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Title: Mapping Alterations to the Endogenous Elemental Distribution within the Lateral Ventricles and Choroid Plexus in Brain Disorders Using X-Ray Fluorescence Imaging

Journal Article · · PLoS ONE
 [1];  [1];  [2];  [3];  [1];  [4];  [5]
  1. Univ. of Saskatchewan, Saskatoon, SK (Canada)
  2. Australian Synchrotron, Clayton, VIC (Australia); La Trobe Univ., VIC (Australia)
  3. Australian Synchrotron, Clayton, VIC (Australia)
  4. Curtin Univ., Perth, WA (Australia)
  5. Argonne National Lab. (ANL), Argonne, IL (United States)

The choroid plexus and cerebral ventricles are critical structures for the production of cerebral spinal fluid (CSF) and play an important role in regulating ion and metal transport in the brain, however many aspects of its roles in normal physiology and disease states, such as psychiatric illness, remain unknown. The choroid plexus is difficult to examine in vivo, and in situ ex vivo, and as such has typically been examined indirectly with radiolabeled tracers or ex vivo stains, making measurements of the endogenous K+, Cl-, and Ca+ distributions unreliable. In the present study, we directly examined the distribution of endogenous ions and biologically relevant transition metals in the choroid plexus and regions surrounding the ventricles (ventricle wall, cortex, corpus callosum, striatum) using X-ray fluorescence imaging (XFI). We find that the choroid plexus was rich in Cl- and Fe while K+ levels increase further from the ventricle as Cl- levels decrease, consistent with the known role of ion transporters in the choroid plexus CSF production. A polyI:C offspring displayed enlarged ventricles, elevated Cl- surrounding the ventricles, and intraventricular calcifications. These observations fit with clinical findings in patients with schizophrenia and suggest maternal treatment with polyI:C may lead to dysfunctional ion regulation in offspring. Furthermore, this study demonstrates the power of XFI for examining the endogenous elemental distributions of the ventricular system in healthy brain tissue as well as disease models.

Research Organization:
Australian Synchrotron, Clayton, VIC (Australia); SLAC National Accelerator Lab., Menlo Park, CA (United States)
Sponsoring Organization:
USDOE
OSTI ID:
1377079
Journal Information:
PLoS ONE, Journal Name: PLoS ONE Journal Issue: 6 Vol. 11; ISSN 1932-6203
Publisher:
Public Library of ScienceCopyright Statement
Country of Publication:
United States
Language:
English

References (91)

