Mice, Inbred C57BL

Publication Title: 
Nature Neuroscience

Brain-derived neurotrophic factor (BDNF) has a crucial role in modulating neural and behavioral plasticity to drugs of abuse. We found a persistent downregulation of exon-specific Bdnf expression in the ventral tegmental area (VTA) in response to chronic opiate exposure, which was mediated by specific epigenetic modifications at the corresponding Bdnf gene promoters.

Author(s): 
Koo, Ja Wook
Mazei-Robison, Michelle S.
LaPlant, Quincey
Egervari, Gabor
Braunscheidel, Kevin M.
Adank, Danielle N.
Ferguson, Deveroux
Feng, Jian
Sun, HaoSheng
Scobie, Kimberly N.
Damez-Werno, Diane M.
Ribeiro, Efrain
PeÒa, Catherine Jensen
Walker, Deena
Bagot, Rosemary C.
Cahill, Michael E.
Anderson, Sarah Ann R.
LabontÈ, Benoit
Hodes, Georgia E.
Browne, Heidi
Chadwick, Benjamin
Robison, Alfred J.
Vialou, Vincent F.
Dias, Caroline
Lorsch, Zachary
Mouzon, Ezekiell
Lobo, Mary Kay
Dietz, David M.
Russo, Scott J.
Neve, Rachael L.
Hurd, Yasmin L.
Nestler, Eric J.
Publication Title: 
Neuron

One of the exceptional properties of the brain is its ability to acquire new knowledge through learning and to store that information through memory. The epigenetic mechanisms linking changes in neuronal transcriptional programs to behavioral plasticity remain largely unknown. Here, we identify the epigenetic signature of the neuronal enhancers required for transcriptional regulation of synaptic plasticity genes during memory formation, linking this to Reelin signaling.

Author(s): 
Telese, Francesca
Ma, Qi
Perez, Patricia Montilla
Notani, Dimple
Oh, Soohwan
Li, Wenbo
Comoletti, Davide
Ohgi, Kenneth A.
Taylor, Havilah
Rosenfeld, Michael G.
Publication Title: 
Nature Medicine

Improved treatment for major depressive disorder (MDD) remains elusive because of the limited understanding of its underlying biological mechanisms. It is likely that stress-induced maladaptive transcriptional regulation in limbic neural circuits contributes to the development of MDD, possibly through epigenetic factors that regulate chromatin structure.

Author(s): 
Sun, HaoSheng
Damez-Werno, Diane M.
Scobie, Kimberly N.
Shao, Ning-Yi
Dias, Caroline
Rabkin, Jacqui
Koo, Ja Wook
Korb, Erica
Bagot, Rosemary C.
Ahn, Francisca H.
Cahill, Michael E.
LabontÈ, Benoit
Mouzon, Ezekiell
Heller, Elizabeth A.
Cates, Hannah
Golden, Sam A.
Gleason, Kelly
Russo, Scott J.
Andrews, Simon
Neve, Rachael
Kennedy, Pamela J.
Maze, Ian
Dietz, David M.
Allis, C. David
Turecki, Gustavo
Varga-Weisz, Patrick
Tamminga, Carol
Shen, Li
Nestler, Eric J.
Publication Title: 
The Journal of Neuroscience: The Official Journal of the Society for Neuroscience

Epigenetic processes that regulate histone acetylation play an essential role in behavioral and molecular responses to cocaine. To date, however, only a small fraction of the mechanisms involved in the addiction-associated acetylome have been investigated. Members of the bromodomain and extraterminal (BET) family of epigenetic "reader" proteins (BRD2, BRD3, BRD4, and BRDT) bind acetylated histones and serve as a scaffold for the recruitment of macromolecular complexes to modify chromatin accessibility and transcriptional activity.

Author(s): 
Sartor, Gregory C.
Powell, Samuel K.
Brothers, Shaun P.
Wahlestedt, Claes
Publication Title: 
Epigenetics

Epigenetic mechanisms can mediate gene-environment interactions relevant for complex disorders. The BDNF gene is crucial for development and brain plasticity, is sensitive to environmental stressors, such as hypoxia, and harbors the functional SNP rs6265 (Val(66)Met), which creates or abolishes a CpG dinucleotide for DNA methylation.

