Associations of NEUROD2 polymorphisms and change of cognitive dysfunctions in schizophrenia and schizoaffective disorder after eight weeks of antipsychotic treatment

Spellmann, Ilja; Riedel, Michael; Städtler, Julia; Zill, Peter; Obermeier, Michael; Cerovecki, Anja; Dehning, Sandra; Schennach, Rebecca; Epple, Maria; Opgen-Rhein, M.; Müller, Norbert; Bondy, Brigitta; Möller, Hans‐Jürgen; Musil, Richard

doi:10.1080/13546805.2017.1322502

Cited by 16 publications

(8 citation statements)

References 53 publications

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“…We identified PTSD-associated CpGs in genes implicated in other neuropsychiatric disorders (e.g. AGBL1, ATP9A, FLJ46321, GOT2, HOXA3, MAP7, and NEUROD2) [40][41][42][43][44][45] , which may provide insight into comorbidities commonly reported in PTSD. We also identified CpGs in genes that are involved in other epigenetic mechanisms (e.g.…”

Section: Discussionmentioning

confidence: 99%

Epigenome-wide meta-analysis of PTSD across 10 military and civilian cohorts identifies novel methylation loci

Ratanatharathorn

et al. 2019

Preprint

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Differences in susceptibility to posttraumatic stress disorder (PTSD) may be related to epigenetic differences between PTSD cases and trauma-exposed controls. Such epigenetic differences may provide insight into the biological processes underlying the disorder. Here we describe the results of the largest DNA methylation meta-analysis of PTSD to date with data from the Psychiatric Genomics Consortium (PGC) PTSD Epigenetics Workgroup. Ten cohorts, military and civilian, contributed blood-derived DNA methylation data (HumanMethylation450 BeadChip) from 1,896 PTSD cases (42%) and trauma-exposed controls (58%). Utilizing a common QC and analysis strategy, we identified ten CpG sites associated with PTSD (9.61E-07

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Section: Discussionmentioning

confidence: 99%

Epigenome-wide meta-analysis of PTSD across 10 military and civilian cohorts identifies novel methylation loci

Ratanatharathorn

et al. 2019

Preprint

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“…The authors of this study also suggest that behavioral deficits in social behavior, which are reminiscent of autistic disorders, can be found in Neurod2 mutant mice. In addition, Spellman et al identified a direct association of NEUROD2 gene polymorphisms with changes in cognitive functions present in schizophrenic patients treated with antipsychotic drugs (Spellmann et al, 2017 ). It has also been shown that the lateral and basolateral amygdala nuclei fail to form in Neurod2 mutant mice, and that these mice display deficits in emotional learning (Lin et al, 2005 ).…”

Section: Neurod Genes In Human Neurological Disordersmentioning

confidence: 99%

The Role of Neurod Genes in Brain Development, Function, and Disease

Tutukova

Tarabykin

Hernández-Miranda

2021

Front. Mol. Neurosci.

101

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Transcriptional regulation is essential for the correct functioning of cells during development and in postnatal life. The basic Helix-loop-Helix (bHLH) superfamily of transcription factors is well conserved throughout evolution and plays critical roles in tissue development and tissue maintenance. A subgroup of this family, called neural lineage bHLH factors, is critical in the development and function of the central nervous system. In this review, we will focus on the function of one subgroup of neural lineage bHLH factors, the Neurod family. The Neurod family has four members: Neurod1, Neurod2, Neurod4, and Neurod6. Available evidence shows that these four factors are key during the development of the cerebral cortex but also in other regions of the central nervous system, such as the cerebellum, the brainstem, and the spinal cord. We will also discuss recent reports that link the dysfunction of these transcription factors to neurological disorders in humans.

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“…Neurod2 knockout animals exhibit morphological and physiological defects in various brain regions, including thalamocortical connections, hippocampal synaptogenesis, axonal guidance of callosal axons, development of amygdalar nuclei, cortical fasciculation, targeted axogenesis of compact fiber tracts as well as differences in intrinsic excitability during cortical development (Olson et al, 2001;Lin et al, 2005;Ince-Dunn et al, 2006;Wilke et al, 2012;Bormuth et al, 2013;Chen et al, 2016). Accordingly, disruption of NeuroD2 function has been implicated in several neurodevelopmental, neuropsychiatric and mood disorders, such as autism (Runge et al, 2020), depression (Bagot et al, 2016), schizophrenia (Spellmann et al, 2017), or epilepsy (Sega et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

PKN1 Is a Novel Regulator of Hippocampal GluA1 Levels

Safari

Obexer

Baier‐Bitterlich

et al. 2021

Front. Synaptic Neurosci.

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Alterations in the processes that control α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) expression, assembly and trafficking are closely linked to psychiatric and neurodegenerative disorders. We have recently shown that the serine/threonine kinase Protein kinase N1 (PKN1) is a developmentally active regulator of cerebellar synaptic maturation by inhibiting AKT and the neurogenic transcription factor neurogenic differentiation factor-2 (NeuroD2). NeuroD2 is involved in glutamatergic synaptic maturation by regulating expression levels of various synaptic proteins. Here we aimed to study the effect of Pkn1 knockout on AKT phosphorylation and NeuroD2 levels in the hippocampus and the subsequent expression levels of the NeuroD2 targets and AMPAR subunits: glutamate receptor 1 (GluA1) and GluA2/3. We show that PKN1 is expressed throughout the hippocampus. Interestingly, not only postnatal but also adult hippocampal phospho-AKT and NeuroD2 levels were significantly elevated upon Pkn1 knockout. Postnatal and adult Pkn1–/– hippocampi showed enhanced expression of the AMPAR subunit GluA1, particularly in area CA1. Surprisingly, GluA2/3 levels were not different between both genotypes. In addition to higher protein levels, we also found an enhanced GluA1 content in the membrane fraction of postnatal and adult Pkn1–/– animals, while GluA2/3 levels remained unchanged. This points toward a very specific regulation of GluA1 expression and/or trafficking by the novel PKN1-AKT-NeuroD2 axis. Considering the important role of GluA1 in hippocampal development as well as the pathophysiology of several disorders, ranging from Alzheimer’s, to depression and schizophrenia, our results validate PKN1 for future studies into neurological disorders related to altered AMPAR subunit expression in the hippocampus.

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Associations of NEUROD2 polymorphisms and change of cognitive dysfunctions in schizophrenia and schizoaffective disorder after eight weeks of antipsychotic treatment

Abstract: Our findings suggest that the NEUROD2 gene could play a role in the pathophysiology of neurocognitive dysfunctions as well as in the change of cognitive symptoms under antipsychotic treatment in schizophrenia and schizoaffective disorder.

Cited by 16 publications

References 53 publications

Epigenome-wide meta-analysis of PTSD across 10 military and civilian cohorts identifies novel methylation loci

Epigenome-wide meta-analysis of PTSD across 10 military and civilian cohorts identifies novel methylation loci

The Role of Neurod Genes in Brain Development, Function, and Disease

PKN1 Is a Novel Regulator of Hippocampal GluA1 Levels

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