Lateral Cerebral Ventricular Enlargement in Chronic Schizophrenia journal July 1979
Cerebral Ventricular Enlargement in Chronic Schizophrenia: An Association With Poor Response to Treatment journal January 1980
A Family Study of the Association of Increased Ventricular Size With Schizophrenia journal February 1986
Adult Schizophrenia Following Prenatal Exposure to an Influenza Epidemic journal February 1988
Serologic Evidence of Prenatal Influenza in the Etiology of Schizophrenia journal August 2004
Sample thickness considerations for quantitative X-ray fluorescence analysis of the soft and skeletal tissues of the human body - theoretical evaluation and experimental validation: Quantitative X-ray fluorescence analysis of human tissues journal June 2012
Mitochondrial content of choroid plexus epithelium journal October 1997
Progress of elemental anomalies of hippocampal formation in the pilocarpine model of temporal lobe epilepsy—an X-ray fluorescence microscopy study journal October 2012
Variations in elemental compositions of rat hippocampal formation between acute and latent phases of pilocarpine-induced epilepsy: an X-ray fluorescence microscopy study journal March 2012
Calcification of the choroid plexus as a marker of depression in schizophrenia journal October 1990
Abnormal Trajectories of Neurodevelopment and Behavior Following In Utero Insult in the Rat journal November 2011
Dopamine and serotonin levels following prenatal viral infection in mouse—Implications for psychiatric disorders such as schizophrenia and autism journal October 2008
A balanced view of choroid plexus structure and function: Focus on adult humans journal May 2015
Tracing the development of psychosis and its prevention: What can be learned from animal models journal March 2012
Molecular mechanisms of cerebrospinal fluid production journal January 2004
Maternal infection leads to abnormal gene regulation and brain atrophy in mouse offspring: Implications for genesis of neurodevelopmental disorders journal February 2008
Intracellular localization and subsequent redistribution of metal transporters in a rat choroid plexus model following exposure to manganese or iron journal July 2008
Cerebral Ventricular size and Cognitive Impairment in Chronic Schizophrenia journal October 1976
Choroid plexus calcification as a possible clue of serotonin implication in schizophrenia journal January 1999
X-ray Absorption Spectroscopy at the Sulfur K-Edge: A New Tool to Investigate the Biochemical Mechanisms of Neurodegeneration journal January 2012
In Situ Biospectroscopic Investigation of Rapid Ischemic and Postmortem Induced Biochemical Alterations in the Rat Brain journal November 2014
Elemental and Chemically Specific X-ray Fluorescence Imaging of Biological Systems journal January 2014
Immune Activation During Pregnancy in Rats Leads to a PostPubertal Emergence of Disrupted Latent Inhibition, Dopaminergic Hyperfunction, and Altered Limbic Morphology in the Offspring: A Novel Neurodevelopmental Model of Schizophrenia journal May 2003
Chemical alterations to murine brain tissue induced by formalin fixation: implications for biospectroscopic imaging and mapping studies of disease pathogenesis journal January 2011
Localization of copper and copper transporters in the human brain journal January 2013
X-ray fluorescence imaging reveals subcellular biometal disturbances in a childhood neurodegenerative disorder journal January 2014
High-resolution complementary chemical imaging of bio-elements in Caenorhabditis elegans journal January 2016
Uptake of 36 Cl and 22 Na by the Choroid Plexus-Cerebrospinal Fluid System: Evidence for Active Chloride Transport by the Choroidal Epithelium journal July 1981
Mechanisms of murine cerebral malaria: Multimodal imaging of altered cerebral metabolism and protein oxidation at hemorrhage sites journal December 2015
Cotransport of sodium and chloride by the adult mammalian choroid plexus journal February 1990
Chloride flux from blood to CSF: inhibition by furosemide and bumetanide journal October 1987
The role of serotonin in the pathophysiology and treatment of schizophrenia
  • Abi-Dargham, Anissa; Laruelle, Marc; Aghajanian, George K.
  • The Journal of Neuropsychiatry and Clinical Neurosciences, Vol. 9, Issue 1, p. 1-17 https://doi.org/10.1176/jnp.9.1.1
journal February 1997
A Longitudinal Examination of the Neurodevelopmental Impact of Prenatal Immune Activation in Mice Reveals Primary Defects in Dopaminergic Development Relevant to Schizophrenia journal January 2010
Choroid Plexus Calcification as a Possible Marker of Hallucinations in Schizophrenia journal January 1993
Lateral Cerebral Ventricular Enlargement in Chronic Schizophrenia journal July 1979
Cerebral Ventricular Enlargement in Chronic Schizophrenia: An Association With Poor Response to Treatment journal January 1980
A Family Study of the Association of Increased Ventricular Size With Schizophrenia journal February 1986
Adult Schizophrenia Following Prenatal Exposure to an Influenza Epidemic journal February 1988
Maternal Infections and Subsequent Psychosis Among Offspring journal November 2001
Serologic Evidence of Prenatal Influenza in the Etiology of Schizophrenia journal August 2004
Quantitative trace element imaging using PIXE and the nuclear microprobe journal January 2000
In utero infection and adult schizophrenia journal January 2002
Sample thickness considerations for quantitative X-ray fluorescence analysis of the soft and skeletal tissues of the human body - theoretical evaluation and experimental validation: Quantitative X-ray fluorescence analysis of human tissues journal June 2012
Mitochondrial content of choroid plexus epithelium journal October 1997
The Dutch Famine and schizophrenia spectrum disorders journal July 1998
Progress of elemental anomalies of hippocampal formation in the pilocarpine model of temporal lobe epilepsy—an X-ray fluorescence microscopy study journal October 2012
The role of trace elements in the pathogenesis and progress of pilocarpine-induced epileptic seizures journal August 2008
X-ray fluorescence analysis of long-term changes in the levels and distributions of trace elements in the rat brain following mechanical injury journal November 2010
