Cerebral Cortex

Publication Title: 
Journal of Affective Disorders

BACKGROUND: Generalized anxiety disorder (GAD) is a prevalent anxiety disorder, but its neurobiological basis has been poorly studied. A few cognitive models have been proposed for understanding GAD development and maintenance. The aim of this study is to review functional Magnetic Resonance Image (fMRI) studies conducted with GAD patients and evaluate if they support and underpin the theoretical cognitive models proposed for this anxiety disorder. METHODS: A literature systematic review was undertaken in PubMed and ISI databases with no time limits.

Mochcovitch, Marina Dyskant
da Rocha Freire, Rafael Christophe
Garcia, Rafael Ferreira
Nardi, Antonio E.
Publication Title: 
Nature Communications

It is hypothesized that a common underlying mechanism links multiple neurodegenerative disorders. Here we show that transitional endoplasmic reticulum ATPase (TERA)/valosin-containing protein (VCP)/p97 directly binds to multiple polyglutamine disease proteins (huntingtin, ataxin-1, ataxin-7 and androgen receptor) via polyglutamine sequence. Although normal and mutant polyglutamine proteins interact with TERA/VCP/p97, only mutant proteins affect dynamism of TERA/VCP/p97.

Fujita, Kyota
Nakamura, Yoko
Oka, Tsutomu
Ito, Hikaru
Tamura, Takuya
Tagawa, Kazuhiko
Sasabe, Toshikazu
Katsuta, Asuka
Motoki, Kazumi
Shiwaku, Hiroki
Sone, Masaki
Yoshida, Chisato
Katsuno, Masahisa
Eishi, Yoshinobu
Murata, Miho
Taylor, J. Paul
Wanker, Erich E.
Kono, Kazuteru
Tashiro, Satoshi
Sobue, Gen
La Spada, Albert R.
Okazawa, Hitoshi
Publication Title: 
Journal of Neurology, Neurosurgery, and Psychiatry

Three cases with intracranial lesions developed evidence of disseminated intravascular coagulation which was confirmed at necropsy. The factors engendering this state, including release of potent thromboplastin from neural tissue are discussed and the danger of this intermediary mechanism of disease increasing the mortality of intracranial disease is demonstrated. Careful haematological investigation of all patients with intracranial disease is therefore advised, especially if they manifest evidence of a bleeding tendency.

Preston, F. E.
Malia, R. G.
Sworn, M. J.
Timperley, W. R.
Blackburn, E. K.
Publication Title: 
Schizophrenia Research

Annett, Yeo et al. and Klar have each proposed theories that relate the genetics of cerebral lateralization to predisposition to psychosis. These theories are considered in relation to the central paradox that psychosis is associated with a substantial biological disadvantage. Annett's heterozygote advantage hypothesis critically identified lateralization as a major determinant of ability, but it appears that what is inherited is degrees (as suggested by Yeo et al.) rather than (or as well as) direction of lateralization.

Crow, T. J.
Publication Title: 
Critical Reviews in Neurobiology

Several lines of evidence support the role of an epigenetic-induced GABAergic cortical dysfunction in schizophrenia psychopathology, which is probably dependent on an increase in the expression of DNA-methyltransferase-1 occurring selectively in GABAergic neurons. The key enzyme regulating GABA synthesis, termed glutamic acid decarboxylase 67 (GAD67) and the important neurodevelopmental protein called reelin are coexpressed in GABAergic neurons. Upon release, GABA and reelin bind to postsynaptic receptors located in dendrites, somata, or the axon initial segment of pyramidal neurons.

Costa, E.
Davis, J. M.
Dong, E.
Grayson, D. R.
Guidotti, A.
Tremolizzo, L.
Veldic, M.
Publication Title: 
Proceedings of the National Academy of Sciences of the United States of America

The polygenic nature of complex psychiatric disorders suggests a common pathway that may be involved in the down-regulation of multiple genes through an epigenetic mechanism. To investigate the role of methylation in down-regulating the expression of mRNAs that may be associated with the schizophrenia phenotype, we have adopted a cell-culture model amenable to this line of investigation.

Noh, Jai Sung
Sharma, Rajiv P.
Veldic, Marin
Salvacion, Alain A.
Jia, Xiaomei
Chen, Ying
Costa, Erminio
Guidotti, Alessandro
Grayson, Dennis R.
Publication Title: 
Journal of Neurochemistry

Glutamatergic signaling is regulated, in part, through differential expression of NMDA and AMPA/KA channel subunits and G protein-coupled metabotropic receptors. In human brain, region-specific expression patterns of glutamate receptor genes are maintained over the course of decades, suggesting a role for molecular mechanisms involved in long-term regulation of transcription, including methylation of lysine residues at histone N-terminal tails.

Stadler, Florian
Kolb, Gabriele
Rubusch, Lothar
Baker, Stephen P.
Jones, Edward G.
Akbarian, Schahram
Publication Title: 
PloS One

The role of DNA cytosine methylation, an epigenetic regulator of chromatin structure and function, during normal and pathological brain development and aging remains unclear. Here, we examined by MethyLight PCR the DNA methylation status at 50 loci, encompassing primarily 5' CpG islands of genes related to CNS growth and development, in temporal neocortex of 125 subjects ranging in age from 17 weeks of gestation to 104 years old. Two psychiatric disease cohorts--defined by chronic neurodegeneration (Alzheimer's) or lack thereof (schizophrenia)--were included.

Siegmund, Kimberly D.
Connor, Caroline M.
Campan, Mihaela
Long, Tiffany I.
Weisenberger, Daniel J.
Biniszkiewicz, Detlev
Jaenisch, Rudolf
Laird, Peter W.
Akbarian, Schahram
Publication Title: 

In this review, we discuss changes in the regulation of gene expression in the central nervous system (CNS) associated with DNA (cytosine-5) methylation, chromatin remodeling and post-translational covalent modifications of histones. During brain development, abnormal intrinsic or extrinsic cues may compromise epigenetic processes regulating neural stem cell proliferation and differentiation and thus directly or indirectly could contribute to altered epiphenotypes leading to psychiatric disorders.

Costa, Erminio
Dong, Erbo
Grayson, Dennis R.
Guidotti, Alessandro
Ruzicka, William
Veldic, Marin
Publication Title: 
European Archives of Psychiatry and Clinical Neuroscience

Kraepelin's dichotomy, manic-depressive insanity and dementia praecox, are contrasting and true endogenous disease entities which affect excitability, the fundamental property of the CNS. Kraepelin wanted to establish a valid classification and hit the extremes in brain structure and function at a time when we had no knowledge of brain dysfunction in "functional" psychoses. The aetiology is now known: the psychoses are part of human growth and maturation and might be classified according to their brain dysfunction, which is exactly what Kraepelin wanted.

Saugstad, Letten F.


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