The effects of antipsychotics on behavioral abnormalities of the Gunn rat (unconjugated hyperbilirubinemia rat), a rat model of schizophrenia

Tsuchie, Keiko; Miyaoka, Tsuyoshi; Furuya, Motohide; Liaury, Kristian; Ieda, Masa; Wake, Rei; Horiguchi, Jun; Takechi, Mayumi

doi:10.1016/j.ajp.2012.09.007

Cited by 19 publications

(13 citation statements)

References 27 publications

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“…Moreover, numerous studies have confirmed the PPI deficiency in schizophrenic patients [46–48] and that antipsychotic drugs can not only ameliorate symptoms of schizophrenia but also improve the PPI deficit [49, 50]. Our previous studies have demonstrated that Gunn rats exhibit a schizophrenia-like behavior which consists of impaired sensorimotor gating as shown by decreased %PPI compared to Wistar rats, a normal rat strain [25, 26, 28]. Accordingly, Gunn rats showing such a schizophrenia-like behavior seems to be an appropriate animal model to investigate the therapeutic mechanism of ECS, the animal counterpart of ECT.…”

Section: Discussionmentioning

confidence: 99%

“…This deficiency leads to high levels of unconjugated bilirubin in their blood and various tissue, including the brain [23, 24]. Our previous studies have revealed that Gunn rats show a behavioral abnormality similar to schizophrenia with deficits in prepulse inhibition (PPI) [25, 26]. Furthermore, we have shown that microglia are activated in the hippocampal dentate gyrus (DG) of Gunn rats [27, 28].…”

Section: Introductionmentioning

confidence: 99%

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Electroconvulsive shock attenuated microgliosis and astrogliosis in the hippocampus and ameliorated schizophrenia-like behavior of Gunn rat

Limoa

Hashioka

Miyaoka

et al. 2016

J Neuroinflammation

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BackgroundAlthough electroconvulsive therapy (ECT) is regarded as one of the efficient treatments for intractable psychiatric disorders, the mechanism of therapeutic action remains unclear. Recently, many studies indicate that ECT affects the immune-related cells, such as microglia, astrocytes, and lymphocytes. Moreover, microglial activation and astrocytic activation have been implicated in the postmortem brains of schizophrenia patients. We previously demonstrated that Gunn rats showed schizophrenia-like behavior and microglial activation in their brains. The present study examined the effects of electroconvulsive shock (ECS), an animal counterpart of ECT, on schizophrenia-like behavior, microgliosis, and astrogliosis in the brain of Gunn rats.MethodsThe rats were divided into four groups, i.e., Wistar sham, Wistar ECS, Gunn sham, and Gunn ECS. ECS groups received ECS once daily for six consecutive days. Subsequently, prepulse inhibition (PPI) test was performed, and immunohistochemistry analysis was carried out to determine the activation degree of microglia and astrocytes in the hippocampus by using anti-CD11b and anti-glial fibrillary acidic protein (GFAP) antibody, respectively.ResultsWe found PPI deficit in Gunn rats compared to Wistar rats, and it was significantly improved by ECS. Immunohistochemistry analysis revealed that immunoreactivity of CD11b and GFAP was significantly increased in Gunn rats compared to Wistar rats. ECS significantly attenuated the immunoreactivity of both CD11b and GFAP in Gunn rats.ConclusionsECS ameliorated schizophrenia-like behavior of Gunn rats and attenuated microgliosis and astrogliosis in the hippocampus of Gunn rats. Accordingly, therapeutic effects of ECT may be exerted, at least in part, by inhibition of glial activation. These results may provide crucial information to elucidate the role of activated glia in the pathogenesis of schizophrenia and to determine whether future therapeutic interventions should attempt to up-regulate or down-regulate glial functions.Electronic supplementary materialThe online version of this article (doi:10.1186/s12974-016-0688-2) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Electroconvulsive shock attenuated microgliosis and astrogliosis in the hippocampus and ameliorated schizophrenia-like behavior of Gunn rat

Limoa

Hashioka

Miyaoka

et al. 2016

J Neuroinflammation

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“…This is also right for Gunn rat, another substrain with schizophrenia like symptoms (Tsuchie et al, 2013). Furthermore, our preliminary studies showed that the food restriction for two days should be enough for animals to evoke hunger, and the low amount of food rewards cannot lead to satiation in either group.…”

