Dataset Information

NPTX2 is a key component in the regulation of anxiety.

ABSTRACT: Anxiety disorders significantly impair quality of life. However, limited knowledge of the underlying mechanisms impedes the development of effective therapeutics. Previous studies have suggested that the expression of the Nptx2 gene is associated with anxiety, but the neurobiological processes underlying this association remain unclear. We generated multiple mouse models with knockout or overexpression of Nptx2 in specific brain regions and during different developmental stages to assess anxiety, adult neurogenesis, and glucocorticoid-related gene expression. Our results provide evidence that Nptx2 expression in the adult hippocampus regulates anxiety in mice. Eliminating Nptx2 expression in either the developing mouse brain or in adulthood leads to increased anxiety levels. The increase in anxiety was evident in hippocampus-specific Nptx2 knockout mice, but not in an amygdala specific knockouts. Gene expression analysis revealed increased expression of glucocorticoid receptor target genes in Nptx2 knockout mice after acute stress. Overexpression of Nptx2 in the hippocampus alleviates stress-induced anxious behaviors and reverses the changes in expression of glucocorticoid receptor related genes. In conclusion, we demonstrate that Nptx2 in the hippocampus performs a critical role in modulating anxiety, hippocampal cell proliferation, and glucocorticoid receptor related gene expression. Our results suggest Nptx2 may be a potential target for anxiolytic therapeutics.

SUBMITTER: Chang S

PROVIDER: S-EPMC6046040 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

NPTX2 is a key component in the regulation of anxiety.

Chang Simon S Bok Philane P Tsai Ching-Yen CY Sun Cheng-Pu CP Liu Hsuan H Deussing Jan M JM Huang Guo-Jen GJ

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 20180511 9

Anxiety disorders significantly impair quality of life. However, limited knowledge of the underlying mechanisms impedes the development of effective therapeutics. Previous studies have suggested that the expression of the Nptx2 gene is associated with anxiety, but the neurobiological processes underlying this association remain unclear. We generated multiple mouse models with knockout or overexpression of Nptx2 in specific brain regions and during different developmental stages to assess anxiety ...[more]

PMID: 29844474

Similar Datasets

Project description:The Ufm1 conjugation system is an ubiquitin-like modification system that consists of Ufm1, Uba5 (E1), Ufc1 (E2), and less defined E3 ligase(s) and targets. The biological importance of this system is highlighted by its essential role in embryogenesis and erythroid development, but the underlying mechanism is poorly understood. UFBP1 (Ufm1 binding protein 1, also known as DDRGK1, Dashurin and C20orf116) is a putative Ufm1 target, yet its exact physiological function and impact of its ufmylation remain largely undefined. In this study, we report that UFBP1 is indispensable for embryonic development and hematopoiesis. While germ-line deletion of UFBP1 caused defective erythroid development and embryonic lethality, somatic ablation of UFBP1 impaired adult hematopoiesis, resulting in pancytopenia and animal death. At the cellular level, UFBP1 deficiency led to elevated ER (endoplasmic reticulum) stress and activation of unfolded protein response (UPR), and consequently cell death of hematopoietic stem/progenitor cells. In addition, loss of UFBP1 suppressed expression of erythroid transcription factors GATA-1 and KLF1 and blocked erythroid differentiation from CFU-Es (colony forming unit-erythroid) to proerythroblasts. Interestingly, depletion of Uba5, a Ufm1 E1 enzyme, also caused elevation of ER stress and under-expression of erythroid transcription factors in erythroleukemia K562 cells. By contrast, knockdown of ASC1, a newly identified Ufm1 target that functions as a transcriptional co-activator of hormone receptors, led to down-regulation of erythroid transcription factors, but did not elevate basal ER stress. Furthermore, we found that ASC1 was associated with the promoters of GATA-1 and Klf1 in a UFBP1-dependent manner. Taken together, our findings suggest that UFBP1, along with ASC1 and other ufmylation components, play pleiotropic roles in regulation of hematopoietic cell survival and differentiation via modulating ER homeostasis and erythroid lineage-specific gene expression. Modulating the activity of this novel ubiquitin-like system may represent a novel approach to treat blood-related diseases such as anemia.

Dataset Information

NPTX2 is a key component in the regulation of anxiety.

Publications

NPTX2 is a key component in the regulation of anxiety.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure