SNAP-25a/b Isoform Levels in Human Brain Dorsolateral Prefrontal Cortex and Anterior Cingulate Cortex

Thompson, Peter M.; Cruz, Dianne A.; Fucich, Elizabeth A.; Olukotun, D. Y.; Takahashi, Masami; Itakura, Makoto

doi:10.1159/000441224

Cited by 4 publications

(1 citation statement)

References 55 publications

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“…In addition to the neuronal functions and pathways associated with Snap25 and Gria2 , both genes have been implicated in several neuropsychiatric disorders. Some studies suggest that Snap25 imbalances, or changes in expression of SNAP25-a and SNAP25-b isoforms, contribute to ADHD and schizophrenia, as well as alcohol use disorder (AUD) and smoking risk [ 68 , 69 , 70 , 71 ]. Gria2 has also been deemed an addiction-related gene, and HuD has been shown to regulate this mRNA and addiction-related behavior [ 67 ].…”

Section: Discussionmentioning

confidence: 99%

The RNA-Binding Protein HuD Regulates Alternative Splicing and Alternative Polyadenylation in the Mouse Neocortex

et al. 2021

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The neuronal Hu/ELAV-like proteins HuB, HuC and HuD are a class of RNA-binding proteins that are crucial for proper development and maintenance of the nervous system. These proteins bind to AU-rich elements (AREs) in the untranslated regions (3′-UTRs) of target mRNAs regulating mRNA stability, transport and translation. In addition to these cytoplasmic functions, Hu proteins have been implicated in alternative splicing and alternative polyadenylation in the nucleus. The purpose of this study was to identify transcriptome-wide effects of HuD deletion on both of these nuclear events using RNA sequencing data obtained from the neocortex of Elavl4–/– (HuD KO) mice. HuD KO affected alternative splicing of 310 genes, including 17 validated HuD targets such as Cbx3, Cspp1, Snap25 and Gria2. In addition, deletion of HuD affected polyadenylation of 53 genes, with the majority of significantly altered mRNAs shifting towards usage of proximal polyadenylation signals (PAS), resulting in shorter 3′-UTRs. None of these genes overlapped with those showing alternative splicing events. Overall, HuD KO had a greater effect on alternative splicing than polyadenylation, with many of the affected genes implicated in several neuronal functions and neuropsychiatric disorders.

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Section: Discussionmentioning

confidence: 99%

The RNA-Binding Protein HuD Regulates Alternative Splicing and Alternative Polyadenylation in the Mouse Neocortex

et al. 2021

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SNAP-25 in Major Psychiatric Disorders: A Review

2019

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Synaptic loss in schizophrenia: a meta-analysis and systematic review of synaptic protein and mRNA measures

et al. 2018

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Although synaptic loss is thought to be core to the pathophysiology of schizophrenia, the nature, consistency and magnitude of synaptic protein and mRNA changes has not been systematically appraised. Our objective was thus to systematically review and meta-analyse findings. The entire PubMed database was searched for studies from inception date to the 1st of July 2017. We selected case-control postmortem studies in schizophrenia quantifying synaptic protein or mRNA levels in brain tissue. The difference in protein and mRNA levels between cases and controls was extracted and meta-analysis conducted. Among the results, we found a significant reduction in synaptophysin in schizophrenia in the hippocampus (effect size: -0.65, p<0.01), frontal (effect size: -0.36, p=0.04), and cingulate cortices (effect size: -0.54, p=0.02), but no significant changes for synaptophysin in occipital and temporal cortices, and no changes for SNAP-25, PSD-95, VAMP and syntaxin in frontal cortex. There were insufficient studies for meta-analysis of complexins, synapsins, rab3A and synaptotagmin and mRNA measures. Findings are summarised for these, which generally show reductions in SNAP-25, PSD-95, synapsin and rab3A protein levels in the hippocampus but inconsistency in other regions. Our findings of moderate-large reductions in synaptophysin in hippocampus and frontal cortical regions, and a tendency for reductions in other pre- and post-synaptic proteins in the hippocampus are consistent with models that implicate synaptic loss in schizophrenia. However, they also identify potential differences between regions and proteins, suggesting synaptic loss is not uniform in nature or extent.

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SNAP-25a/b Isoform Levels in Human Brain Dorsolateral Prefrontal Cortex and Anterior Cingulate Cortex

Cited by 4 publications

References 55 publications

The RNA-Binding Protein HuD Regulates Alternative Splicing and Alternative Polyadenylation in the Mouse Neocortex

The RNA-Binding Protein HuD Regulates Alternative Splicing and Alternative Polyadenylation in the Mouse Neocortex

SNAP-25 in Major Psychiatric Disorders: A Review

Synaptic loss in schizophrenia: a meta-analysis and systematic review of synaptic protein and mRNA measures

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