Cognitive Deficits in Schizophrenia and Other Neuropsychiatric Disorders: Convergence of Preclinical and Clinical Evidence

Stuchlı́k, Aleš; Sumiyoshi, Tomiki

doi:10.3389/fnbeh.2014.00444

Cited by 17 publications

(16 citation statements)

References 27 publications

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“…The protocol that was used in the present study was adapted from a previous study (Vogel-Ciernia and Wood, 2014). The novel object recognition test and its variations have been used to assess cognitive symptoms in rodent models of schizophrenia (Jones et al, 2011; Stuchlik and Sumiyoshi, 2014; Grayson et al, 2015). The mice were placed in an open field apparatus with ~50 lux illumination and allowed free exploration for 10 min.…”

Section: Methodsmentioning

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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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: Methodsmentioning

confidence: 99%

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

Vafadari

Mitra²,

Stefaniuk³

et al. 2019

Front. Behav. Neurosci.

View full text Add to dashboard Cite

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“…Moreover, patients with depression, but also autism, schizophrenia, and bipolar disorder, withdraw social interactions and, intriguingly, pilocarpine‐treated mice appear socially aversive . Although the range of cognitive problems can vary, disrupted learning, attention, working, spatial, and visual and contextual fear memory accompany most brain disorders . In epilepsy, the origin of cognitive comorbidities is still uncertain.…”

Section: Introductionmentioning

confidence: 99%

6 Hz corneal kindling in mice triggers neurobehavioral comorbidities accompanied by relevant changes in c‐Fos immunoreactivity throughout the brain

et al. 2017

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SummaryObjective: Besides seizures, patients with epilepsy are affected by a variety of cognitive and psychiatric comorbidities that further impair their quality of life. The present study provides an in-depth characterization of the behavioral alterations induced by 6 Hz corneal kindling. Furthermore, we correlate these behavioral changes to alterations in c-Fos protein expression throughout the brain following kindling. Methods: Adolescent male Naval Medical Research Institute (NMRI) mice were kindled via repetitive subconvulsive 6 Hz corneal stimulations until they reached the fully kindled state (defined as 10 consecutive generalized seizures). Afterwards we performed an elaborate battery of behavioral tests and we evaluated cFos expression throughout the brain using immunohistochemistry. Results: Fully kindled mice display an abnormal behavioral phenotype, characterized by basal and amphetamine-induced hyperlocomotion, anhedonia, social withdrawal, and deficits in short-and long-term memory. Moreover, 6 Hz corneal kindling enhances c-Fos immunoreactivity in the visual, parahippocampal, and motor cortices and the limbic system, whereas c-Fos + cells are decreased in the orbital cortex of fully kindled mice. Significance: The behavioral outcomes of 6 Hz corneal kindling cluster into 3 main categories: positive symptoms, negative symptoms, and cognitive impairment. These symptoms are accompanied by c-Fos activation in relevant brain regions once the fully kindled state is established. Based on the face validity of this model, we speculate that 6 Hz corneal kindling can be used to model not only pharmacoresistant limbic seizures, but also several neurobehavioral comorbidities that affect patients with epilepsy.

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“…By affecting patients' daily function, sociability, and long-term outcome, cognitive impairments place important socioeconomic burdens on society and patients themselves, also posing significant challenges to healthcare practitioners [23]. As Cohen and Weinstein point out, understanding how different cannabinoids may modulate cognitive processes can shed new light into the neurobiological mechanisms that increase the risk of long-lasting cognitive impairments in regular cannabis users.…”

mentioning

confidence: 99%

“…As Cohen and Weinstein point out, understanding how different cannabinoids may modulate cognitive processes can shed new light into the neurobiological mechanisms that increase the risk of long-lasting cognitive impairments in regular cannabis users. Moreover, cannabis use can increase the risk of developing disabling neuropsychiatric disorders, such as psychosis [24], and cognitive dysfunction is a core feature of such disorders [23]. Interestingly, endocannabinoid alterations have been implied in the pathophysiology of psychosis, independent of cannabis use [25].…”

mentioning

confidence: 99%

Cannabis and Cognition: Connecting the Dots towards the Understanding of the Relationship

2020

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Several studies have advanced the understanding of the effects of cannabis on cognitive function. A comprehensive reappraisal of such literature may help in drawing conclusions about the potential risks associated with cannabis use. In summary, the evidence suggests that earlier age of use, high-frequency and high-potency cannabis use, as well as sustained use over time and use of synthetic cannabinoids, are all correlated with a higher likelihood of developing potentially severe and persistent executive function impairments. While the exact mechanisms underlying the adverse effects of cannabis on cognition are not completely clear, Magnetic Resonance Imaging (MRI) studies support the presence of both structural and functional alterations associated with cannabis use. Cognitive dysfunction is also a core feature of many neuropsychiatric disorders and care must be taken regarding the effects of cannabis use in these patient populations. Cognitive impairments affect patients’ daily functions, sociability, and long-term outcome, posing elevated economic, social, and clinical burdens. There is, thus, a compelling case for implementing behavioral and cognitive rehabilitation therapies for these patients, as well as investigating the endocannabinoid system in the development of new psychopharmacological treatments.

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Cognitive Deficits in Schizophrenia and Other Neuropsychiatric Disorders: Convergence of Preclinical and Clinical Evidence

Cited by 17 publications

References 27 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

6 Hz corneal kindling in mice triggers neurobehavioral comorbidities accompanied by relevant changes in c‐Fos immunoreactivity throughout the brain

Cannabis and Cognition: Connecting the Dots towards the Understanding of the Relationship

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