Hippocampal novelty activations in schizophrenia: Disease and medication effects

Tamminga, Carol A.; Thomas, Binu P.; Chin, R; Mihalakos, Perry; Youens, Kenneth; Wagner, Anthony D.; Preston, Alison R.

doi:10.1016/j.schres.2012.03.019

Cited by 30 publications

(22 citation statements)

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“…Furthermore, increasing evidence implies that the hippocampus is involved in the pathophysiology of schizophrenia [61–63] and is particularly vulnerable to inflammatory insults due to its high density of receptors for inflammatory mediators [64, 65]. …”

Section: Discussionmentioning

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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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%

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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“…Structural MRI studies have demonstrated reductions in MTL volume [4, 43–46], while fMRI studies have revealed altered MTL activity at rest [47–51], and altered MTL activation during cognitive tasks involving the processing of salient information in the domains of emotion [52–54], novelty [55], and reward processing [56]. Schizophrenia has also been associated with increased hippocampal glutamate levels [57, 58], although increased glutamate levels have also been identified in several regions other than the MTL [57, 59–61].…”

Section: Are Data From Studies In Schizophrenia Consistent With the Mmentioning

confidence: 99%

Translating the MAM model of psychosis to humans

Modinos

Allen

Grace

et al. 2015

Trends in Neurosciences

148

122

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Elevated dopamine function and alterations in the medial temporal lobe structure and function (MTL) are two of the most robust findings in schizophrenia, but how interactions between these abnormalities underlie the onset of psychosis is unclear. Although several preclinical models of psychosis have been proposed, the methylazoxymethanol acetate (MAM) rodent model provides a mechanistic account linking these two clinical observations. The model proposes that psychosis develops as a result of a perturbation of MTL function, leading to elevated striatal dopamine dysfunction. We review a number of recent neuroimaging studies that examine components of the putative model in people with an ultra high risk (UHR) of psychosis. Whilst data from these studies are broadly consistent with the MAM model, that the potential for comparing various kinds of neurobiological data across animal and human studies imposes some limitations on what can be inferred from these data. Going forward, longitudinal studies are needed to explicitly test the model’s predictions in UHR populations.

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“…Despite these molecular insights, the contribution of iDG to the cognitive impairments observed in these neuropsychiatric disorders remains unclear. One hypothesis is that the increased proportion of immature neurons in the DG causes deficits in pattern separation and hyper-activity in CA3-CA1, thereby conferring the psychosis observed in the patients (Tamminga et al, 2012). However, much additional work is needed to better understand the pathogenesis and functional consequences of iDG.…”

Section: Box 1 Immature Dentate Gyrus In Neuropsychiatric Diseasesmentioning

confidence: 99%

How to make a hippocampal dentate gyrus granule neuron

Marchetto

Gage

2014

Development

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Granule neurons in the hippocampal dentate gyrus (DG) receive their primary inputs from the cortex and are known to be continuously generated throughout adult life. Ongoing integration of newborn neurons into the existing hippocampal neural circuitry provides enhanced neuroplasticity, which plays a crucial role in learning and memory; deficits in this process have been associated with cognitive decline under neuropathological conditions. In this Primer, we summarize the developmental principles that regulate the process of DG neurogenesis and discuss recent advances in harnessing these developmental cues to generate DG granule neurons from human pluripotent stem cells.

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Hippocampal novelty activations in schizophrenia: Disease and medication effects

Cited by 30 publications

References 50 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

Translating the MAM model of psychosis to humans

How to make a hippocampal dentate gyrus granule neuron

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