An Overview of Animal Models Related to Schizophrenia

Winship, Ian R.; Dursun, Serdar; Baker, Glen B.; Balista, Priscila Alves; Kandratavicius, Ludmyla; Maia‐de‐Oliveira, João Paulo; Hallak, Jaime E. C.; Howland, John G.

doi:10.1177/0706743718773728

Cited by 183 publications

(114 citation statements)

References 179 publications

(249 reference statements)

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“…On the other hand, pinpointing prognostic biomarkers, that can predict the future risk of developing schizophrenia before the onset of disease symptoms, is of critical importance. This is not convenient and time-efficient in human studies and, therefore, developmental animal models are required, through which the effects of perinatal and/or early postnatal exposure to environmental manipulations and/or drug administration are investigated in peripheral tissues over the course of development [165]. Our literature search for these types of studies returned only one result, in which pregnant mice were treated with the toxicant bisphenol A (BPA), that disturbs neurodevelopment with long-term effects on behavior, and the offspring went through gene expression and DNA methylation analyses in the hippocampus and blood.…”

Section: Discussion and Perspectivesmentioning

confidence: 99%

Epigenomic Dysregulation in Schizophrenia: In Search of Disease Etiology and Biomarkers

Khavari

Cairns

2020

Cells

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Schizophrenia is a severe psychiatric disorder with a complex array of signs and symptoms that causes very significant disability in young people. While schizophrenia has a strong genetic component, with heritability around 80%, there is also a very significant range of environmental exposures and stressors that have been implicated in disease development and neuropathology, such as maternal immune infection, obstetric complications, childhood trauma and cannabis exposure. It is postulated that epigenetic factors, as well as regulatory non-coding RNAs, mediate the effects of these environmental stressors. In this review, we explore the most well-known epigenetic marks, including DNA methylation and histone modification, along with emerging RNA mediators of epigenomic state, including miRNAs and lncRNAs, and discuss their collective potential for involvement in the pathophysiology of schizophrenia implicated through the postmortem analysis of brain tissue. Given that peripheral tissues, such as blood, saliva, and olfactory epithelium have the same genetic composition and are exposed to many of the same environmental exposures, we also examine some studies supporting the application of peripheral tissues for epigenomic biomarker discovery in schizophrenia. Finally, we provide some perspective on how these biomarkers may be utilized to capture a signature of past events that informs future treatment.

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Section: Discussion and Perspectivesmentioning

confidence: 99%

Epigenomic Dysregulation in Schizophrenia: In Search of Disease Etiology and Biomarkers

Khavari

Cairns

2020

Cells

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“…The interaction of each of the products derived from G. glauca with MK-801 was also evaluated; this noncompetitive antagonist of NMDA has become a useful tool in exploring the participation of the glutamatergic system in schizophrenia [34]. Administration of MK-801 (0.5 mg/kg) for 28 days induced hypolocomotion in mice, which was measured for 30 min in the OFT, since the parameters of total crossings and rearings were lower than those of healthy animals.…”

Section: Discussionmentioning

confidence: 99%

Galphimia glauca and Natural Galphimines Block Schizophrenia-Like Symptoms Induced with Apomorphine and MK-801 in Mice