Variations in elemental compositions of rat hippocampal formation between acute and latent phases of pilocarpine-induced epilepsy: an X-ray fluorescence microscopy study journal March 2012
Calcification of the choroid plexus as a marker of depression in schizophrenia journal October 1990
Cerebral Ventricular size and Cognitive Impairment in Chronic Schizophrenia journal October 1976
Birth insult interacts with stress at adulthood to alter dopaminergic function in animal models: possible implications for schizophrenia and other disorders journal January 2003
Choroid plexus calcification as a possible clue of serotonin implication in schizophrenia journal January 1999
The structure of the choroid plexus and the physiology of the choroid plexus epithelium journal October 2004
Abnormal Trajectories of Neurodevelopment and Behavior Following In Utero Insult in the Rat journal November 2011
Animal models of obstetric complications in relation to schizophrenia journal April 2004
Dopamine and serotonin levels following prenatal viral infection in mouse—Implications for psychiatric disorders such as schizophrenia and autism journal October 2008
A balanced view of choroid plexus structure and function: Focus on adult humans journal May 2015
In-vivo rodent models for the experimental investigation of prenatal immune activation effects in neurodevelopmental brain disorders journal July 2009
To poly(I:C) or not to poly(I:C): Advancing preclinical schizophrenia research through the use of prenatal immune activation models journal March 2012
Tracing the development of psychosis and its prevention: What can be learned from animal models journal March 2012
Molecular mechanisms of cerebrospinal fluid production journal January 2004
Maternal infection leads to abnormal gene regulation and brain atrophy in mouse offspring: Implications for genesis of neurodevelopmental disorders journal February 2008
Intracellular localization and subsequent redistribution of metal transporters in a rat choroid plexus model following exposure to manganese or iron journal July 2008
Prenatal immune activation leads to multiple changes in basal neurotransmitter levels in the adult brain: implications for brain disorders of neurodevelopmental origin such as schizophrenia journal August 2008
X-ray Absorption Spectroscopy at the Sulfur K-Edge: A New Tool to Investigate the Biochemical Mechanisms of Neurodegeneration journal January 2012
In Situ Biospectroscopic Investigation of Rapid Ischemic and Postmortem Induced Biochemical Alterations in the Rat Brain journal November 2014
Elemental and Chemically Specific X-ray Fluorescence Imaging of Biological Systems journal January 2014
Immune Activation During Pregnancy in Rats Leads to a PostPubertal Emergence of Disrupted Latent Inhibition, Dopaminergic Hyperfunction, and Altered Limbic Morphology in the Offspring: A Novel Neurodevelopmental Model of Schizophrenia journal May 2003
Localization of copper and copper transporters in the human brain journal January 2013
High-resolution complementary chemical imaging of bio-elements in Caenorhabditis elegans journal January 2016
Chemical alterations to murine brain tissue induced by formalin fixation: implications for biospectroscopic imaging and mapping studies of disease pathogenesis journal January 2011
Prion protein expression level alters regional copper, iron and zinc content in the mouse brain journal January 2011
X-ray fluorescence imaging reveals subcellular biometal disturbances in a childhood neurodegenerative disorder journal January 2014
The X-ray Fluorescence Microscopy Beamline at the Australian Synchrotron conference January 2011
Na + ,K + -ATPase in the Choroid Plexus: REGULATION BY SEROTONIN/PROTEIN KINASE C PATHWAY journal February 1995
Maia X-ray fluorescence imaging: Capturing detail in complex natural samples journal April 2014
Dynamic zinc pools in mouse choroid plexus journal January 2004
Aging results in copper accumulations in glial fibrillary acidic protein-positive cells in the subventricular zone journal July 2013
Uptake of 36 Cl and 22 Na by the Choroid Plexus-Cerebrospinal Fluid System: Evidence for Active Chloride Transport by the Choroidal Epithelium journal July 1981
Cerebrovascular Permeability Coefficients to Sodium, Potassium, and Chloride journal June 1986
Mechanisms of murine cerebral malaria: Multimodal imaging of altered cerebral metabolism and protein oxidation at hemorrhage sites journal December 2015
Maternal Effects on Schizophrenia Risk journal October 2007
Cotransport of sodium and chloride by the adult mammalian choroid plexus journal February 1990
Chloride flux from blood to CSF: inhibition by furosemide and bumetanide journal October 1987
Schizophrenia as a Long-Term Outcome of Pregnancy, Delivery, and Perinatal Complications: A 28-Year Follow-Up of the 1966 North Finland General Population Birth Cohort journal March 1998
Inverse Relationship Between Serotonin 5-HT 1A Receptor Binding and Anxiety: A [ 11 C]WAY-100635 PET Investigation in Healthy Volunteers journal August 2001
The role of serotonin in the pathophysiology and treatment of schizophrenia
  • Abi-Dargham, Anissa; Laruelle, Marc; Aghajanian, George K.
  • The Journal of Neuropsychiatry and Clinical Neurosciences, Vol. 9, Issue 1, p. 1-17 https://doi.org/10.1176/jnp.9.1.1
journal February 1997
X-Ray Fluorescence Imaging: A New Tool for Studying Manganese Neurotoxicity journal November 2012
A Longitudinal Examination of the Neurodevelopmental Impact of Prenatal Immune Activation in Mice Reveals Primary Defects in Dopaminergic Development Relevant to Schizophrenia journal January 2010
Choroid Plexus Calcification as a Possible Marker of Hallucinations in Schizophrenia journal January 1993

Cited By (5)

Copper signalling: causes and consequences journal October 2018
Maternal Immune Activation during Pregnancy Alters the Behavior Profile of Female Offspring of Sprague Dawley Rats journal March 2019
A Review of ex vivo Elemental Mapping Methods to Directly Image Changes in the Homeostasis of Diffusible Ions (Na+, K+, Mg2 +, Ca2 +, Cl–) Within Brain Tissue journal January 2020
Elemental characterisation of the pyramidal neuron layer within the rat and mouse hippocampus journal January 2019
Copper signalling: causes and consequences journal October 2018

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