Our previous neurocognitive studies of schizophrenia outlined two clusters of affected subjects--cognitively spared (CS) and cognitive deficit (CD), the latter's characteristics pointing to developmental origins and impaired synaptic plasticity. Here we investigate the contribution of polymorphisms in major regulators of these processes to susceptibility to schizophrenia and to CD in patients. We examine variation in genes encoding proteins at the gateway of Reelin signaling: ligands RELN and APOE, their common receptors APOER2 and VLDLR, and adaptor DAB1. Association analysis with disease outcome and cognitive performance in the Western Australian Family Study of Schizophrenia (WAFSS) was followed by replication analysis in the Australian Schizophrenia Research Bank (ASRB) and in the Health in Men Study (HIMS) of normal aging males. In the WAFSS sample, we observed significant association of APOE, APOER2, VLDLR, and DAB1 SNPs with disease outcome in the case-control and CD-control datasets, and with pre-morbid intelligence and verbal memory in cases. HIMS replication analysis supported rs439401 (APOE regulatory region), and rs2297660 and rs3737983 (APOER2), with an effect on memory performance in normal aging subjects consistent with the findings in schizophrenia cases. APOER2 gene expression analysis revealed lower transcript levels in lymphoblastoid cells from cognitively impaired schizophrenia patients of the alternatively spliced exon 19, mediating Reelin signaling and synaptic plasticity in the adult brain. ASRB replication analysis produced marginally significant results, possibly reflecting a recruitment strategy biased toward CS patients. The data suggest a contribution of neurodevelopmental/synaptic plasticity genes to cognitive impairment in schizophrenia.

Download full-text PDF

Source
http://dx.doi.org/10.1002/ajmg.b.32042DOI Listing

Publication Analysis

Top Keywords

reelin signaling
12
replication analysis
12
schizophrenia
8
synaptic plasticity
8
schizophrenia patients
8
apoer2 vldlr
8
disease outcome
8
normal aging
8
analysis
5
impact reelin
4

Similar Publications

Upregulation of olfactory receptors and neuronal-associated genes highlights complex immune and neuronal dysregulation in Long COVID patients.

Brain Behav Immun

November 2024

Mike Petryk School of Dentistry, Division of Foundational Sciences, University of Alberta, Edmonton T6G 2E1, AB, Canada; Li Ka Shing Institute of Virology, University of Alberta, Edmonton T6G 2E1, AB, Canada; Women and Children Health Research Institute, University of Alberta, Edmonton T6G 2E1, AB, Canada; Cancer Research Institute of Northern Alberta, University of Alberta, Edmonton T6G 2E1, AB, Canada; Glycomics Institute of Alberta, Faculty of Medicine and Dentistry, University of Alberta, Edmonton T6G 2E1, AB, Canada. Electronic address:

A substantial portion of patients infected with SARS-CoV-2 experience prolonged complications, known as Long COVID (LC). A subset of these patients exhibits the most debilitating symptoms, similar to those defined in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). We performed bulk RNA sequencing (RNAseq) on the whole blood of LC with ME/CFS, at least 12 months post-onset of the acute disease, and compared them with controls.

View Article and Find Full Text PDF

Characterization of GABAergic marker expression in prefrontal cortex in dexamethasone induced depression/anxiety model.

Front Endocrinol (Lausanne)

November 2024

Henan Provincial Engineering Center for Tumor Molecular Medicine, Kaifeng Key Laboratory of Cell Signal Transduction, Henan University, Kaifeng, China.

Article Synopsis
  • GABAergic interneurons are crucial for maintaining a balance between excitation and inhibition in the brain, particularly in the prefrontal cortex (PFC); an overload of glucocorticoids, like dexamethasone (DEX), can disrupt these cells and increase vulnerability to mental health issues such as depression and anxiety.
  • In a study with adult male mice, chronic DEX treatment led to observed behaviors resembling depression and anxiety, as well as reduced levels of important GABAergic markers and a decrease in brain size and cortex thickness.
  • The findings suggest that the decline in GABAergic interneurons due to high DEX exposure may contribute to emotional and behavioral deficits, pointing towards a potential link between glucocorticoid
View Article and Find Full Text PDF

We investigated the effects of epigenetic modifications on post-traumatic stress disorder (PTSD) using a novel combination of herbal medicines from , , , and . The herbal formula extract (HFE) (250 mg/kg) was administered orally once daily for 14 days to determine its effects on PTSD in mice by combining prolonged stress and foot shock. The open field and Y-maze tests determined the effect of HFE on PTSD-induced anxiety and cognition.

View Article and Find Full Text PDF
Article Synopsis
  • * By using immunofluorescence staining, researchers analyzed the protein expressions of different connexins (Cx37, Cx40, Cx43, Cx45) and related proteins (Dab1, Reelin) at two embryonic stages (E13.5 and E15.5).
  • * The findings showed distinct expression patterns among the connexins, suggesting that these proteins might influence retinal development and could be potential targets for treating retinal diseases.
View Article and Find Full Text PDF
Article Synopsis
  • Traumatic brain injury (TBI) can hurt connections in the brain, making it hard for people to move and feel properly. CCL5 is a protein that may help protect the brain and support healing.
  • Scientists tested CCL5 on mice with mild brain injuries to see if it could improve their movement and feeling abilities.
  • The results showed that using CCL5 helped the injured mice's brains recover better, fixing important connections and supporting growth in their brain cells.
View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!