scholarly journals Zebrafish Bioassay for Screening Therapeutic Candidates Based on Melanotrophic Activity

2021 ◽  
Vol 22 (17) ◽  
pp. 9313
Author(s):  
Ted I. Hong ◽  
Kyu-Seok Hwang ◽  
Tae-Ik Choi ◽  
Gunnar Kleinau ◽  
Patrick Scheerer ◽  
...  
Keyword(s):  
Animal Model ◽  
Skin Pigmentation ◽  
Autism Spectrum ◽  
Synthetic Analogue ◽  
Human Form ◽  
Model Studies ◽  
Melanocyte Stimulating Hormone ◽  
Physiological Processes ◽  
Skin Physiology ◽  
Novel Drug

In this study, we used the zebrafish animal model to establish a bioassay by which physiological efficacy differential of alpha-melanocyte-stimulating hormone (α-MSH) analogues could be measured by melanosome dispersion in zebrafish larvae. Brain-skin connection research has purported the interconnectedness between the nervous system and skin physiology. Accordingly, the neuropeptide α-MSH is a key regulator in several physiological processes, such as skin pigmentation in fish. In mammals, α-MSH has been found to regulate motivated behavior, appetite, and emotion, including stimulation of satiety and anxiety. Several clinical and animal model studies of autism spectrum disorder (ASD) have already demonstrated the effectiveness of α-MSH in restoring the social deficits of autism. Therefore, we sought to analyze the effect of synthetic and naturally-occurring α-MSH variants amongst different species. Our results showed that unique α-MSH derivatives from several fish species produced differential effects on the degree of melanophore dispersion. Using α-MSH human form as a standard, we could identify derivatives that induced greater physiological effects; particularly, the synthetic analogue melanotan-II (MT-II) exhibited a higher capacity for melanophore dispersion than human α-MSH. This was consistent with previous findings in an ASD mouse model demonstrating the effectiveness of MT-II in improving ASD behavioral symptoms. Thus, the melanophore assay may serve as a useful screening tool for therapeutic candidates for novel drug discovery.

“In vitro” and in Animal Model Studies on a Double Virus- Inactivated Factor VIII Concentrate

1995 ◽  
Vol 74 (03) ◽  
pp. 868-873 ◽  
Author(s):  
Silvana Arrighi ◽  
Roberta Rossi ◽  
Maria Giuseppina Borri ◽  
Vladimir Lesnikov ◽  
Marina Lesnikov ◽  
...  
Keyword(s):  
Heat Treatment ◽  
Animal Model ◽  
Factor Viii ◽  
Hepatitis A ◽  
Hepatitis A Virus ◽  
Virus Inactivation ◽  
Enveloped Viruses ◽  
Model Studies ◽  
Heat Treated

SummaryTo improve the safety of plasma derived factor VIII (FVIII) concentrate, we introduced a final super heat treatment (100° C for 30 min) as additional virus inactivation step applied to a lyophilized, highly purified FVIII concentrate (100 IU/mg of proteins) already virus inactivated using the solvent/detergent (SID) method during the manufacturing process.The efficiency of the super heat treatment was demonstrated in inactivating two non-lipid enveloped viruses (Hepatitis A virus and Poliovirus 1). The loss of FVIII procoagulant activity during the super heat treatment was of about 15%, estimated both by clotting and chromogenic assays. No substantial changes were observed in physical, biochemical and immunological characteristics of the heat treated FVIII concentrate in comparison with those of the FVIII before heat treatment.

scholarly journals An intermediate animal model of spinal cord stimulation

2016 ◽  
Vol 26 (2) ◽  
Author(s):  
Thomas Guiho ◽  
Christine Azevedo Coste ◽  
Claire Delleci ◽  
Jean-Patrick Chenu ◽  
Jean-Rodolphe Vignes ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Animal Model ◽  
Spinal Cord Stimulation ◽  
Spinal Cord Injuries ◽  
Large Animal Model ◽  
Large Animal ◽  
Physiological Processes ◽  
Spinal Roots ◽  
And Control ◽  
Stimulation Of

Spinal cord injuries (SCI) result in the loss of movement and sensory feedback as well as organs dysfunctions. For example, nearly all SCI subjects loose their bladder control and are prone to kidney failure if they do not proceed to intermittent (self-) catheterization. Electrical stimulation of the sacral spinal roots with an implantable neuroprosthesis is a promising approach, with commercialized products, to restore continence and control micturition. However, many persons do not ask for this intervention since a surgical deafferentation is needed and the loss of sensory functions and reflexes become serious side effects of this procedure. Recent results renewed interest in spinal cord stimulation. Stimulation of existing pre-cabled neural networks involved in physiological processes regulation is suspected to enable synergic recruitment of spinal fibers. The development of direct spinal stimulation strategies aiming at bladder and bowel functions restoration would therefore appear as a credible alternative to existent solutions. However, a lack of suitable large animal model complicates these kinds of studies. In this article, we propose a new animal model of spinal stimulation -pig- and will briefly introduce results from one first acute experimental validation session.

