Mouse behavioral endophenotypes for schizophrenia

Amann, L; Gandal, Michael J.; Halene, Tobias B.; Ehrlichman, Richard S.; White, Samantha; McCarren, Hilary S.; Siegel, Steven J.

doi:10.1016/j.brainresbull.2010.04.008

Cited by 152 publications

(128 citation statements)

References 160 publications

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“…1993), gene knockout models (Papaleo et al, 2012), pharmacological models (Amann et al, 2010), neurodevelopmental models (Wilson and Terry, 2010) and additional stress models (Oliver, 2011). Given the large numbers of rodent models currently used to mimic the phenotypes associated with SZ, it is becoming increasingly clear that validating these models will depend on the extent to which clinicians provide pertinent behavioral information and the accuracy with which behavioral testing of mice mimics the human endophenotype (Young et al, 2010).…”

Section: Prenatal Restraint Stress Model Of Psychosismentioning

confidence: 99%

The Dynamics of DNA Methylation in Schizophrenia and Related Psychiatric Disorders

Grayson

Guidotti

2012

Neuropsychopharmacol

242

214

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Major psychiatric disorders such as schizophrenia (SZ) and bipolar disorder (BP) with psychosis (BP+ ) express a complex symptomatology characterized by positive symptoms, negative symptoms, and cognitive impairment. Postmortem studies of human SZ and BP+ brains show considerable alterations in the transcriptome of a variety of cortical structures, including multiple mRNAs that are downregulated in both inhibitory GABAergic and excitatory pyramidal neurons compared with non-psychiatric subjects (NPS). Several reports show increased expression of DNA methyltransferases in telencephalic GABAergic neurons. Accumulating evidence suggests a critical role for altered DNA methylation processes in the pathogenesis of SZ and related psychiatric disorders. The establishment and maintenance of CpG site methylation is essential during central nervous system differentiation and this methylation has been implicated in synaptic plasticity, learning, and memory. Atypical hypermethylation of candidate gene promoters expressed in GABAergic neurons is associated with transcriptional downregulation of the corresponding mRNAs, including glutamic acid decarboxylase 67 (GAD67) and reelin (RELN). Recent reports indicate that the methylation status of promoter proximal CpG dinucleotides is in a dynamic balance between DNA methylation and DNA hydroxymethylation. Hydroxymethylation and subsequent DNA demethylation is more complex and involves additional proteins downstream of 5-hydroxymethylcytosine, including members of the base excision repair (BER) pathway. Recent advances in our understanding of altered CpG methylation, hydroxymethylation, and active DNA demethylation provide a framework for the identification of new targets, which may be exploited for the pharmacological intervention of the psychosis associated with SZ and possibly BP+ .

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Section: Prenatal Restraint Stress Model Of Psychosismentioning

confidence: 99%

The Dynamics of DNA Methylation in Schizophrenia and Related Psychiatric Disorders

Grayson

Guidotti

2012

Neuropsychopharmacol

242

214

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“…3H ), which all depend on proper function of the hippocampus. We used additional mice to investigate PPI of the startle response, a specific form of sensory motor gating that is impaired in mouse models for schizophrenia (SZ) and in SZ patients (Amann et al, 2010). Interestingly, PPI measured at moderate prepulse intensities was significantly increased in AAV-HDAC1-GFP-injected mice compared with the AAV-GFP group (Fig.…”

Section: Cognitive Function In Aav-hdac1-gfp-injected Micementioning

confidence: 99%

HDAC1 Regulates Fear Extinction in Mice

Bahari‐Javan

Maddalena²,

Kerimoğlu³

et al. 2012

J. Neurosci.

168

140

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Histone acetylation has been implicated with the pathogenesis of neuropsychiatric disorders and targeting histone deacetylases (HDACs) using HDAC inhibitors was shown to be neuroprotective and to initiate neuroregenerative processes. However, little is known about the role of individual HDAC proteins during the pathogenesis of brain diseases. HDAC1 was found to be upregulated in patients suffering from neuropsychiatric diseases. Here, we show that virus-mediated overexpression of neuronal HDAC1 in the adult mouse hippocampus specifically affects the extinction of contextual fear memories, while other cognitive abilities were unaffected. In subsequent experiments we show that under physiological conditions, hippocampal HDAC1 is required for extinction learning via a mechanism that involves H3K9 deacetylation and subsequent trimethylation of target genes. In conclusion, our data show that hippocampal HDAC1 has a specific role in memory function.

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“…Therefore, current animal models of schizophrenia are intended to assess specific endophenotypes instead of modeling the disease as a whole (Amann et al 2010;Kaffman and Krystal 2012;Robbins 2012).The identification of rodent endophenotypes represents a critical step to elucidate the neurobiological basis of the deficits and the development of new treatment strategies.…”

Section: Introductionmentioning

confidence: 99%