Author(s): 
Ursini, Gianluca
Cavalleri, Tommaso
Fazio, Leonardo
Angrisano, Tiziana
Iacovelli, Luisa
Porcelli, Annamaria
Maddalena, Giancarlo
Punzi, Giovanna
Mancini, Marina
Gelao, Barbara
Romano, Raffaella
Masellis, Rita
Calabrese, Francesca
Rampino, Antonio
Taurisano, Paolo
Di Giorgio, Annabella
Keller, Simona
Tarantini, Letizia
Sinibaldi, Lorenzo
Quarto, Tiziana
Popolizio, Teresa
Caforio, Grazia
Blasi, Giuseppe
Riva, Marco A.
De Blasi, Antonio
Chiariotti, Lorenzo
Bollati, Valentina
Bertolino, Alessandro
Publication Title: 
Proceedings of the National Academy of Sciences of the United States of America

Recent studies have identified impairments in neural induction and in striatal and cortical neurogenesis in Huntington's disease (HD) knock-in mouse models and associated embryonic stem cell lines. However, the potential role of these developmental alterations for HD pathogenesis and progression is currently unknown. To address this issue, we used BACHD:CAG-Cre(ERT2) mice, which carry mutant huntingtin (mHtt) modified to harbor a floxed exon 1 containing the pathogenic polyglutamine expansion (Q97).

Author(s): 
Molero, Aldrin E.
Arteaga-Bracho, Eduardo E.
Chen, Christopher H.
Gulinello, Maria
Winchester, Michael L.
Pichamoorthy, Nandini
Gokhan, Solen
Khodakhah, Kamran
Mehler, Mark F.
Publication Title: 
Psychopharmacology

The effects of naltrexone on the increase in locomotor activity induced by a low dose (1.35 g/kg IP) of ethanol and on the duration of loss of righting reflex after a high dose (3.5 g/kg) of ethanol were studied in BALB/c, DBA/2, and C57BL/6 mice. Ethanol increased locomotor activity in DBA and BALB mice, but not in C57BL mice. Naltrexone, at a dose of 0.1 mg/kg, antagonized the ethanol-induced increase in locomotion similarly in DBA and BALB mice. The duration of loss of righting reflex was, however, differentially affected in all three strains by naltrexone.

Author(s): 
Kiianmaa, K.
Hoffman, P. L.
Tabakoff, B.
Publication Title: 
Psychopharmacology

The actions of indomethacin on the effects produced by ethanol were determined in rats and mice by measuring motor coordination (Rotorod test), sleep times, and body temperatures. Mice receiving indomethacin in combination with ethanol slept shorter times than those receiving ethanol alone. The blood and brain ethanol concentrations at time of awakening were significantly higher in the mice receiving the combination of drugs. Ethanol actions on motor impairment in rats and mice and on hypothermia in mice were not altered by pharmacologically relevant doses of indomethacin.

Author(s): 
Greizerstein, H. B.
Publication Title: 
Life Sciences

The influence of four centrally-acting alpha-1 adrenoceptor agonists, namely, 2(2-chloro-5-trifluoromethylphenylimino) imidazolidine (St 587), cirazoline, (-) 1,2,3,4-tetrahydro-8-methoxy-5-methylthio-2-naphthalenamine ((-)SKF 89748A) and 2-(2-methylindazol-4-imino)imidazolidine (Sgd 101/75) on the pharmacological effects of ethanol was investigated. All four drugs reduced the duration of ethanol-induced hypnosis in C57B1/6 mice, this effect being proportional to their relative potencies to exert central alpha-1 agonism.

Author(s): 
Menon, M. K.
Dinovo, E. C.
Haddox, V. G.
Publication Title: 
Brain Research Bulletin

Recent reports of in vivo antagonism of the acute anti-conflict, ataxic, and lethal effects of ethanol with the partial inverse agonist imidazobenzodiazepine Ro15-4513 implicate the GABAa/benzodiazepine receptor in mediating several acute effects of ethanol. These data raise the question as to whether all of the acute effects of ethanol can be antagonized by Ro15-4513. The present study addressed this issue by investigating the effect of Ro15-4513 on ethanol-induced loss of righting reflex and hypothermia in mice.

Author(s): 
Syapin, P. J.
Gee, K. W.
Alkana, R. L.

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