scholarly journals CK1α ablation in keratinocytes induces p53-dependent, sunburn-protective skin hyperpigmentation

2017 ◽  
Vol 114 (38) ◽  
pp. E8035-E8044 ◽  
Author(s):  
Chung-Hsing Chang ◽  
Che-Jung Kuo ◽  
Takamichi Ito ◽  
Yu-Ya Su ◽  
Si-Tse Jiang ◽  
...  
Keyword(s):  
Target Genes ◽  
Neutralizing Antibody ◽  
Double Knockout ◽  
Melanocyte Stimulating Hormone ◽  
Kit Ligand ◽  
Skin Physiology ◽  
P53 Activation ◽  
P53 Target Genes ◽  
Single Knockout

Casein kinase 1α (CK1α), a component of the β-catenin destruction complex, is a critical regulator of Wnt signaling; its ablation induces both Wnt and p53 activation. To characterize the role of CK1α (encoded byCsnk1a1) in skin physiology, we crossed mice harboring floxedCsnk1a1with mice expressing K14–Cre–ERT2to generate mice in which tamoxifen induces the deletion ofCsnk1a1exclusively in keratinocytes [single-knockout (SKO) mice]. As expected, CK1α loss was accompanied by β-catenin and p53 stabilization, with the preferential induction of p53 target genes, but phenotypically most striking was hyperpigmentation of the skin, importantly without tumorigenesis, for at least 9 mo afterCsnk1a1ablation. The number of epidermal melanocytes and eumelanin levels were dramatically increased in SKO mice. To clarify the putative role of p53 in epidermal hyperpigmentation, we established K14–Cre–ERT2CK1α/p53 double-knockout (DKO) mice and found that coablation failed to induce epidermal hyperpigmentation, demonstrating that it was p53-dependent. Transcriptome analysis of the epidermis revealed p53-dependent up-regulation of Kit ligand (KitL). SKO mice treated with ACK2 (a Kit-neutralizing antibody) or imatinib (a Kit inhibitor) abrogated the CK1α ablation-induced hyperpigmentation, demonstrating that it requires the KitL/Kit pathway. Pro-opiomelanocortin (POMC), a precursor of α-melanocyte–stimulating hormone (α-MSH), was not activated in the CK1α ablation-induced hyperpigmentation, which is in contrast to the mechanism of p53-dependent UV tanning. Nevertheless, acute sunburn effects were successfully prevented in the hyperpigmented skin of SKO mice. CK1α inhibition induces skin-protective eumelanin but no carcinogenic pheomelanin and may therefore constitute an effective strategy for safely increasing eumelanin via UV-independent pathways, protecting against acute sunburn.

scholarly journals Alterations of the endocannabinoid system and its therapeutic potential in autism spectrum disorder

Open Biology ◽  
2021 ◽  
Vol 11 (2) ◽  
Author(s):  
Mingyang Zou ◽  
Yu Liu ◽  
Shu Xie ◽  
Luxi Wang ◽  
Dexin Li ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Animal Model ◽  
Social Preference ◽  
Therapeutic Potential ◽  
Hydrolytic Enzyme ◽  
Endocannabinoid System ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Autistic Children ◽  
Novel Approach

Autism spectrum disorder (ASD) is a group of developmental disabilities, the aetiology of which remains elusive. The endocannabinoid (eCB) system modulates neurotransmission and neuronal plasticity. Evidence points to the involvement of this neuromodulatory system in the pathophysiology of ASD. We investigated whether there is a disruption to the eCB system in ASD and whether pharmacological modulation of the eCB system might offer therapeutic potential. We examined three major components of the eCB system—endogenous cannabinoids, their receptors and associated enzymes—in ASD children as well as in the valproic acid (VPA) induced animal model in autism. Furthermore, we specifically increased 2-arachidonoylglycerol (2-AG) levels by administering JZL184, a selective inhibitor of monoacylglycerol lipase which is the hydrolytic enzyme for 2-AG, to examine ASD-like behaviours in VPA-induced rats. Results showed that autistic children and VPA-induced rats exhibited reduced eCB content, increased degradation of enzymes and upregulation of CBRs. We found that repetitive and stereotypical behaviours, hyperactivity, sociability, social preference and cognitive functioning improved after acute and chronic JZL184 treatment. The major efficacy of JZL184 was observed after administration of a dosage regimen of 3 mg kg −1 , which affected both the eCB system and ASD-like behaviours. In conclusion, a reduced eCB signalling was observed in autistic children and in the ASD animal model, and boosting 2-AG could ameliorate ASD-like phenotypes in animals. Collectively, the results suggested a novel approach to ASD treatment.

