Seizure Semiology, Neurotransmitter Receptors and Cellular-stress Responses in Pentylenetetrazole Models of Epilepsy

2009 ◽  
Vol 4 (1) ◽  
pp. 76 ◽  
Author(s):  
Hans-J Bidmon ◽  
Erwin-J Speckmann ◽  
Karl J Zilles ◽  
◽  
◽  
...  

Ongoing research has elucidated a large variety of genes, proteins and enzyme products that are affected in epilepsy. Despite the pharmacological advances achieved by the development of antiepileptic drugs, numerous patients become pharmacoresistant. Therefore, animal models addressing these complex interactions among compensatory gene-expression cascades and consecutive molecular mechanisms are still a necessity for research-based gene and pharmacotherapy. In this article, we focus on pentylenetetrazole models to study the consequences of tonic–clonic seizures. We address two complex and closely linked aspects: alterations in neurotransmission and oxidative-stress responses. Reviewing just these two aspects highlights the need for a more standardised use of animal models and methods to allow a better integration of data from different lines of research. The latter will be most applicable for the understanding of complex disease-related interactions of gene networks, proteins and enzyme products and timely, research-based development of future therapeutic options.

2020 ◽  
Vol 16 (2) ◽  
pp. 104-116
Author(s):  
Anshul Shakya ◽  
Sushil Kumar Chaudary ◽  
Debapriya Garabadu ◽  
Hans Raj Bhat ◽  
Bibhuti Bhusan Kakoti ◽  
...  

Background: Preclinical experimental models historically play a critical role in the exploration and characterization of disease pathophysiology. Further, these in-vivo and in-vitro preclinical experiments help in target identification, evaluation of novel therapeutic agents and validation of treatments. Introduction: Diabetes mellitus (DM) is a multifaceted metabolic disorder of multidimensional aetiologies with the cardinal feature of chronic hyperglycemia. To avoid or minimize late complications of diabetes and related costs, primary prevention and early treatment are therefore necessary. Due to its chronic manifestations, new treatment strategies need to be developed, because of the limited effectiveness of the current therapies. Methods: The study included electronic databases such as Pubmed, Web of Science and Scopus. The datasets were searched for entries of studies up to June, 2018. Results: A large number of in-vivo and in-vitro models have been presented for evaluating the mechanism of anti-hyperglycaemic effect of drugs in hormone-, chemically-, pathogen-induced animal models of diabetes mellitus. The advantages and limitations of each model have also been addressed in this review. Conclusion: This review encompasses the wide pathophysiological and molecular mechanisms associated with diabetes, particularly focusing on the challenges associated with the evaluation and predictive validation of these models as ideal animal models for preclinical assessments and discovering new drugs and therapeutic agents for translational application in humans. This review may further contribute to discover a novel drug to treat diabetes more efficaciously with minimum or no side effects. Furthermore, it also highlights ongoing research and considers the future perspectives in the field of diabetes.


Cells ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 1105 ◽  
Author(s):  
Kim ◽  
Lee ◽  
Seo ◽  
Kim ◽  
Kim ◽  
...  

Radiotherapy is one of the major cancer treatment strategies. Exposure to penetrating radiation causes cellular stress, directly or indirectly, due to the generation of reactive oxygen species, DNA damage, and subcellular organelle damage and autophagy. These radiation-induced damage responses cooperatively contribute to cancer cell death, but paradoxically, radiotherapy also causes the activation of damage-repair and survival signaling to alleviate radiation-induced cytotoxic effects in a small percentage of cancer cells, and these activations are responsible for tumor radio-resistance. The present study describes the molecular mechanisms responsible for radiation-induced cellular stress response and radioresistance, and the therapeutic approaches used to overcome radioresistance.


2006 ◽  
Vol 162 (1) ◽  
pp. 83-93 ◽  
Author(s):  
B VANDEWATER ◽  
M DEGRAAUW ◽  
S LEDEVEDEC ◽  
M ALDERLIESTEN

Nanomaterials ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 3161
Author(s):  
Eleonora Ferrari ◽  
Francesco Barbero ◽  
Marti Busquets-Fité ◽  
Mirita Franz-Wachtel ◽  
Heinz-R. Köhler ◽  
...  

The global economic success of man-made nanoscale materials has led to a higher production rate and diversification of emission sources in the environment. For these reasons, novel nanosafety approaches to assess the environmental impact of engineered nanomaterials are required. While studying the potential toxicity of metal nanoparticles (NPs), we realized that gold nanoparticles (AuNPs) have a growth-promoting rather than a stress-inducing effect. In this study we established stable short- and long-term exposition systems for testing plant responses to NPs. Exposure of plants to moderate concentrations of AuNPs resulted in enhanced growth of the plants with longer primary roots, more and longer lateral roots and increased rosette diameter, and reduced oxidative stress responses elicited by the immune-stimulatory PAMP flg22. Our data did not reveal any detrimental effects of AuNPs on plants but clearly showed positive effects on growth, presumably by their protective influence on oxidative stress responses. Differential transcriptomics and proteomics analyses revealed that oxidative stress responses are downregulated whereas growth-promoting genes/proteins are upregulated. These omics datasets after AuNP exposure can now be exploited to study the underlying molecular mechanisms of AuNP-induced growth-promotion.


