Animal inflammation-based models of depression and their application to drug discovery

ABSTRACT

Introduction: Depression, anxiety and other affective disorders are globally widespread and severely debilitating human brain diseases. Despite their high prevalence and mental health impact, affective pathogenesis is poorly understood, and often remains recurrent and resistant to treatment. The lack of efficient antidepressants and presently limited conceptual innovation necessitate novel approaches and new drug targets in the field of antidepressant therapy.

Areas covered: Herein, the authors discuss the emerging role of neuro-immune interactions in affective pathogenesis, which can become useful targets for CNS drug discovery, including modulating neuroinflammatory pathways to alleviate affective pathogenesis.

Expert opinion: Mounting evidence implicates microglia, polyunsaturated fatty acids (PUFAs), glucocorticoids and gut microbiota in both inflammation and depression. It is suggested that novel antidepressants can be developed based on targeting microglia-, PUFAs-, glucocorticoid- and gut microbiota-mediated cellular pathways. In addition, the authors call for a wider application of novel model organisms, such as zebrafish, in studying shared, evolutionarily conserved (and therefore, core) neuro-immune mechanisms of depression.

KEYWORDS:

• Depression
• affective disorders
• animal models
• neuroinflammation
• neuroimmune modulation
• drug discovery

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Corrigendum

Article highlights

• Affective disorders are globally widespread and severely debilitating human diseases.

• The lack of efficient antidepressants necessitates novel approaches and new drug targets

• Neuro-immune interactions play an important role in affective pathogenesis, and its experimental animal models

• Microglia, polyunsaturated fatty acids (PUFAs), glucocorticoids and gut microbiota are critical for inflammation and depression.

• Novel antidepressants can be developed based on targeting microglia-, PUFAs-, glucocorticoid- and gut microbiota-mediated cellular pathways.

• Novel model organisms, such as zebrafish, may be important models for studying neuro-immune mechanisms of depression

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Declaration of interest

L Tian is supported by the European Commission FP7/Cooperation sub-program HEALTH-2013-Innovation Grant 602919 and Magnus Ehrnrooth Foundation. C Song is supported by the National Natural Science Fund of China grants 81171118 and 81471223. AV Kalueff is supported by the Russian Foundation for Basic Research grant 16-04-00851. His research laboratories are supported by Guangdong Ocean University, St. Petersburg State University and Ural Federal University (Government of Russian Federation Act 211, contract 02-A03.21.0006). X Zhu is funded by the Fundamental Research Funds for the Central Universities of China (XDJK2016C071). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

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This manuscript has not been funded.