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      Antidepressant effect of recombinant NT4-NAP/AAV on social isolated mice through intranasal route

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          Abstract

          The purpose of the present study was to observe the depression-like behavior induced by social isolation; detect the antidepressant effect of a recombinant adeno-associated virus (AAV) expressing NAP on social isolation mice by intranasal delivery. After construction of NT4-NAP/AAV, expression of NAP was confirmed in vitro. 3-week-old C57/BL mice were bred individually in cages as social isolation-rearing. Six weeks later, the first subset of mice underwent behavioral tests and western blot; the second was for enzyme-linked immunosorbent assay. NT4-NAP/AAV was delivered quaque die by nasal administration for consecutive 10 days before behavioral test. Several depression-like behaviors were observed in social isolation mice, including decreased relative sucrose preference, longer immobility time in forced swimming test, lower plasma corticosterone and decreased brain-derived neurotrophic factor in hippocampus. Thus, social isolation procedure appears to be an animal model of depression with good face and construct validity. What's more, the antidepressant effect in social isolation-rearing mice was observed after intranasal administration of NT4-NAP/AAV, suggesting that this might be a promising therapeutic strategy for depressive disorder.

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          Validity, reliability and utility of the chronic mild stress model of depression: a 10-year review and evaluation.

          This paper evaluates the validity, reliability and utility of the chronic mild stress (CMS) model of depression. In the CMS model, rats or mice are exposed sequentially, over a period of weeks, to a variety of mild stressors, and the measure most commonly used to track the effects is a decrease in consumption of a palatable sweet solution. The model has good predictive validity (behavioural changes are reversed by chronic treatment with a wide variety of antidepressants), face validity (almost all demonstrable symptoms of depression have been demonstrated), and construct validity (CMS causes a generalized decrease in responsiveness to rewards, comparable to anhedonia, the core symptom of the melancholic subtype of major depressive disorder). Overall, the CMS procedure appears to be at least as valid as any other animal model of depression. The procedure does, however, have two major drawbacks. One is the practical difficulty of carrying out CMS experiments, which are labour intensive, demanding of space, and of long duration. The other is that, while the procedure operates reliably in many laboratories, it can be difficult to establish, for reasons which remain unclear. However, once established, the CMS model can be used to study problems that are extremely difficult to address by other means.
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            Depression and hypothalamic-pituitary-adrenal activation: a quantitative summary of four decades of research.

            To summarize quantitatively the literature comparing hypothalamic-pituitary-adrenal (HPA) axis function between depressed and nondepressed individuals and to describe the important sources of variability in this literature. These sources include methodological differences between studies, as well as demographic or clinical differences between depressed samples.
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              Behavioural and neurochemical effects of post-weaning social isolation in rodents-relevance to developmental neuropsychiatric disorders.

              Exposing mammals to early-life adverse events, including maternal separation or social isolation, profoundly affects brain development and adult behaviour and may contribute to the occurrence of psychiatric disorders, such as depression and schizophrenia in genetically predisposed humans. The molecular mechanisms underlying these environmentally induced developmental adaptations are unclear and best evaluated in animal paradigms with translational salience. Rearing rat pups from weaning in isolation, to prevent social contact with conspecifics, produces reproducible, long-term changes including; neophobia, impaired sensorimotor gating, aggression, cognitive rigidity, reduced prefrontal cortical volume and decreased cortical and hippocampal synaptic plasticity. These alterations are associated with hyperfunction of mesolimbic dopaminergic systems, enhanced presynaptic dopamine (DA) and serotonergic (5-HT) function in the nucleus accumbens (NAcc), hypofunction of mesocortical DA and attenuated 5-HT function in the prefrontal cortex and hippocampus. These behavioural, morphological and neurochemical abnormalities, as reviewed herein, strongly resemble core features of schizophrenia. Therefore unravelling the mechanisms that trigger these sequelae will improve our knowledge of the aetiology of neurodevelopmental psychiatric disorders, enable identification of longitudinal biomarkers of dysfunction and permit predictive screening for novel compounds with potential antipsychotic efficacy.
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                Author and article information

                Journal
                Oncotarget
                Oncotarget
                Oncotarget
                ImpactJ
                Oncotarget
                Impact Journals LLC
                1949-2553
                7 February 2017
                29 December 2016
                : 8
                : 6
                : 10103-10113
                Affiliations
                1 College of Medicine & Forensics, Xi’an Jiaotong University Health Science Center, Xi’an, 710061, Shaanxi, PR China
                2 Clinical Research Center of Shaanxi Province for Dental and Maxillofacial Diseases, College of Stomatology, Xi'an Jiaotong University, Xi'an, 710004, PR China
                3 Sun Yat-sen University Cancer Center, Guangzhou, 510060, PR China
                4 Department of Psychiatry, First Affiliated Hospital of Xi’an Jiaotong University Health Science Center, Xi’an, 710061, Shaanxi, PR China
                5 Key Laboratory of the Health Ministry for Forensic Medicine, Xi'an Jiaotong University Health Science Center, Xi’an 710061, Shaanxi, PR China
                6 Key Laboratory of Forensic Medicine of Shaanxi Province, Xi’an Jiaotong University Health Science Center, Xi’an 710061, Shaanxi, PR China
                Author notes
                Correspondence to: Yong-hui Dang, psydyh@ 123456mail.xjtu.edu.cn
                Article
                14356
                10.18632/oncotarget.14356
                5354645
                28052034
                a1bbba78-de22-4886-9192-2f53b03bf46c
                Copyright: © 2017 Liu et al.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 9 October 2016
                : 13 December 2016
                Categories
                Research Paper

                Oncology & Radiotherapy
                social isolation,depression,nt4-nap/aav,intranasal administration,antidepressant

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