi Fujita
We herein report the case of a 75-year-old male who had shown many psychiatric symptoms, but whose autopsy disclosed the presence of dementia with Lewy bodies (DLB). When he was 70 years old, the patient had presented with stereotyped behavior, dietary changes, and a decline in social interpersonal conduct in clinical settings, and it was thought that these symptoms were consistent with a behavioral variant of frontotemporal dementia (bvFTD), and he lacked the core features of DLB. Nevertheless, this case was pathologically defined as the limbic type of DLB after he died at the age of 75 years...
October 14, 2016: Clinical Neuropathology
Marthe H R Ludtmann, Plamena R Angelova, Natalia N Ninkina, Sonia Gandhi, Vladimir L Buchman, Andrey Y Abramov
: Misfolded α-synuclein is a key factor in the pathogenesis of Parkinson's disease (PD). However, knowledge about a physiological role for the native, unfolded α-synuclein is limited. Using brains of mice lacking α-, β-, and γ-synuclein, we report that extracellular monomeric α-synuclein enters neurons and localizes to mitochondria, interacts with ATP synthase subunit α, and modulates ATP synthase function. Using a combination of biochemical, live-cell imaging and mitochondrial respiration analysis, we found that brain mitochondria of α-, β-, and γ-synuclein knock-out mice are uncoupled, as characterized by increased mitochondrial respiration and reduced mitochondrial membrane potential...
October 12, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Abinaya Chandrasekaran, Hasan X Avci, Marcel Leist, Julianna Kobolák, Andras Dinnyés
Astrocytes have a central role in brain development and function, and so have gained increasing attention over the past two decades. Consequently, our knowledge about their origin, differentiation and function has increased significantly, with new research showing that astrocytes cultured alone or co-cultured with neurons have the potential to improve our understanding of various central nervous system diseases, such as amyotrophic lateral sclerosis, Alzheimer's disease, or Alexander disease. The generation of astrocytes derived from pluripotent stem cells (PSCs) opens up a new area for studying neurologic diseases in vitro; these models could be exploited to identify and validate potential drugs by detecting adverse effects in the early stages of drug development...
2016: Frontiers in Cellular Neuroscience
Jessica M Kelly, Allison Bradbury, Douglas R Martin, Mark E Byrne
Approximately 1 in 5000-8000 children are born annually with a lysosomal storage disease (LSD), which affects their cells' ability to break down naturally occurring substrates. Accumulation, or "storage," of undegraded substrates leads to a wide variety of clinical symptoms, and early mortality. Currently, for LSDs with central nervous system (CNS) involvement, there is no available treatment. Four methods of treatment are being explored in clinical trials and preclinical settings: enzyme replacement therapy, ex vivo gene therapy, in vivo gene therapy, and nanoparticle-based therapy...
October 7, 2016: Progress in Neurobiology
Balachandar Radhakrishnan, A Alwin Prem Anand
MicroRNAs (miRNAs) are a class of small regulatory RNAs involved in gene regulation. The regulation is effected by either translational inhibition or transcriptional silencing. In vertebrates, the importance of miRNA in development was discovered from mice and zebrafish dicer knockouts. The miRNA-9 (miR-9) is one of the most highly expressed miRNAs in the early and adult vertebrate brain. It has diverse functions within the developing vertebrate brain. In this article, the role of miR-9 in the developing forebrain (telencephalon and diencephalon), midbrain, hindbrain, and spinal cord of vertebrate species is highlighted...
2016: Journal of Experimental Neuroscience
Soujanya D Yelamanchi, Manish Kumar, Anil K Madugundu, Lathika Gopalakrishnan, Gourav Dey, Sandip Chavan, Gajanan Sathe, Premendu P Mathur, Harsha Gowda, Anita Mahadevan, Susarla K Shankar, T S Keshava Prasad
The pineal gland is a neuroendocrine gland located at the center of the brain. It is known to regulate various physiological functions in the body through secretion of the neurohormone melatonin. Comprehensive characterization of the human pineal gland proteome has not been undertaken to date. We employed a high-resolution mass spectrometry-based approach to characterize the proteome of the human pineal gland. A total of 5874 proteins were identified from the human pineal gland in this study. Of these, 5820 proteins were identified from the human pineal gland for the first time...
October 7, 2016: Molecular BioSystems
Anna Dora Manca, Mirko Grimaldi
Speech sound perception is one of the most fascinating tasks performed by the human brain. It involves a mapping from continuous acoustic waveforms onto the discrete phonological units computed to store words in the mental lexicon. In this article, we review the magnetoencephalographic studies that have explored the timing and morphology of the N1m component to investigate how vowels and consonants are computed and represented within the auditory cortex. The neurons that are involved in the N1m act to construct a sensory memory of the stimulus due to spatially and temporally distributed activation patterns within the auditory cortex...
