scholarly journals Nucleus-Specific Abnormalities of GABAergic Synaptic Transmission in a Genetic Model of Absence Seizures

2006 ◽  
Vol 96 (6) ◽  
pp. 3074-3081 ◽  
Author(s):  
Thomas Bessaïh ◽  
Laurence Bourgeais ◽  
Carmen I. Badiu ◽  
David A. Carter ◽  
Tibor I. Toth ◽  
...  
Keyword(s):  
Genetic Model ◽  
Molecular Genetic ◽  
Experimental Studies ◽  
Protein S ◽  
Absence Epilepsy ◽  
Pathophysiological Mechanism ◽  
Full Spectrum ◽  
Genetic Changes ◽  
Absence Seizures ◽  
Thalamocortical Network

Human and experimental studies indicate that molecular genetic changes in GABAA receptors may underlie the expression of spike-and-waves discharges (SWDs) occurring during absence seizures. However, the full spectrum of the genetic defects underlying these seizures has only been partially elucidated, the expression and functional profiles of putative abnormal protein(s) within the thalamocortical network are undefined, and the pathophysiological mechanism(s) by which these proteins would lead to absence paroxysms are poorly understood. Here we investigated GABAA inhibitory postsynaptic currents (IPSCs) in key thalamocortical areas, i.e., the somatosensory cortex, ventrobasal thalamus (VB) and nucleus reticularis thalami (NRT), in preseizure genetic absence epilepsy rats from Strasbourg (GAERS), a well-established genetic model of typical absence seizures that shows no additional neurological abnormalities, and compared their properties to age-matched non-epileptic controls (NECs). Miniature GABAA IPSCs of VB and cortical layers II/III neurons were similar in GAERS and NEC, whereas in GAERS NRT neurons they had 25% larger amplitude, 40% faster decay. In addition, baclofen was significantly less effective in decreasing the frequency of NRT mIPSCs in GAERS than in NEC, whereas no difference was observed for cortical and VB mIPSCS between the two strains. Paired-pulse depression was 45% smaller in GAERS NRT, but not in VB, and was insensitive to GABAB antagonists. These results point to subtle, nucleus-specific, GABAA receptor abnormalities underlying SWDs of typical absence seizures rather than a full block of these receptors across the whole thalamocortical network, and their occurrence prior to seizure onset suggests that they might be of epileptogenic significance.

scholarly journals Metabolic and molecular-genetic changes in the liver during carbon tetrachloride intoxication

2020 ◽  
Vol 99 (9) ◽  
pp. 996-1000
Author(s):  
Denis O. Karimov ◽  
Tatyana G. Kutlina ◽  
Guzel’ F. Mukhammadiyeva ◽  
Yana V. Valova ◽  
Samat S. Baygildin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Blood Serum ◽  
Pearson Correlation ◽  
Molecular Genetic ◽  
Experimental Studies ◽  
Pcr Amplification ◽  
Statistical Processing ◽  
Male Rats ◽  
Clinical Test ◽  
Genetic Changes

Introduction. Toxic hepatitis (TH) is a complex and multifaceted disease, the development of which is mediated by a complex of biochemical and molecular genetic interactions. The current understanding of the pathogenesis of TH and, as a consequence, its treatment is based on standardization of the phenotype of the disease, often without taking into account metabolic disorders within the cells. Material and methods. experimental studies were performed on white outbred male rats weighing 200-220 g. A 50% solution of TCM was used as a toxicant. Biochemical studies were performed on a laboratory medical photometer “Stat Fax 3300” using clinical test kits and control materials manufactured by Vector-Best LLC. Liver tissue for histological examination was subjected to the standard histological procedure and paraffin embedding. Sections 5-7 μm thick were stained with hematoxylin-eosin. Gene expression analysis was performed using real-time PCR amplification on a RotorGene instrument (QIAGEN). Statistical processing of experimental data was performed using the Pearson correlation coefficient and one-way analysis of variance (ANOVA). The results were considered reliable at p <0.05. Results. As a result of the analysis of the correlation of the expression of the studied genes and the level of biochemical parameters, it was found that the correlation of the expression of the Nfe2l2 and Gstm1 genes was r = 0.812 (p = 0.0001). The dynamics of gene expression of Chek, Gstm1, Gstp1, Nfe2l2, had a negative correlation with the level of AST activity in blood serum. And the expression of the genes Chek, Gclc, Gstm1, Nfe2l2, Ripk, Sod1 with an index of ALT activity in the blood serum. After 72 hours, the expression of almost all of the studied genes became multidirectional. And the correlation between indices is often not determined. An analysis of the relationship between the level of cytolysis enzymes and the correlation level of the studied genes showed that after 72 hours the correlation was observed in the Gstm1, Hmox, and Sod1 genes with the levels of AST and ALT.