Santillán-Urquiza

Herrera-Ruíz

Zamilpa

et al. 2019

Evidence-Based Complementary and Alternative Medicine

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Background. Galphimia glauca has been used for many years in Mexican Traditional Medicine to calm “insane people.” Triterpenes, known as galphimines, were identified in this species. One of them, Galphimine-B (G-B), acts selectively on dopaminergic neurons by antagonizing the effect of glutamate on NMDA receptors. The objective of this study was to evaluate the effect of G. glauca methanolic extract (GgMeOH), a Galphimine-Rich Fraction (GRF), as well as the galphimines G-A, G-B, and G-E, on the acute psychosis induced by Apomorphine (APO) in mice and on schizophrenia-like symptoms induced by subchronic administration of MK-801. Method. On the first day, ICR male mice were given GgMeOH, GRF, or one of the galphimines. On day two, animals were treated with APO, and on day 3, they were subjected to behavioral tests. In a second test, MK-801 was administered daily for 28 days. In this case, animals were treated daily with G. glauca products from day 9 to day 28 and then subjected to behavioral tests (passive avoidance test, open field test, forced swimming test, and social interaction test). Results. The increased number of stereotyped behaviors and grooming behaviors induced with APO were counteracted by all of the experimental treatments. MK-801 induced an increase in immobility time, which was blocked with G-B; GRF counteracted the decreased social interaction, and GgMeOH and GRF prevented the memory loss induced by MK-801. Conclusion. G. glauca and their derivatives products (GRF and galphimines) were able to interact with the dopaminergic and glutamatergic drugs and to block different behaviors associated with some of the positive, negative, and cognitive symptoms of induced schizophrenia in mice. It is necessary to continue with this research, in order to identify their mechanism of action.

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“…Moreover, disruptions of myelin formation and dendritic spines have been found in patients with schizophrenia (see Meyer and Louilot, 2014;Tagliabue et al, 2017 for discussion). In other respects, the behavioural index chosen in the present study, namely locomotor activity, is often proposed to have translational relevance for psychotic symptoms in humans, given the increase in locomotor activity observed in rodents and the appearance of positive symptoms in humans after administration of NMDA antagonists or other psychotomimetic drugs (Jones et al, 2011;Winship et al, 2019). Changes in locomotor activity and DA levels in the core subregion of the Nacc were monitored in parallel, in freely moving rats, using in vivo voltammetry in adult animals.…”

Section: Introductionmentioning

confidence: 99%

Postnatal functional inactivation of the ventral subiculum enhances dopaminergic responses in the core part of the nucleus accumbens following ketamine injection in adult rats

Saoud

Beus

Eybrard

et al. 2020

Neurochemistry International

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For almost two decades schizophrenia has been considered to be a functional disconnection disorder. This functional disconnectivity between several brain regions could have a neurodevelopmental origin. Various approaches suggest the ventral subiculum (SUB) is a particular target region for neurodevelopemental disturbances in schizophrenia. It is also commonly acknowledged that there is a striatal dopaminergic (DA) dysregulation in schizophrenia which may depend on a subiculo-striatal disconnection involving glutamatergic NMDA receptors. The present study was designed to investigate, in adult rats, the effects of the non-competitive NMDA receptor antagonist ketamine on DA responses in the ventral striatum, or, more specifically, the core part of the nucleus accumbens (Nacc), following postnatal functional inactivation of the SUB. Functional inactivation of the left SUB was carried out by local tetrodotoxin (TTX) microinjection at postnatal day 8 (PND8), i.e. at a critical point in the neurodevelopmental period. DA variations were recorded using in vivo voltammetry in freely moving adult rats (11 weeks). Locomotor activity was recorded simultaneously with the extracellular levels of DA in the core part of the Nacc. Data obtained during the present study showed that after administration of ketamine, the two indexes were higher in TTX animals than PBS animals, the suggestion being that animals microinjected with TTX in the left SUB at PND8 present greater reactivity to ketamine than animals microinjected with PBS. These findings could provide new information regarding the involvement of NMDA glutamatergic receptors in the core part of the Nacc in the pathophysiology of schizophrenia.

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An Overview of Animal Models Related to Schizophrenia

Cited by 183 publications

References 179 publications

Epigenomic Dysregulation in Schizophrenia: In Search of Disease Etiology and Biomarkers

Epigenomic Dysregulation in Schizophrenia: In Search of Disease Etiology and Biomarkers

Galphimia glauca and Natural Galphimines Block Schizophrenia-Like Symptoms Induced with Apomorphine and MK-801 in Mice

Postnatal functional inactivation of the ventral subiculum enhances dopaminergic responses in the core part of the nucleus accumbens following ketamine injection in adult rats

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