Gene knockout animal models of depression, anxiety and obsessive compulsive disorders

Scherma, María; Giunti, Elisa; Fratta, Walter; Fadda, Paola

doi:10.1097/ypg.0000000000000238

Cited by 17 publications

(7 citation statements)

References 92 publications

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“…Therefore, their pathogenesis has become a key research question that needs to be urgently solved. Animal models of psychiatric disorders are widely used in preclinical research on mental disorders (Scherma et al, 2019). Chronic unpredictable mild stress (CUMS) is the most commonly used rodent model of depression.…”

Section: Introductionmentioning

confidence: 99%

Depression-/Anxiety-Like Behavior Alterations in Adult Slit2 Transgenic Mice

Huang

Wang

Yan

et al. 2021

Front. Behav. Neurosci.

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Background: Slit2 is a member of the Slit family of secreted glycoproteins that plays highly conserved roles in neuronal axon guidance and cellular migration. Our previous experimental results showed Alzheimer's disease-like alterations and increased permeability of the blood–brain barrier in Slit2-overexpressing transgenic (Slit2-Tg) mice aged 8–9 months. Nevertheless, relatively little is known about behavioral alterations in adult Slit2-Tg mice (2–6 months of age). To observe the age-related behavioral effects of Slit2 overexpression in adult mice, we performed a battery of behavioral tests with adult Slit2-Tg mice at 2–6 months of age.Results: The body weight of Slit2-Tg mice was lower than that of the wild-type mice from 15 weeks of age. Compared with the control mice, depression-like behaviors were found in Slit2-Tg mice from 15 to 21 weeks of age in the sucrose preference test, although Slit2-Tg mice were hyperactive in the tail suspension test. The anxiety-like behaviors were found in Slit2-Tg mice in the open field test, as well as increased locomotor activity. The anxiety-like behaviors were also found in adult Slit2-Tg mice in the elevated plus maze. Compared to wild-type mice at 23 weeks old, impairment of the hippocampal neurons were found in Slit2-Tg mice at the same age in hematoxylin–eosin staining (H&E), including some eccentric dispersion and expansion of neuronal bodies. In addition, the messenger RNA (mRNA) expression of TNF-α was elevated in the hippocampus of adult Slit2-Tg mice.Conclusions: Slit2 overexpression causes depression-/anxiety-like behaviors in adult mice that may be related to an increase in inflammatory factors and damage to hippocampal neurons.

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Section: Introductionmentioning

confidence: 99%

Depression-/Anxiety-Like Behavior Alterations in Adult Slit2 Transgenic Mice

Huang

Wang

Yan

et al. 2021

Front. Behav. Neurosci.

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“…In depression, stress has long been considered a causal factor, but increasingly, genes that may serve as risk factors are being studied. In fact, and beyond the first attempts to mimic depression with brain lesions (e.g., olfactory bulbectomy; Wang et al, 2007 ), the most established animal models of depression recapitulate (either in isolation or in a combined mode) such processes through selective breeding (e.g., the Flinder’s sensitive line of rats; Overstreet, 1993 ) or genetic engineering (see for review Cryan and Mombereau, 2004 ; Lucki, 2011 ; Planchez et al, 2019 ; Scherma et al, 2019 ), as well as through environmental manipulations—e.g., applying chronic social ( Rygula et al, 2005 ), isolated or combined stressors ( Willner, 2005 ). In the process of internal validation, researchers developing these models have collected data demonstrating that these animals display behavioral endpoints matching the characteristics reported either in the DSM or ICD diagnostic tools as well as neurochemical and molecular features compatible we those observed in clinical settings ( Cryan and Holmes, 2005 ; Kalueff et al, 2007 ; Markou et al, 2009 ; Nestler and Hyman, 2010 ; Pollak et al, 2010 ).…”

Section: Modeling and Testing Depression In Rodentsmentioning

confidence: 99%

New Horizons for Phenotyping Behavior in Rodents: The Example of Depressive-Like Behavior

Leite‐Almeida

Castelhano-Carlos

Sousa

2022

Front. Behav. Neurosci.

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The evolution of the field of behavioral neuroscience is significantly dependent on innovative disruption triggered by our ability to model and phenotype animal models of neuropsychiatric disorders. The ability to adequately elicit and measure behavioral parameters are the fundaments on which the behavioral neuroscience community establishes the pathophysiological mechanisms of neuropsychiatric disorders as well as contributes to the development of treatment strategies for those conditions. Herein, we review how mood disorders, in particular depression, are currently modeled in rodents, focusing on the limitations of these models and particularly on the analyses of the data obtained with different behavioral tests. Finally, we propose the use of new paradigms to study behavior using multidimensional strategies that better encompasses the complexity of psychiatric conditions, namely depression; these paradigms provide holistic phenotyping that is applicable to other conditions, thus promoting the emergence of novel findings that will leverage this field.

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“…Transgenesis includes the addition of foreign genetic information to animals and specific inhibition of endogenous gene expression. The knockout animals are transgenic that have a specific interest gene disabled are transgenic, and are widely used to investigate both normal gene function, as well as the analyses of patho-biological roles of select genes involved in various disease states [21]. In addition, such transgene/knockout animal models are actively used in the development of new therapeutics and associated strategies.…”

Section: Genetically Engineered Animal Models For Drug Discoverymentioning

confidence: 99%