Animal models of major depressive disorder and the implications for drug discovery and development

Demin, Konstantin A.; Sysoev, Maksim; Chernysh, Maria V.; Savva, Anna K.; Koshiba, Mamiko; Wappler-Guzzetta, Edina A.; Song, Cai; Abreu, Murilo S. de; Leonard, Brian E.; Parker, Matthew O.; Harvey, Brian H.; Tian, Li; Vasar, Eero; Strekalova, Tatyana; Amstislavskaya, Tamara G.; Volgin, Andrey D.; Alpyshov, Erik T.; Wang, Dongmei; Kalueff, Allan V.

doi:10.1080/17460441.2019.1575360

Cited by 17 publications

(16 citation statements)

References 306 publications

(237 reference statements)

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“…The model might be particularly useful in the preclinical phase to test whether a particular drug/treatment is effective in preventing affective and behavioral changes in endotoxin-challenged healthy humans. This would nicely complement animal studies (e.g., [ 100 – 102 , 114 – 116 ]), by developing tailored therapies for patients with inflammation-associated depression, and testing them in a human population free of comorbidities and in a limited period of time.…”

Section: Experimental Endotoxemia As a Tool To Develop And Test Therapies For Inflammation-associated Depressionmentioning

confidence: 99%

Sick for science: experimental endotoxemia as a translational tool to develop and test new therapies for inflammation-associated depression

et al. 2020

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Depression is one of the global leading causes of disability, but treatments remain limited and classical antidepressants were found to be ineffective in a substantial proportion of patients. Thus, novel effective therapies for the treatment of depression are urgently needed. Given the emerging role of inflammation in the etiology and pathophysiology of affective disorders, we herein illustrate how experimental endotoxemia, a translational model of systemic inflammation, could be used as a tool to develop and test new therapeutic options against depression. Our concept is based on the striking overlap of inflammatory, neural, and affective characteristics in patients with inflammation-associated depression and in endotoxin-challenged healthy subjects. Experimental administration of endotoxin in healthy volunteers is safe, well-tolerated, and without known longterm health risks. It offers a highly standardized translational approach to characterize potential targets of therapies against inflammation-associated depression, as well as to identify characteristics of patients that would benefit from these interventions, and, therefore, could contribute to improve personalization of treatment and to increase the overall rate of responders.

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Section: Experimental Endotoxemia As a Tool To Develop And Test Therapies For Inflammation-associated Depressionmentioning

confidence: 99%

Sick for science: experimental endotoxemia as a translational tool to develop and test new therapies for inflammation-associated depression

et al. 2020

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“…In general, to better understand human emotional disorders, we may need to target not only specific individual phenotypes of interest, but also their neural aspects, such as neurochemistry or circuitry (Demin et al, ). Because no animal is a perfect replication of the human emotional landscape, not all criteria can be met by a single model of affective behavior (Demin et al, ). Thus, using a combination of different model organisms (e.g., rodents, zebrafish and crayfish) may improve our understanding of each specific emotional condition.…”

Section: Resultsmentioning

confidence: 99%

Emotional behavior in aquatic organisms? Lessons from crayfish and zebrafish

Abreu

Maximino

Banha

et al. 2019

J of Neuroscience Research

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Experimental animal models are a valuable tool to study the neurobiology of emotional behavior and mechanisms underlying human affective disorders. Mounting evidence suggests that various aquatic organisms, including both vertebrate (e.g., zebrafish) and invertebrate (e.g., crayfish) species, may be relevant to study animal emotional response and its deficits. Ideally, model organisms of disease should possess considerable genetic and physiological homology to mammals, display robust behavioral and physiological responses to stress, and should be sensitive to a wide range of drugs known to modulate stress and affective behaviors. Here, we summarize recent findings in the field of zebrafish‐ and crayfish‐based tests of stress, anxiety, aggressiveness and social preference, and discuss further perspectives of using these novel model organisms in translational biological psychiatry. Outlining the remaining questions in this field, we also emphasize the need in further development and a wider use of crayfish and zebrafish models to study the pathogenesis of affective disorders.

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“…These findings could be successfully supported in LL characterized alert behavior with Ecall and Shake as shown in our BOUQUET visualization and the reduction of higher local preference, whose meanings might be assumed as "depressive" with potential energy restriction. Animal model studies of depression have contributed to reveal pathogenesis and the development of multidirectional treatment strategies (Demin et al, 2019). Traumatic life experiences induces dysregulation in the hypothalamic-pituitary-adrenal (HPA) axis with cortisol and the locus caeruleus/norepinephrine-sympathetic nervous system (LC/NE-SNS) when the immune system activates (Pervanidou and Chrousos, 2012).…”

Section: Discussionmentioning

confidence: 99%

A Susceptible Period of Photic Day-Night Rhythm Loss in Common Marmoset Social Behavior Development

Koshiba

Watarai-Senoo

Karino

et al. 2021

Front. Behav. Neurosci.

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The prevalence of neurodevelopmental psychiatric disorders such as pervasive developmental disorders is rapidly increasing worldwide. Although these developmental disorders are known to be influenced by an individual’s genetic background, the potential biological responses to early life’s environmental exposure to both physical and psychological factors must also be considered. Many studies have acknowledged the influence of shorter time for rest at night and the simultaneous occurrence of various kinds of complications involving developmental disorders. In a prior study, we examined how a common marmoset’s (Callithrix jacchus) psychosocial development was affected when it was reared under constant daylight from birth and then reared individually by humans nursing them under constant light (LL) during their juvenile development stages. The behaviors of these marmosets were compared with those of normal day-night cycle (LD) marmosets using a multivariate analysis based on principal component analysis (PCA). That study found that LL marmosets relatively elicited egg-like calls (Ecall) and side-to-side shakes of the upper body with rapid head rotation through adulthood frequently. Based on the PCA, these behaviors were interpreted as “alert” or “hyperactive” states. However, we did not clarify susceptible periods of the photic rhythm loss experience and the psychological development output. In this study we summarize the following studies in our model animal colonies involving 30 animals (11 female, 19 males) to further explore critical age states of inquiry about each social behavior profiling. We compared social behaviors of three age stages, juvenile, adolescent and young adult equivalent to one another in four LL experience conditions, LL (postnatal day (P) 0 to around 150), Middle (P60–149, 90 days), Late (P150–239, 90 days), and LD (no experience). In the most representative 1st and 2nd principal component scores, the shifting to higher frequency of alert behaviors developed at the adult stage in LL, Middle, then Late in turn. The no LL experience group, LD, generally featured higher frequency of local preference of high position compared to LL experience present groups, in adulthood. This limited model primate study might inspire different developmental age sensitive mechanisms of neuronal network to control socio-emotional functions by utilizing the multivariate visualization method, BOUQUET. This study could potentially contribute to nurturing educational designs for social developmental disorders.

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Animal models of major depressive disorder and the implications for drug discovery and development

Cited by 17 publications

References 306 publications

Sick for science: experimental endotoxemia as a translational tool to develop and test new therapies for inflammation-associated depression

Sick for science: experimental endotoxemia as a translational tool to develop and test new therapies for inflammation-associated depression

Emotional behavior in aquatic organisms? Lessons from crayfish and zebrafish

A Susceptible Period of Photic Day-Night Rhythm Loss in Common Marmoset Social Behavior Development

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