scholarly journals Incongruence of neurophysiological manifestations as reflection of disturbances in synaptic pruning of the cortex in paranoid schizophrenia

Author(s):  
Andrei Yurevich Arkhipov ◽  
Malik Kubanichbekovich Nurbekov ◽  
Valeria Borisovna Strelets

Abstract Current study provides a comprehensive analysis of neurophysiological and molecular genetic data concerning the etiology of hallucinatory-paranoid syndrome in schizophrenia. The level of cortical excitation and inhibition was determined by analysis of event-related potential (ERP) parameters: latency and amplitude of intermediate (P200) and late (P300, N400) ERP components. The results showed the impossibility to determine the level of different cortical areas activation during perceiving stimuli of different significance in patients with hallucinatory-paranoid syndrome due to unidirectional shift of both ERP parameters to significant stimuli. The observed simultaneous increase of both amplitude and latency of these components in frontal regions is associated with an excessive number of aberrant synapses, and a decrease in the central regions is associated with synaptic deficit, this is due to disturbances in synaptic pruning of the cortex. Thus, the inhomogeneity of number and quality of synapses in central and frontal cortical areas was revealed, caused by inhomogeneity of their elimination process, which may be an essential condition for hallucinatory-paranoid syndrome emergence. An epigenetic analysis was also performed to assess the methylation level of gene expressing an extracellular matrix protein and playing a key role in neural connections distribution in ontogenesis. The detected epigenetic disorders in form of demethylation of RELN gene cause pathological synaptic pruning and elimination diversity in different brain areas.

2007 ◽  
Vol 177 (4S) ◽  
pp. 421-422
Author(s):  
Ganka Nikolova ◽  
Christian O. Twiss ◽  
Hane Lee ◽  
Nelson Stanley ◽  
Janet Sinsheimer ◽  
...  

Author(s):  
Aniel Moya-Torres ◽  
Monika Gupta ◽  
Fabian Heide ◽  
Natalie Krahn ◽  
Scott Legare ◽  
...  

Abstract The production of recombinant proteins for functional and biophysical studies, especially in the field of structural determination, still represents a challenge as high quality and quantities are needed to adequately perform experiments. This is in part solved by optimizing protein constructs and expression conditions to maximize the yields in regular flask expression systems. Still, work flow and effort can be substantial with no guarantee to obtain improvements. This study presents a combination of workflows that can be used to dramatically increase protein production and improve processing results, specifically for the extracellular matrix protein Netrin-1. This proteoglycan is an axon guidance cue which interacts with various receptors to initiate downstream signaling cascades affecting cell differentiation, proliferation, metabolism, and survival. We were able to produce large glycoprotein quantities in mammalian cells, which were engineered for protein overexpression and secretion into the media using the controlled environment provided by a hollow fiber bioreactor. Close monitoring of the internal bioreactor conditions allowed for stable production over an extended period of time. In addition to this, Netrin-1 concentrations were monitored in expression media through biolayer interferometry which allowed us to increase Netrin-1 media concentrations tenfold over our current flask systems while preserving excellent protein quality and in solution behavior. Our particular combination of genetic engineering, cell culture system, protein purification, and biophysical characterization permitted us to establish an efficient and continuous production of high-quality protein suitable for structural biology studies that can be translated to various biological systems. Key points • Hollow fiber bioreactor produces substantial yields of homogenous Netrin-1 • Biolayer interferometry allows target protein quantitation in expression media • High production yields in the bioreactor do not impair Netrin-1 proteoglycan quality Graphical abstract


2002 ◽  
Vol 267 (4) ◽  
pp. 440-446 ◽  
Author(s):  
A. Kapetanopoulos ◽  
F. Fresser ◽  
G. Millonig ◽  
Y. Shaul ◽  
G. Baier ◽  
...  

Genetics ◽  
2021 ◽  
Author(s):  
Mélissa Cizeron ◽  
Laure Granger ◽  
Hannes E BÜlow ◽  
Jean-Louis Bessereau

Abstract Heparan sulfate proteoglycans contribute to the structural organization of various neurochemical synapses. Depending on the system, their role involves either the core protein or the glycosaminoglycan chains. These linear sugar chains are extensively modified by heparan sulfate modification enzymes, resulting in highly diverse molecules. Specific modifications of glycosaminoglycan chains may thus contribute to a sugar code involved in synapse specificity. Caenorhabditis elegans is particularly useful to address this question because of the low level of genomic redundancy of these enzymes, as opposed to mammals. Here, we systematically mutated the genes encoding heparan sulfate modification enzymes in C. elegans and analyzed their impact on excitatory and inhibitory neuromuscular junctions. Using single chain antibodies that recognize different heparan sulfate modification patterns, we show in vivo that these two heparan sulfate epitopes are carried by the SDN-1 core protein, the unique C. elegans syndecan orthologue, at neuromuscular junctions. Intriguingly, these antibodies differentially bind to excitatory and inhibitory synapses, implying unique heparan sulfate modification patterns at different neuromuscular junctions. Moreover, while most enzymes are individually dispensable for proper organization of neuromuscular junctions, we show that 3-O-sulfation of SDN-1 is required to maintain wild-type levels of the extracellular matrix protein MADD-4/Punctin, a central synaptic organizer that defines the identity of excitatory and inhibitory synaptic domains at the plasma membrane of muscle cells.


1997 ◽  
Vol 16 (5) ◽  
pp. 289-292 ◽  
Author(s):  
Maureen R. Johnson ◽  
Douglas J. Wilkin ◽  
Hans L. Vos ◽  
Rosa Isela Ortiz De Luna ◽  
Anindya M. Dehejia ◽  
...  

1989 ◽  
Author(s):  
Lyndon Su ◽  
Louann W. Murray ◽  
Rodney A. White ◽  
George Kopchok ◽  
Carol Guthrie ◽  
...  

2000 ◽  
Vol 275 (6) ◽  
pp. 3999-4006 ◽  
Author(s):  
Andreas R. Klatt ◽  
D. Patric Nitsche ◽  
Birgit Kobbe ◽  
Matthias Mörgelin ◽  
Mats Paulsson ◽  
...  

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Meenalakshmi M. Mariappan

Renal hypertrophy and accumulation of extracellular matrix proteins are among cardinal manifestations of diabetic nephropathy. TGF beta system has been implicated in the pathogenesis of these manifestations. Among signaling pathways activated in the kidney in diabetes, mTOR- (mammalian target of rapamycin-)regulated pathways are pivotal in orchestrating high glucose-induced production of ECM proteins leading to functional and structural changes in the kidney culminating in adverse outcomes. Understanding signaling pathways that influence individual matrix protein expression could lead to the development of new interventional strategies. This paper will highlight some of the diverse components of the signaling network stimulated by hyperglycemia with an emphasis on extracellular matrix protein metabolism in the kidney in diabetes.


Sign in / Sign up

Export Citation Format

Share Document