| 1 | Biol. Psychiatry 2015 Dec 78: 848-59 |
|---|---|
| PMID | 25792222 |
| Title | Long Noncoding RNA-Directed Epigenetic Regulation of Gene Expression Is Associated With Anxiety-like Behavior in Mice. |
| Abstract | RNA-directed regulation of epigenetic processes has recently emerged as an important feature of mammalian differentiation and development. Perturbation of this regulatory system in the brain may contribute to the development of neuropsychiatric disorders. RNA sequencing was used to identify changes in the experience-dependent expression of long noncoding RNAs (lncRNAs) within the medial prefrontal cortex of adult mice. Transcripts were validated by real-time quantitative polymerase chain reaction and a candidate lncRNA, Gomafu, was selected for further investigation. The functional role of this schizophrenia-related lncRNA was explored in vivo by antisense oligonucleotide-mediated gene knockdown in the medial prefrontal cortex, followed by behavioral training and assessment of fear-related anxiety. Long noncoding RNA-directed epigenetic regulation of gene expression was investigated by chromatin and RNA immunoprecipitation assays. RNA sequencing analysis revealed changes in the expression of a significant number of genes related to neural plasticity and stress, as well as the dynamic regulation of lncRNAs. In particular, we detected a significant downregulation of Gomafu lncRNA. Our results revealed that Gomafu plays a role in mediating anxiety-like behavior and suggest that this may occur through an interaction with a key member of the polycomb repressive complex 1, BMI1, which regulates the expression of the schizophrenia-related gene beta crystallin (CRYBB1). We also demonstrated a novel role for CRYBB1 in mediating fear-induced anxiety-like behavior. Experience-dependent expression of lncRNAs plays an important role in the epigenetic regulation of adaptive behavior, and the perturbation of Gomafu may be related to anxiety and the development of neuropsychiatric disorders. |
| SCZ Keywords | schizophrenia |
| 2 | Exp. Eye Res. 2015 Nov -1: -1 |
| PMID | 26593886 |
| Title | From eyeless to neurological diseases. |
| Abstract | Age-related cataracts are frequently associated with degenerative changes in the ocular lens including the aggregation of proteins - mainly crystallins, but also other proteins including amyloids (A?) leading to the hypothesis that cataracts could be used as "biomarkers" for Alzheimer disease. Even if this hypothesis was rejected by David Beebe's last paper (Bei et al., Exp. Eye Res., in press), it is a fascinating aspect to look for commonalities between eye diseases and neurological disorders. In this review, I discuss such commonalities between eye and brain mainly from a developmental point of view. The finding of the functional homology of the Drosophila eyeless gene with the mammalian Pax6 gene marks a first highlight in the developmental genetics of the eye - this result destroyed the "dogma" of the different evolutionary routes of eye development in flies and mammals. The second highlight was the finding that Pax6 is also involved in the development of the forebrain supporting the pleiotropic role of many genes. These findings opened a new avenue for research showing that a broad variety of transcription factors, but also structural proteins are involved both, in eye and brain development as well as into the maintenance of the functional integrity of the corresponding tissue(s). In this review recent findings are summarized demonstrating that genes whose mutations have been identified first to be causative for congenital or juvenile eye disorders are also involved in regenerative processes and neurogenesis (Pax6), but also in neurodegenerative diseases like Parkinson (e.g. Pitx3) or in neurological disorders like schizophrenia (e.g. CRYBB1, Crybb2). |
| SCZ Keywords | schizophrenia |