scholarly journals Inhibition of BET Proteins during Adolescence Affects Prefrontal Cortical Development: Relevance to Schizophrenia

2021 ◽  
Vol 22 (16) ◽  
pp. 8710
Author(s):  
Wiktor Bilecki ◽  
Agnieszka Wawrzczak-Bargieła ◽  
Iwona Majcher-Maślanka ◽  
Magdalena Chmelova ◽  
Marzena Maćkowiak

Background: The present study investigated the role of proteins from the bromodomain and extra-terminal (BET) family in schizophrenia-like abnormalities in a neurodevelopmental model of schizophrenia induced by prenatal methylazoxymethanol (MAM) administration (MAM-E17). Methods: An inhibitor of BET proteins, JQ1, was administered during adolescence on postnatal days (P) 23–P29, and behavioural responses (sensorimotor gating, recognition memory) and prefrontal cortical (mPFC) function (long-term potentiation (LTP), molecular and proteomic analyses) studies were performed in adult males and females. Results: Deficits in sensorimotor gating and recognition memory were observed only in MAM-treated males. However, adolescent JQ1 treatment affected animals of both sexes in the control but not MAM-treated groups and reduced behavioural responses in both sexes. An electrophysiological study showed LTP impairments only in male MAM-treated animals, and JQ1 did not affect LTP in the mPFC. In contrast, MAM did not affect activity-dependent gene expression, but JQ1 altered gene expression in both sexes. A proteomic study revealed alterations in MAM-treated groups mainly in males, while JQ1 affected both sexes. Conclusions: MAM-induced schizophrenia-like abnormalities were observed only in males, while adolescent JQ1 treatment affected memory recognition and altered the molecular and proteomic landscape in the mPFC of both sexes. Thus, transient adolescent inhibition of the BET family might prompt permanent alterations in the mPFC.

Author(s):  
W. K. Jones ◽  
J. Robbins

Two myosin heavy chains (MyHC) are expressed in the mammalian heart and are differentially regulated during development. In the mouse, the α-MyHC is expressed constitutively in the atrium. At birth, the β-MyHC is downregulated and replaced by the α-MyHC, which is the sole cardiac MyHC isoform in the adult heart. We have employed transgenic and gene-targeting methodologies to study the regulation of cardiac MyHC gene expression and the functional and developmental consequences of altered α-MyHC expression in the mouse.We previously characterized an α-MyHC promoter capable of driving tissue-specific and developmentally correct expression of a CAT (chloramphenicol acetyltransferase) marker in the mouse. Tissue surveys detected a small amount of CAT activity in the lung (Fig. 1a). The results of in situ hybridization analyses indicated that the pattern of CAT transcript in the adult heart (Fig. 1b, top panel) is the same as that of α-MyHC (Fig. 1b, lower panel). The α-MyHC gene is expressed in a layer of cardiac muscle (pulmonary myocardium) associated with the pulmonary veins (Fig. 1c). These studies extend our understanding of α-MyHC expression and delimit a third cardiac compartment.


Endoscopy ◽  
2004 ◽  
Vol 36 (05) ◽  
Author(s):  
K Collins ◽  
GA Doherty ◽  
MR Sweeney ◽  
SM Byrne ◽  
AA Aftab ◽  
...  

2017 ◽  
Vol 4 (2) ◽  
Author(s):  
NEHA SINGH ◽  
INDERJEET BHOGAL ◽  
ABHISHEK KUMAR ◽  
PUNIT TYAGI ◽  
GIRIJA SIKARWAR ◽  
...  

Acclimatization is a process that occurs in individual cells to a drastic change in micro and macro environments. When an organism is subjected to a new environment or a change in its normal growing conditions, the cellular mechanisms initiate a warning sign and over a period of time or over generations the acquired, modified traits are being communicated and fixed as a new trait. If there is lack of equilibrium within the cell due to over expression of a single gene or network of associated genes either manmade or due to mutations, the organism or plant tries to fix it by initiating gene regulatory mechanisms. According to our neutral theory of gene expression, always a cell tries to maintain its pH by modifying its cytosol through altered gene expression. In the present investigation, 198 AtMYB genes were analyzed and found to play an intrinsic photosystem linked network of 38 nodes where MYB being regulated by a set of 48 miRNAs. Members of the network have evidence-based link to energy related mechanisms. Altering gene expression to an extent where, the cell may not be able to fix it or a trait, which requires excessive energy loss escorts the organism’s gene regulation by breakdown of the introduced sequence over few generations. Events with constitutive overexpression may suffer poor performance over the years based on gene network prevailing in the crop of interest. Hence, network rewiring with minimal energy expenses is concerned.


Animals ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 2273
Author(s):  
Menelaos Kavouras ◽  
Emmanouil E. Malandrakis ◽  
Ewout Blom ◽  
Kyriaki Tsilika ◽  
Theodoros Danis ◽  
...  

In farmed flatfish, such as common sole, color disturbances are common. Dyschromia is a general term that includes the color defects on the blind and ocular sides of the fish. The purpose was to examine the difference in gene expression between normal pigmented and juveniles who present ambicoloration. The analysis was carried out with next-generation sequencing techniques and de novo assembly of the transcriptome. Transcripts that showed significant differences (FDR < 0.05) in the expression between the two groups, were related to those of zebrafish (Danio rerio), functionally identified, and classified into categories of the gene ontology. The results revealed that ambicolorated juveniles exhibit a divergent function, mainly of the central nervous system at the synaptic level, as well as the ionic channels. The close association of chromophore cells with the growth of nerve cells and the nervous system was recorded. The pathway, glutamate binding–activation of AMPA and NMDA receptors–long-term stimulation of postsynaptic potential–LTP (long term potentiation)–plasticity of synapses, appears to be affected. In addition, the development of synapses also seems to be affected by the interaction of the LGI (leucine-rich glioma inactivated) protein family with the ADAM (a disintegrin and metalloprotease) ones.


2021 ◽  
pp. 117462
Author(s):  
Victor Carrasco-Navarro ◽  
Ana-Belén Muñiz González ◽  
Jouni Sorvari ◽  
Jose-Luis Martínez Guitarte

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