scholarly journals Using Connectivity to Explain Autism

2019 ◽  
Author(s):  
Jack Adamek ◽  
Yu Luo ◽  
Joshua Ewen
Keyword(s):  
Scientific Explanation ◽  
Causal Explanation ◽  
Autism Spectrum ◽  
Imaging Method ◽  
Imaging Data ◽  
Reverse Engineer ◽  
Physiological Processes ◽  
The Mind ◽  
The Brain

The chapters in this Handbook reveal the breadth of brilliant imaging and analysis techniques designed to fulfill the mandate of cognitive neuroscience: to understand how anatomical structures and physiological processes in the brain cause typical and atypical behavior. Yet merely producing data from the latest imaging method is insufficient to truly achieve this goal. We also need a mental toolbox that contains methods of inference that allow us to derive true scientific explanation from these data. Causal inference is not easy in the human brain, where we are limited primarily to observational data and our methods of experimental perturbation in the service of causal explanation are limited. As a case study, we reverse engineer one of the most influential accounts of a neuropsychiatric disorder that is derived from observational imaging data: the connectivity theories of autism spectrum disorder (ASD). We take readers through an approach of first considering all possible causal paths that are allowed by preliminary imaging-behavioral correlations. By progressively sharpening the specificity of the measures and brain/behavioral constructs, we iteratively chip away at this space of allowable causal paths, like the sculptor chipping away the excess marble to reveal the statue. To assist in this process, we consider how current imaging methods that are lumped together under the rubric of “connectivity” may actually offer a differentiated set of connectivity constructs that can more specifically relate notions of information transmission in the mind to the physiology of the brain.

Behavioural and neuroendocrine effects of environmental background colour and social interaction in Arctic charr (Salvelinus alpinus)

2002 ◽  
Vol 205 (16) ◽  
pp. 2535-2543 ◽  
Author(s):  
Erik Höglund ◽  
Paul H. M. Balm ◽  
Svante Winberg
Keyword(s):  
Social Interaction ◽  
Salvelinus Alpinus ◽  
Arctic Charr ◽  
Skin Pigmentation ◽  
White Background ◽  
Melanocyte Stimulating Hormone ◽  
Black Background ◽  
Social Signal ◽  
Social Subordination ◽  
Colour Skin

SUMMARYIn salmonid fish, a darker skin colour has been suggested to signal social subordination. Substratum colour is another factor affecting skin pigmentation in fish; in the present experiment, juvenile Arctic charr (Salvelinus alpinus) were acclimated and allowed to interact in pairs for 5 days on a pale or dark background colour. Skin darkness was quantified prior to and following social interaction. Furthermore, agonistic behaviour and skin darkness were quantified, together with plasma levels of cortisol,adrenocorticotropin (ACTH) and α-melanocyte-stimulating hormone(α-MSH), and brain levels of monoamines and monoamine metabolites. The results show that fish interacting on a white background were more aggressive than those interacting on a black background. Social subordination resulted in skin darkening in fish kept on a white background, but not in fish kept on a black background. Furthermore, subordinate fish on a white background showed an elevation of brain norepinephric activity, an effect not seen in subordinate fish on a black background. Subordinate fish on both white and black backgrounds showed a similar activation of the brain serotonergic system and the hypothalamic—pituitary—interrenal axis. These results support the suggestion that skin darkening in subordinates acts as a social signal announcing social submission.

scholarly journals CGSEA: A Flexible Tool for Evaluating the Associations of Chemicals with Complex Diseases

2020 ◽  
Vol 10 (3) ◽  
pp. 945-949
Author(s):  
Shiqiang Cheng ◽  
Mei Ma ◽  
Lu Zhang ◽  
Li Liu ◽  
Bolun Cheng ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Expression Profiles ◽  
Association Studies ◽  
Complex Diseases ◽  
Autism Spectrum ◽  
Flexible Tool ◽  
Physiological Processes ◽  
Genome Wide ◽  
Level Data

The etiology of many human complex diseases or traits involves interactions between chemicals and genes that regulate important physiological processes. It has been well documented that chemicals can contribute to disease development through affecting gene expression in vivo. In this study, we developed a flexible tool CGSEA for scanning the candidate chemicals associated with complex diseases or traits. CGSEA only need genome-wide summary level data, such as transcriptome-wide association studies (TWAS) and mRNA expression profiles. CGSEA was applied to the GWAS summaries of attention deficiency/hyperactive disorder, (ADHD), autism spectrum disorder (ASD) and cervical cancer. CGSEA identified several significant chemicals, which have been demonstrated to be involved in the development or treatment of ADHD, ASD and cervical cancer. The CGSEA program and user manual are available at https://github.com/ChengSQXJTU/CGSEA.

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