Metabolic approach of absence seizures in a genetic model of absence epilepsy, the GAERS: Study of the leucine-glutamate cycle

2001 ◽  
Vol 66 (5) ◽  
pp. 923-930 ◽  
Author(s):  
Franck Dufour ◽  
Katarzyna A. Nalecz ◽  
Maciej J. Nalecz ◽  
Astrid Nehlig
Keyword(s):  
Genetic Model ◽  
Absence Epilepsy ◽  
Absence Seizures

A bigger brain for a more complex environment

2020 ◽  
Vol 31 (8) ◽  
pp. 803-816
Author(s):  
Umberto di Porzio
Keyword(s):  
Human Brain ◽  
Cognitive Abilities ◽  
Molecular Genetic ◽  
Adult Size ◽  
Genetic Changes ◽  
Cultural Challenges ◽  
Birth Canal ◽  
Newborn Brain ◽  
Neuronal Interactions ◽  
The Brain

AbstractThe environment increased complexity required more neural functions to develop in the hominin brains, and the hominins adapted to the complexity by developing a bigger brain with a greater interconnection between its parts. Thus, complex environments drove the growth of the brain. In about two million years during hominin evolution, the brain increased three folds in size, one of the largest and most complex amongst mammals, relative to body size. The size increase has led to anatomical reorganization and complex neuronal interactions in a relatively small skull. At birth, the human brain is only about 20% of its adult size. That facilitates the passage through the birth canal. Therefore, the human brain, especially cortex, develops postnatally in a rich stimulating environment with continuous brain wiring and rewiring and insertion of billions of new neurons. One of the consequence is that in the newborn brain, neuroplasticity is always turned “on” and it remains active throughout life, which gave humans the ability to adapt to complex and often hostile environments, integrate external experiences, solve problems, elaborate abstract ideas and innovative technologies, store a lot of information. Besides, hominins acquired unique abilities as music, language, and intense social cooperation. Overwhelming ecological, social, and cultural challenges have made the human brain so unique. From these events, as well as the molecular genetic changes that took place in those million years, under the pressure of natural selection, derive the distinctive cognitive abilities that have led us to complex social organizations and made our species successful.

scholarly journals Genetic Approaches Using Zebrafish to Study the Microbiota–Gut–Brain Axis in Neurological Disorders

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 566
Author(s):  
Jae-Geun Lee ◽  
Hyun-Ju Cho ◽  
Yun-Mi Jeong ◽  
Jeong-Soo Lee
Keyword(s):  
Neurological Disorders ◽  
Genetic Model ◽  
Molecular Genetic ◽  
Autism Spectrum ◽  
Behavioral Abnormalities ◽  
Bidirectional Signaling ◽  
Intestinal Dysbiosis ◽  
The Central Nervous System ◽  
The Brain

The microbiota–gut–brain axis (MGBA) is a bidirectional signaling pathway mediating the interaction of the microbiota, the intestine, and the central nervous system. While the MGBA plays a pivotal role in normal development and physiology of the nervous and gastrointestinal system of the host, its dysfunction has been strongly implicated in neurological disorders, where intestinal dysbiosis and derived metabolites cause barrier permeability defects and elicit local inflammation of the gastrointestinal tract, concomitant with increased pro-inflammatory cytokines, mobilization and infiltration of immune cells into the brain, and the dysregulated activation of the vagus nerve, culminating in neuroinflammation and neuronal dysfunction of the brain and behavioral abnormalities. In this topical review, we summarize recent findings in human and animal models regarding the roles of the MGBA in physiological and neuropathological conditions, and discuss the molecular, genetic, and neurobehavioral characteristics of zebrafish as an animal model to study the MGBA. The exploitation of zebrafish as an amenable genetic model combined with in vivo imaging capabilities and gnotobiotic approaches at the whole organism level may reveal novel mechanistic insights into microbiota–gut–brain interactions, especially in the context of neurological disorders such as autism spectrum disorder and Alzheimer’s disease.