2021 ◽  
Vol 8 ◽  
Author(s):  
Claudia Richter ◽  
Rabea Hinkel

Diabetes and the often accompanying cardiovascular diseases including cardiomyopathy represent a complex disease, that is reluctant to reveal the molecular mechanisms and underlying cellular responses. Current research projects on diabetic cardiomyopathy are predominantly based on animal models, in which there are not only obvious advantages, such as genetics that can be traced over generations and the directly measurable influence of dietary types, but also not despisable disadvantages. Thus, many studies are built up on transgenic rodent models, which are partly comparable to symptoms in humans due to their genetic alterations, but on the other hand are also under discussion regarding their clinical relevance in the translation of biomedical therapeutic approaches. Furthermore, a focus on transgenic rodent models ignores spontaneously occurring diabetes in larger mammals (such as dogs or pigs), which represent with their anatomical similarity to humans regarding their cardiovascular situation appealing models for testing translational approaches. With this in mind, we aim to shed light on the currently most popular animal models for diabetic cardiomyopathy and, by weighing the advantages and disadvantages, provide decision support for future animal experimental work in the field, hence advancing the biomedical translation of promising approaches into clinical application.


2019 ◽  
Author(s):  
Xuemei Zhang ◽  
Zihan Cheng ◽  
Kai Zhao ◽  
Renhua Li ◽  
Boru Zhou ◽  
...  

Background: NACs are one of the major transcription factor families in plants which play an important role in plant growth and development, as well as in adverse stress responses. Methods: In this study, we cloned a salt-inducible NAC transcription factor gene (NAC13) from a poplar variety 84K, followed by transforming it into both tobacco and Arabidopsis. Results: Stable expression analysis of 35S::NAC13-GFP fusion protein in Arabidopsis indicated that NAC13 was localized to the nucleus. We also obtained five transgenic tobacco lines. Evidence from morphological and physiological characterization and salt treatment analyses indicated that the transgenic tobacco enhanced salt tolerance, suggesting that NAC13 gene may function as a positive regulator in tobacco responses to salt stress. Furthermore, evidence from yeast two-hybrid screening demonstrated that NAC13 protein functions as a transcriptional activator, with an activation domain located in the C-terminal region. Discussion: NAC13 gene plays an important role in response to salt stress in tobacco. Future studies are needed to shed light on molecular mechanisms of gene regulation and gene networks related to NAC13 gene in response to salt stress, which will provide a valuable theoretical basis for forest genetic breeding and resistant breeding.


Author(s):  
Rondon Ramalho ◽  
Antônio Carlos de Abreu ◽  
Evair Moisés De Lima Santiago ◽  
Gislaine Recaldes de Abreu ◽  
Marcelo Barbosa Neves ◽  
...  

Economic and social development has essential repercussions on the health of populations, as it alters the morbidity and mortality profile and favors the increase in exposures and risks to human health, especially the risk of cancer. Cancer is considered a significant public health problem worldwide, and remains with high incidence rates, being considered a complex disease, with multifactorial causes. The permanent incidence rates of prostate cancer prove to be one of the most prevalent, considered the second most common cancer in men worldwide, and a leading cause of deaths from chronic noncommunicable diseases. Among the different types of cancer, prostate cancer has been the subject of great scientific interest. In this context, animal models are valuable for studying cancer-related aspects, the use of animal models has the potential to increase our understanding of carcinogenesis, tumor biology, and the impact of specific molecular events on tumor biology. Animal models with specific human cancer characteristics can be used to test cancer prevention and treatment strategies. In this review, we aim to show how the use of animal models as an essential tool in the study of the molecular mechanisms of carcinogenesis.


2014 ◽  
Vol 146 (5) ◽  
pp. S-501
Author(s):  
Pål Vange ◽  
Vidar Beisvag ◽  
Arnar Flatberg ◽  
Wahida Afroz ◽  
Ivar S. Nordrum ◽  
...  

Genes ◽  
2021 ◽  
Vol 12 (9) ◽  
pp. 1361
Author(s):  
Poonam Kumari ◽  
Shahriar Tarighi ◽  
Thomas Braun ◽  
Alessandro Ianni

Sirtuins are key players for maintaining cellular homeostasis and are often deregulated in different human diseases. SIRT7 is the only member of mammalian sirtuins that principally resides in the nucleolus, a nuclear compartment involved in ribosomal biogenesis, senescence, and cellular stress responses. The ablation of SIRT7 induces global genomic instability, premature ageing, metabolic dysfunctions, and reduced stress tolerance, highlighting its critical role in counteracting ageing-associated processes. In this review, we describe the molecular mechanisms employed by SIRT7 to ensure cellular and organismal integrity with particular emphasis on SIRT7-dependent regulation of nucleolar functions.


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