Can we use mice to study schizophrenia?

Canetta, Sarah; Kellendonk, Christoph

doi:10.1098/rstb.2017.0032

Cited by 20 publications

(16 citation statements)

References 61 publications

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“…Thus, stressed Mmp-9 heterozygous mice might serve as a useful model of the deficit type of schizophrenia. However, caution must be taken when considering the reliability of animal models of schizophrenia (Powell and Miyakawa, 2006; Nestler and Hyman, 2010; Young et al, 2010; Jones et al, 2011; Canetta and Kellendonk, 2018).…”

Section: Discussionmentioning

confidence: 99%

“…The utility of mouse or other animal models of schizophrenia has been debated (Powell and Miyakawa, 2006; Nestler and Hyman, 2010; Young et al, 2010; Jones et al, 2011; Canetta and Kellendonk, 2018). Nonetheless, animal models that recapitulate environmental influences (e.g., stress, drugs, infections, and socioeconomic status) on clinically identified risk-factor genes in the development of schizophrenia symptoms, including cognitive, positive, and negative symptoms, are able to provide insights into possible gene × environment interactions.…”

Section: Discussionmentioning

confidence: 99%

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Psychosocial Stress Induces Schizophrenia-Like Behavior in Mice With Reduced MMP-9 Activity

Vafadari

Mitra²,

Stefaniuk³

et al. 2019

Front. Behav. Neurosci.

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Understanding gene-environment interactions in the pathogenesis of schizophrenia remains a major research challenge. Matrix metalloproteinase-9 (MMP-9) has been previously implicated in the pathophysiology of schizophrenia. In the present study, adolescent Mmp-9 heterozygous mice, with a genetically lower level of MMP-9, were subjected to resident-intruder psychosocial stress for 3 weeks and then examined in behavioral tests that evaluated cognitive deficits and positive- and negative-like symptoms of schizophrenia. Cognitive and positive symptoms in unstressed Mmp-9 heterozygous mice were unaffected by stress exposure, whereas negative symptoms were manifested only after stress exposure. Interestingly, negative symptoms were ameliorated by treatment with the antipsychotic drug clozapine. We describe a novel gene × environment interaction mouse model of schizophrenia. Lower MMP-9 levels in the brain might be a risk factor for schizophrenia that, in combination with environmental factors (e.g., psychosocial stress), may evoke schizophrenia-like symptoms that are sensitive to antipsychotic treatment.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Psychosocial Stress Induces Schizophrenia-Like Behavior in Mice With Reduced MMP-9 Activity

Vafadari

Mitra²,

Stefaniuk³

et al. 2019

Front. Behav. Neurosci.

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“…However, for neurological disorders, the complexity of the human brain, as compared to that of a rodent or even of a non-human primate, is extreme. For neuropsychiatric disorders, such as schizophrenia, common symptoms such as paranoid delusions and auditory hallucinations are uniquely human and make interpretation of results acquired from animal models particularly challenging ( Canetta and Kellendonk, 2018 ). Although imperfect, there are multiple available models of schizophrenia ( Winship et al, 2019 ), depression ( Planchez et al, 2019 ), and other neuropsychiatric ( Nestler and Hyman, 2010 ) as well as neurodegenerative disorders ( Dawson et al, 2018 ; Carta et al, 2020 ) that, to varying degrees, possess face validity (observed characteristics/symptoms that have clinical correlates in the human patient population), construct validity (key neurobiological/pathological bases of the human disorder), and/or predictive validity (expected pharmacological response to efficacious drugs currently used to treat the human disorder).…”