scholarly journals Chronic Alcohol Use Induces Molecular Genetic Changes in the Dorsomedial Thalamus of People with Alcohol-Related Disorders

2021 ◽  
Vol 11 (4) ◽  
pp. 435
Author(s):  
Andreas-Christian Hade ◽  
Mari-Anne Philips ◽  
Ene Reimann ◽  
Toomas Jagomäe ◽  
Kattri-Liis Eskla ◽  
...  
Keyword(s):  
Alcohol Use ◽  
Molecular Genetic ◽  
Brain Structures ◽  
Thalamic Nuclei ◽  
Genetic Changes ◽  
Molecular Changes ◽  
Gabaergic Neurotransmission ◽  
And Control ◽  
Upregulated Genes

The Mediodorsal (MD) thalamus that represents a fundamental subcortical relay has been underrepresented in the studies focusing on the molecular changes in the brains of subjects with alcohol use disorder (AUD). In the current study, MD thalamic regions from AUD subjects and controls were analyzed with Affymetrix Clariom S human microarray. Long-term alcohol use induced a significant (FDR ≤ 0.05) upregulation of 2802 transcripts and downregulation of 1893 genes in the MD thalamus of AUD subjects. A significant upregulation of GRIN1 (glutamate receptor NMDA type 1) and FTO (alpha-ketoglutarate dependent dioxygenase) was confirmed in western blot analysis. Immunohistochemical staining revealed similar heterogenous distribution of GRIN1 in the thalamic nuclei of both AUD and control subjects. The most prevalent functional categories of upregulated genes were related to glutamatergic and GABAergic neurotransmission, cellular metabolism, and neurodevelopment. The prevalent gene cluster among down-regulated genes was immune system mediators. Forty-two differentially expressed genes, including FTO, ADH1B, DRD2, CADM2, TCF4, GCKR, DPP6, MAPT and CHRH1, have been shown to have strong associations (FDR p < 10−8) with AUD or/and alcohol use phenotypes in recent GWA studies. Despite a small number of subjects, we were able to detect robust molecular changes in the mediodorsal thalamus caused by alcohol emphasizing the importance of deeper brain structures such as diencephalon, in the development of AUD-related dysregulation of neurocircuitry.

Embracing multidimensionality in phonological analysis

2021 ◽  
Vol 38 (1) ◽  
pp. 101-139
Author(s):  
Abigail C. Cohn ◽  
Margaret E. L. Renwick
Keyword(s):  
Native Speaker ◽  
Experimental Studies ◽  
Spoken Language ◽  
Iterative Approach ◽  
Full Spectrum ◽  
Multiple Factors ◽  
Multiple Data ◽  
Language Data ◽  
Corpus Data ◽  
Insight Into

Abstract We pursue the idea, implicit in much current phonological research, that understanding the multiple factors that shape speech production and perception is within the purview of phonology. In particular, increased access to naturalistic data has highlighted the multidimensional reality of variation in spoken language. At the same time, longstanding methods of doing phonology – including impressionistic analysis, and laboratory and experimental studies – remain crucial to understanding native speaker competence and grammar. We advocate for an expanded methodological toolbox in phonological analysis, using an iterative approach that crucially includes naturalistic corpus data. Integrating across multiple data sources offers fuller insight into the nature of the phonological system and native speaker-hearer ability. Several case studies highlight findings gained through linked, iterative studies, showing the importance of naturalistic data for a richer understanding of phonological phenomena, and leading us to reflect on desiderata for corpora to reveal speaker-specific patterns in fine phonetic detail and variability, which we argue are part of a speaker-hearer’s phonological competence. Phonological analysis that embraces the full spectrum of variation in spoken language data (from categorical to gradient, and systematic to sporadic) contributes to a deeper understanding of phonology in this richer sense.

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