Matches in SemOpenAlex for { <https://semopenalex.org/work/W1605392775> ?p ?o ?g. }
Showing items 1 to 75 of
75
with 100 items per page.
- W1605392775 abstract "Hypoxic insult during early pregnancy can give rise to neuronal disorders of the newborn, such as autism, schizophrenia and epilepsy. Of these disorders, the underlying similarity is cortical dysplasia, in which the neuronal layers are disrupted due to abnormal neuronal migration. The infliction of hypoxia during the critical period of neuronal development and migration can cause abnormalities which can propagate into these migration defects observed after birth. The purpose of this dissertation is to investigate the effect of hypoxia on early neuronal development, and the role of lysophosphatidic acid receptor-1 (LPA₁) in this pathological process. LPA₁ is one of 6 G-protein-coupled- receptors (GPCRs) which are activated by a bioactive lipid, LPA. It is highly enriched in the ventricular zone of the cortex during development, suggesting its importance in neural progenitor cells (NPCs). Previously, LPA treatment of ex vivo cortices at embryonic age 13.5, a period of neurogenesis and early neuronal migration, was reported to induce ectopic displacement of mitotic NPCs. Strikingly, in this study, a similar displacement of mitotic NPCs, together with delayed early post-mitotic neuronal migration and N-cadherin disruption, was observed in cortices exposed to hypoxia, which was obliterated in LPA₁ null cortices. This indicates that LPA₁ is an essential mediator of hypoxia in the developing cortex. Through the use of pharmacological inhibitors, it was demonstrated that hypoxia signals through LPA₁ through Gi and subsequent downstream effectors. Importantly, a novel mechanism of how hypoxia activates LPA₁ was discovered: Hypoxia inhibits GRK2, a GPCR kinase which associates with LPA₁ to cause sequestration, hence promoting LPA₁ activity. LPA signaling has been implicated in various stages of vascular development, but blood vessel integrity in these receptor knockout mice have not been investigated in depth. In a separate study, it was observed that LPA₁/ LPA₂ double null mice exhibit an increased blood vessel leakage and blood vessel density specifically in the cortex during the period around birth persisting into early postnatal life. Also, these cortical endothelial cells appear to be unhealthy and electron-light. These striking phenotypes could shed light on the role of LPA signaling in blood brain barrier formation in the brain" @default.
- W1605392775 created "2016-06-24" @default.
- W1605392775 creator A5088310997 @default.
- W1605392775 date "2011-01-01" @default.
- W1605392775 modified "2023-09-27" @default.
- W1605392775 title "Lysophosphatidic acid receptor-1 and 2 (LPA1, LPA 2): Novel roles in brain and vascular development" @default.
- W1605392775 hasPublicationYear "2011" @default.
- W1605392775 type Work @default.
- W1605392775 sameAs 1605392775 @default.
- W1605392775 citedByCount "0" @default.
- W1605392775 crossrefType "journal-article" @default.
- W1605392775 hasAuthorship W1605392775A5088310997 @default.
- W1605392775 hasConcept C134018914 @default.
- W1605392775 hasConcept C136834591 @default.
- W1605392775 hasConcept C137738243 @default.
- W1605392775 hasConcept C1491633281 @default.
- W1605392775 hasConcept C169760540 @default.
- W1605392775 hasConcept C170493617 @default.
- W1605392775 hasConcept C178790620 @default.
- W1605392775 hasConcept C185592680 @default.
- W1605392775 hasConcept C201750760 @default.
- W1605392775 hasConcept C2776661833 @default.
- W1605392775 hasConcept C28328180 @default.
- W1605392775 hasConcept C39961270 @default.
- W1605392775 hasConcept C4746552 @default.
- W1605392775 hasConcept C540031477 @default.
- W1605392775 hasConcept C55493867 @default.
- W1605392775 hasConcept C7836513 @default.
- W1605392775 hasConcept C86803240 @default.
- W1605392775 hasConcept C95444343 @default.
- W1605392775 hasConceptScore W1605392775C134018914 @default.
- W1605392775 hasConceptScore W1605392775C136834591 @default.
- W1605392775 hasConceptScore W1605392775C137738243 @default.
- W1605392775 hasConceptScore W1605392775C1491633281 @default.
- W1605392775 hasConceptScore W1605392775C169760540 @default.
- W1605392775 hasConceptScore W1605392775C170493617 @default.
- W1605392775 hasConceptScore W1605392775C178790620 @default.
- W1605392775 hasConceptScore W1605392775C185592680 @default.
- W1605392775 hasConceptScore W1605392775C201750760 @default.
- W1605392775 hasConceptScore W1605392775C2776661833 @default.
- W1605392775 hasConceptScore W1605392775C28328180 @default.
- W1605392775 hasConceptScore W1605392775C39961270 @default.
- W1605392775 hasConceptScore W1605392775C4746552 @default.
- W1605392775 hasConceptScore W1605392775C540031477 @default.
- W1605392775 hasConceptScore W1605392775C55493867 @default.
- W1605392775 hasConceptScore W1605392775C7836513 @default.
- W1605392775 hasConceptScore W1605392775C86803240 @default.
- W1605392775 hasConceptScore W1605392775C95444343 @default.
- W1605392775 hasLocation W16053927751 @default.
- W1605392775 hasOpenAccess W1605392775 @default.
- W1605392775 hasPrimaryLocation W16053927751 @default.
- W1605392775 hasRelatedWork W1793264895 @default.
- W1605392775 hasRelatedWork W1807507622 @default.
- W1605392775 hasRelatedWork W2009121314 @default.
- W1605392775 hasRelatedWork W2009898157 @default.
- W1605392775 hasRelatedWork W2016957999 @default.
- W1605392775 hasRelatedWork W2025059314 @default.
- W1605392775 hasRelatedWork W2032933011 @default.
- W1605392775 hasRelatedWork W2069866488 @default.
- W1605392775 hasRelatedWork W2070729834 @default.
- W1605392775 hasRelatedWork W2093575650 @default.
- W1605392775 hasRelatedWork W2093645209 @default.
- W1605392775 hasRelatedWork W2099489663 @default.
- W1605392775 hasRelatedWork W2110691073 @default.
- W1605392775 hasRelatedWork W2126224335 @default.
- W1605392775 hasRelatedWork W2132733489 @default.
- W1605392775 hasRelatedWork W2154152289 @default.
- W1605392775 hasRelatedWork W2507593969 @default.
- W1605392775 hasRelatedWork W3013847590 @default.
- W1605392775 hasRelatedWork W3196723085 @default.
- W1605392775 hasRelatedWork W343570931 @default.
- W1605392775 isParatext "false" @default.
- W1605392775 isRetracted "false" @default.
- W1605392775 magId "1605392775" @default.
- W1605392775 workType "article" @default.