Section: Discussionmentioning

confidence: 99%

Repurposing Immunomodulatory Imide Drugs (IMiDs) in Neuropsychiatric and Neurodegenerative Disorders

et al. 2021

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Neuroinflammation represents a common trait in the pathology and progression of the major psychiatric and neurodegenerative disorders. Neuropsychiatric disorders have emerged as a global crisis, affecting 1 in 4 people, while neurological disorders are the second leading cause of death in the elderly population worldwide (WHO, 2001; GBD 2016 Neurology Collaborators, 2019). However, there remains an immense deficit in availability of effective drug treatments for most neurological disorders. In fact, for disorders such as depression, placebos and behavioral therapies have equal effectiveness as antidepressants. For neurodegenerative diseases such as Parkinson’s disease and Alzheimer’s disease, drugs that can prevent, slow, or cure the disease have yet to be found. Several non-traditional avenues of drug target identification have emerged with ongoing neurological disease research to meet the need for novel and efficacious treatments. Of these novel avenues is that of neuroinflammation, which has been found to be involved in the progression and pathology of many of the leading neurological disorders. Neuroinflammation is characterized by glial inflammatory factors in certain stages of neurological disorders. Although the meta-analyses have provided evidence of genetic/proteomic upregulation of inflammatory factors in certain stages of neurological disorders. Although the mechanisms underpinning the connections between neuroinflammation and neurological disorders are unclear, and meta-analysis results have shown high sensitivity to factors such as disorder severity and sample type, there is significant evidence of neuroinflammation associations across neurological disorders. In this review, we summarize the role of neuroinflammation in psychiatric disorders such as major depressive disorder, generalized anxiety disorder, post-traumatic stress disorder, and bipolar disorder, as well as in neurodegenerative disorders, such as Parkinson’s disease and Alzheimer’s disease, and introduce current research on the potential of immunomodulatory imide drugs (IMiDs) as a new treatment strategy for these disorders.

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“…The challenges of translational research are perhaps most striking when considering disorders such as schizophrenia, where it seems difficult-though perhaps not impossibleto imagine how the aberrant psychological processing that gives rise to hallucinations and delusions could be modelled in non-human animals. This question is tackled directly by Canetta & Kellendonk [26], who assert that the historical limitations of animal models of mental health disorders in providing treatment leads have arisen because of a focus on developing models with face validity of behavioural symptoms, rather than models with construct validity of the underlying neurobiological differences contributing to altered psychological processing. By modelling potential causes of schizophrenia-genetic and environmental, including earlylife experiences-and measuring specific psychological processes, such as working memory, that have been shown to be impaired in patients with schizophrenia using translational tasks, it is possible to use the array of circuit-mapping and causal manipulations in rodents to provide insights into the clinical condition.…”

Section: Introductionmentioning

confidence: 99%

Of mice and mental health: facilitating dialogue and seeing further

Milton

Holmes

2018

Phil. Trans. R. Soc. B

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The science of mental life is critical for understanding both how we function, and impairments in our functioning. However, understanding the causal mechanisms underlying mental health disorders and developing new treatments are challenges too great to be solved by any individual approach. There is a growing awareness that translational research—from laboratory to patient and back again to animal models—will be critical for the improved understanding and treatment of mental health disorders. The motivation and intention to pursue translational approaches is therefore strong in mental health research, but critically, opportunities for interaction between basic scientists and clinicians are relatively limited, and vary depending on the institution in which researchers are working. This has promoted the development of a ‘culture gap’ between basic and clinical scientists that limits interaction and sharing of knowledge. Here, we provide 14 examples of contemporary translational research and call for an increased collaborative approach to mental health research that spans clinical diagnoses, levels of analysis and bridges between basic to clinical mental health sciences, including, but not limited to, psychology and neuroscience. What is needed is an inclusive and integrated approach, bringing together scientists working at all levels of enquiry with clinicians providing insights on what works (and what does not). To stimulate the much-needed innovation in therapeutic techniques, an analysis of component parts is critical. Our approach suggests simplifying complex behaviours into distinct psychological components. Asking collaboratively driven scientific questions about dysfunction will also benefit our fundamental understanding of mental life. This article is part of a discussion meeting issue ‘Of mice and mental health: facilitating dialogue between basic and clinical neuroscientists'.

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Can we use mice to study schizophrenia?

Cited by 20 publications

References 61 publications

Psychosocial Stress Induces Schizophrenia-Like Behavior in Mice With Reduced MMP-9 Activity

Psychosocial Stress Induces Schizophrenia-Like Behavior in Mice With Reduced MMP-9 Activity

Repurposing Immunomodulatory Imide Drugs (IMiDs) in Neuropsychiatric and Neurodegenerative Disorders

Of mice and mental health: facilitating dialogue and seeing further

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