2016: Frontiers in Psychology
Xiu-Li Cao, Xing Zhang, Yu-Fei Zhang, Yi-Zhe Zhang, Chang-Geng Song, Fan Liu, Yi-Yang Hu, Min-Hua Zheng, Hua Han
Ttyh1 is a murine homolog of the Drosophila Tweety and is predicted as a five-pass transmembrane protein. The Ttyh1 mRNA is expressed in mouse brain tissues with a restricted pattern and in human glioma cells. Ttyh1 protein may function as a large-conductance chloride channel, however, the role of Ttyh1 in normal neural development and tumorigenesis has been largely unknown, at least partially due to the lack of effective antibodies. Here we report the expression in E. coli and purification of two recombinant Ttyh1 protein fragments corresponding to one of the predicted extracellular domains and the carboxyl terminus of the mouse Ttyh1...
September 24, 2016: Protein Expression and Purification
Nabi Zorlu, Vanessa Louise Cropley, Pelin Kurtgoz Zorlu, Dursun Hakan Delibas, Zehra Hilal Adibelli, Emel Pasa Baskin, Özgür Sipahi Esen, Emre Bora, Christos Pantelis
Findings of surface-based morphometry studies in major depressive disorder (MDD) are still inconsistent. Given that cigarette smoking is highly prevalent in MDD and has documented negative effects on the brain, it is possible that some of the inconsistencies may be partly explained by cigarette use. The aim of the current study was to examine the influence of cigarette smoking on brain structure in MDD. 50 MDD patients (25 smokers and 25 non-smokers) and 22 age, education, gender and BMI matched non-smoker healthy controls underwent structural magnetic resonance imaging...
September 13, 2016: Journal of Psychiatric Research
Sabrina Trapp, Sonja A Kotz
Both theoretical proposals and empirical studies suggest that the brain interprets sensory input based on expectations to mitigate computational burden. However, as social beings, much of sensory input is affectively loaded - e.g., the smile of a partner, the critical voice of a boss, or the welcoming gesture of a friend. Given that affective information is highly complex and often ambiguous, building up expectations of upcoming affective sensory input may greatly contribute to its rapid and efficient processing...
2016: Frontiers in Psychology
Ting-Hao Huang, Tarciso Velho, Carlos Lois
We used a synthetic genetic system based on ligand-induced intramembrane proteolysis to monitor cell-cell contacts in animals. Upon ligand-receptor interaction in sites of cell-cell contact, the transmembrane domain of an engineered receptor is cleaved by intramembrane proteolysis and releases a protein fragment that regulates transcription in the interacting partners. We demonstrate that the system can be used to regulate gene expression between interacting cells both in vitro and in vivo, in transgenic Drosophila We show that the system allows for detection of interactions between neurons and glia in the Drosophila nervous system...
September 22, 2016: Development
Yuda Turana
Observational studies have conveyed the connection between hypertension and cognitive impairment. Several forms of dementia are more frequent in hypertensive subjects or those with previous history of hypertension compared to subjects with normal blood pressure.In many studies, hypertension occuring in mid-life is a risk factor of dementia occuring in later age. Long-standing hypertension will induce structural damages in the brain. It is also widely known that hypertension attributes to small vessel diseases causing lacunar infarcts and white matter lesions associated with cognitive decline...
September 2016: Journal of Hypertension
Fabian Güiza, Bart Depreitere, Ian Piper, Giuseppe Citerio, Philippe G Jorens, Andrew Maas, Martin U Schuhmann, Tsz-Yan Milly Lo, Rob Donald, Patricia Jones, Gottlieb Maier, Greet Van den Berghe, Geert Meyfroidt
OBJECTIVE: A model for early detection of episodes of increased intracranial pressure in traumatic brain injury patients has been previously developed and validated based on retrospective adult patient data from the multicenter Brain-IT database. The purpose of the present study is to validate this early detection model in different cohorts of recently treated adult and pediatric traumatic brain injury patients. DESIGN: Prognostic modeling. Noninterventional, observational, retrospective study...
September 14, 2016: Critical Care Medicine
Arik A Zur, Huan-Chieh Chien, Evan Augustyn, Andrew Flint, Nathan Heeren, Karissa Finke, Christopher Hernandez, Logan Hansen, Sydney Miller, Lawrence Lin, Kathleen M Giacomini, Claire Colas, Avner Schlessinger, Allen A Thomas
Large neutral amino acid transporter 1 (LAT1) is a solute carrier protein located primarily in the blood-brain barrier (BBB) that offers the potential to deliver drugs to the brain. It is also up-regulated in cancer cells, as part of a tumor's increased metabolic demands. Previously, amino acid prodrugs have been shown to be transported by LAT1. Carboxylic acid bioisosteres may afford prodrugs with an altered physicochemical and pharmacokinetic profile than those derived from natural amino acids, allowing for higher brain or tumor levels of drug and/or lower toxicity...
October 15, 2016: Bioorganic & Medicinal Chemistry Letters
Eduardo A Nillni
The last decade had witnessed a tremendous progress in our understanding of the causes of metabolic diseases including obesity. Among the contributing factors regulating energy balance are nutrient sensors such as sirtuins. Sirtuin1 (Sirt1), a NAD + - dependent deacetylase is affected by diet, environmental stress, and also plays a critical role in metabolic health by deacetylating proteins in many tissues, including liver, muscle, adipose tissue, heart, endothelium, and in the complexity of the hypothalamus...
September 7, 2016: Molecular and Cellular Endocrinology
Anja Mikolić, Neala Schönwald, Martina Piasek
The effects of cadmium (Cd) were evaluated in offspring exposed from birth until weaning (neonatal day 0-21) and 4 weeks after exposure cessation focusing on iron (Fe) and zinc (Zn) levels in organs and hematological parameters. Wistar female rats were administered 50mg Cd/L in drinking water (Cd-exposed) for 4 weeks before mating and during 3 weeks of gestation plus 3 weeks of lactation. Controls were supplied drinking water. At birth, part of Cd-exposed dams' litters was cross-fostered to control dams (CCd group) and their control litters were cross-fostered to Cd-exposed dams (CdC group)...
December 2016: Journal of Trace Elements in Medicine and Biology
Mirjam Sibbe, Akos Kulik
Adult hippocampal neurogenesis has been implicated in several brain functions, including learning and memory processes. It also plays an important role in the aetiology of anxiety disorders, depression and age-related deficits. The endogenous stem cell pool is also known to hold great potential for ameliorating the diseased or aged brain. It has been shown that certain brain activities lead to an adjustment of adult neurogenesis, which can further be controlled by the interplay between inhibitory and excitatory processes...
September 6, 2016: Molecular Neurobiology
Eunju Leem, Kyoung Hoon Jeong, So-Yoon Won, Won-Ho Shin, Sang Ryong Kim
Although accumulating evidence suggests that microglia-mediated neuroinflammation may be crucial for the initiation and progression of Parkinson's disease (PD), and that the control of neuroinflammation may be a useful strategy for preventing the degeneration of nigrostriatal dopaminergic (DA) projections in the adult brain, it is still unclear what kinds of endogenous biomolecules initiate microglial activation, consequently resulting in neurodegeneration. Recently, we reported that the increase in the levels of prothrombin kringle-2 (pKr-2), which is a domain of prothrombin that is generated by active thrombin, can lead to disruption of the nigrostriatal DA projection...
August 2016: Experimental Neurobiology
Masae Naruse, Yasuki Ishizaki, Kazuhiro Ikenaka, Aoi Tanaka, Seiji Hitoshi
Oligodendrocyte precursor cells (OPCs) appear in the late embryonic brain, mature into oligodendrocytes (OLs), and form myelin in the postnatal brain. It has been proposed that early born OPCs derived from the ventral forebrain are eliminated postnatally and late-born OLs predominate in the adult mouse cortex. However, the temporal and regional niche for cortical OL generation, which persists throughout life in adult mammals, remains to be determined. Our recent study provides new insight into self-renewing and multipotent neural stem cells (NSCs)...
August 29, 2016: Journal of Physiological Sciences: JPS
Esmat Fathi, Fatemeh Hedayati Katouli, Gholam Hossein Riazi, Marzieh Dehghan Shasaltaneh, Elham Parandavar, Samaneh Bayati, Ali Afrasiabi, Reza Nazari
Reelin is an extracellular glycoprotein which contributes to synaptic plasticity and function of memory in the adult brain. It has been indicated that the Reelin signaling cascade participates in Alzheimer's disease (AD). Besides the neurons, glial cells such as astrocytes also express Reelin protein. While functional loss of astrocytes has been reported to be associated with AD, dysfunction of astrocytic Reelin signaling pathway has not received much attention. Therefore, we investigated the effects of α-boswellic acid (ABA) as one of the major component of Boswellia serrata resin on primary fetal human astrocytes under a stress paradigm as a possible model for AD through study on Reelin cascade...
August 27, 2016: Neuromolecular Medicine
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