Section: Methodological Aspectsmentioning

confidence: 98%

Characterization of exploratory activity and learning ability of healthy and “schizophrenia-like” rats in a square corridor system (AMBITUS)

Horváth

Liszli

Kekesi

et al. 2017

Physiology & Behavior

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The rodent tasks with food rewards are useful methods to evaluate memory functions, including hole-board and corridor tests. The AMBITUS system (a square corridor with several food rewards), as a combination of these tests, was developed for the investigation of a variety of parameters associated with exploration and cognitive performance in rodents. Experiments were performed to characterize these behaviors in healthy rats and a new "schizophrenia-like" rat substrain with impaired learning ability to reveal the reliability in tests related to these functions.A square corridor was constructed with equally spaced sites along each wall (4 inside and 4 outside) resulting in 16 side-boxes for food rewards. Photocells at each box recorded the visits into the side-boxes (as exploratory activity), while the eating parameters were obtained from video records. The animals were exposed to two types of tasks repeatedly in two series: all (16) or only the inside (8) boxes (Task 1 or Task 2, respectively) were baited.Most of the rats acquired Task 1, and their performance improved by repetition, but the new substrain showed decreased exploration and learning capacity. The introduction of Task 2 caused prompt preference of the baited inner side-boxes, and gradually improved working and reference memory during the trials. The manual and automated scoring of the visits into the side-boxes showed significant (r=0.97) correlation.The results proved that healthy animals could perform the simple tasks in the square corridor after a few repetitions. The semi-automated AMBITUS system might be appropriate to detect cognitive flexibility after different manipulations, and it provides immediate, online assessment of exploratory behavior of a large number of animals within a short period of time, and it reduces the possibility of experimenter bias.

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“…Emerging evidence supports a subtle-kernicteric syndrome that is referred to as bilirubin-induced neurological dysfunction (BIND). BIND has been linked to a range of neuropsychiatric syndromes that persist into adulthood, including attention deficit-hyperactivity disorder, autism, and schizophrenia ( 3 – 6 ). Even with modest co-morbidities, the incidence of neonatal jaundice justifies further exploration of links between these disorders and BIND.…”

Section: Introductionmentioning

confidence: 99%

Hyperactivity in the Gunn rat model of neonatal jaundice: age-related attenuation and emergence of gait deficits

et al. 2014

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BackgroundNeonatal jaundice resulting from elevated unconjugated bilirubin (UCB) occurs in 60–80% of newborn infants. Although mild jaundice is generally considered harmless, little is known about its long-term consequences. Recent studies have linked mild bilirubin-induced neurological dysfunction (BIND) with a range of neurological syndromes, including attention deficit-hyperactivity disorder. The goal of this study was to measure BIND across the lifespan in the Gunn rat model of BIND.MethodsUsing a sensitive force plate actometer, we measured locomotor activity and gait in jaundiced (jj) Gunn rats versus their non-jaundiced (Nj) littermates. Data were analyzed for young adult (3–4 months), early middle-aged (9–10 months), and late middle-aged (17–20 months) male rats.Resultsjj rats exhibited lower body weights at all ages and a hyperactivity that resolved at 17–20 months of age. Increased propulsive force and gait velocity accompanied hyperactivity during locomotor bouts at 9–10 months in jj rats. Stride length did not differ between the two groups at this age. Hyperactivity normalized and gait deficits, including decreased stride length, propulsive force, and gait velocity, emerged in the 17–20-month-old jj rats.ConclusionsThese results demonstrate that, in aging, hyperactivity decreases with the onset of gait deficits in the Gunn rat model of BIND.

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The effects of antipsychotics on behavioral abnormalities of the Gunn rat (unconjugated hyperbilirubinemia rat), a rat model of schizophrenia

Cited by 19 publications

References 27 publications

Electroconvulsive shock attenuated microgliosis and astrogliosis in the hippocampus and ameliorated schizophrenia-like behavior of Gunn rat

Electroconvulsive shock attenuated microgliosis and astrogliosis in the hippocampus and ameliorated schizophrenia-like behavior of Gunn rat

Characterization of exploratory activity and learning ability of healthy and “schizophrenia-like” rats in a square corridor system (AMBITUS)

Hyperactivity in the Gunn rat model of neonatal jaundice: age-related attenuation and emergence of gait deficits

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