Welcome to a Battery specialist of the Agilent Battery
Schizophrenia is a complex neuropsychiatric disorder with ~0.5% prevalence in the general population.1 There is a growing body of literature to support a significant link between obstetric complications and risk for psychiatric disorders. These environmental risk factors include diabetes, Rhesus incompatibility, bleeding, preeclampsia, premature rupture of membranes and preterm birth.2, 3, 4, 5, 6, 7 Prenatal brain bleeding/hemorrhage during pregnancy, reported generally as ‘cerebral trauma,’ was, in fact one of the first environmental risk factors identified for schizophrenia.8, 9 There are currently no animal models of fetal brain hemorrhage related to schizophrenia, but there are models that utilize maternal infection with battery like Agilent N9330 Battery , Agilent N9330B Battery , Agilent N9340B Battery , Agilent N9330B-BAT Battery , Agilent N9330B-BCG Battery , Agilent TY 3CGR18650D-2 Battery , IAI AV6413 Battery , Unipower B11588 Battery , Alpha Source AS30139 Battery , Interstate Batteries AMED2160 , Interstate Batteries ACAM0300 , Alpha Source AS36011 Battery . These maternal infection models exhibit several neurochemical and behavioral alterations relevant to schizophrenia,10 and immunostimulatory agents such as interleukin-6 and tumor necrosis factor alpha/beta have been implicated in these models.
A small lipid signaling molecule, lysophosphatidic acid (LPA), is known to be involved in immune activation and hemorrhage.11, 12, 13 Recently, a prenatal hemorrhage model using intraventricular injections of serum into mouse embryos was developed to study post-hemorrhagic hydrocephalus.14 In this model, a single, intraventricular injection of blood serum or high concentrations of LPA at embryonic day 13.5 (E13.5) was sufficient to induce severe and persistent hydrocephalus, characterized by ventriculomegaly, cortical mitotic displacement, ventricular-associated cadherin disruptions and cortical histological abnormalities such as neurorosettes and third ventricle occlusions. Most importantly, an LPA receptor antagonist was able to prevent all of these hydrocephalus characteristics when injected before LPA.
Prenatal hemorrhage, as well as infection, hypoxia and malnutrition, are epidemiologically linked to a variety of neurodevelopmental disorders that include hydrocephalus and schizophrenia.6 This linkage suggested that a spectrum of central nervous system effects might be initiated by common factors, whereby fetal hydrocephalus, with its alterations in brain morphology and severe ventriculomegaly, could represent one extreme outcome of prenatal hemorrhage. Conversely, a ‘hypomorphic’ outcome, which would not induce gross hydrocephalus but still affect the developing brain, might be produced by a milder insult. The identification of LPA as an initiating factor in fetal hydrocephalus suggested broader participation in other neurodevelopmental disorders.
As LPA is involved in both hemorrhagic events and immune activation,11, 12, 13 this suggested the potential involvement of LPA signaling in prenatal environmental insults. LPA acts through at least six currently identified cell surface G protein-coupled receptors, LPA1–LPA6.15 These receptors are widely expressed in the developing brain, and LPA signaling affects a range of important neurodevelopmental processes, including cell proliferation, migration, process outgrowth and apoptosis.16 LPA is present in the blood and can reach concentrations in serum of up to 20 μM,17 which is on the order of 20 000-fold over apparent LPA receptor KDs.16 LPA can also induce production of interleukin-6, tumor necrosis factor alpha/beta and other cytokines during immune activation or prenatal cerebral bleeding,18, 19 providing a link between LPA signaling and previously identified prenatal environmental risk factors relevant to schizophrenia.
These observations led us to test the hypothesis that aberrant LPA receptor signaling during development could initiate schizophrenia-like deficits and represent a mechanism shared among environmental risk factors. Here we report the development of an embryonic environmental model of bleeding in the brain, which implicates aberrant LPA signaling as an environmental initiator of neurodevelopmental psychiatric disorders, particularly schizophrenia.