VASE-containing N-CAM isoforms are increased in the hippocampus in bipolar disorder but not schizophrenia

Marquis P. Vawter, John J. Hemperly, Thomas Hyde, Susan E. Bachus, Dale M. VanderPutten, Allyson L. Howard, H. E. Cannon-Spoor, Michael T. McCoy, Maree J. Webster, Joel Kleinman, William J. Freed

Research output: Contribution to journalArticle

Abstract

The neural cell adhesion molecule (N-CAM) is a cell recognition molecule that is involved in cellular migration, synaptic plasticity, and CNS development. In schizophrenia, a 105- to 115-kDa N-CAM protein is increased in CSF and in the hippocampus and prefrontal cortex. The variable alternatively spliced exon (VASE) of N-CAM is developmentally regulated and can be spliced into any of the major 120-, 140-, and 180-kDa N-CAM isoforms. We determined that the variable alternative spliced exon of N-CAM (VASE) also is increased in bipolar disorder by quantitative Western immunoblot. VASE immunoreactive proteins (triplet bands around 140 kDa and a single band around 145 kDa) were identified in soluble and membrane brain extracts and quantified in the hippocampus. Soluble VASE 140 kDa was increased in the hippocampus of patients with bipolar disorder as compared to controls, patients with schizophrenia, and suicide cases. Membrane-extracted VASE 140 and 145 kDa were unchanged in the same groups. Multiple 145-kDa VASE- immunoreactive proteins that also reacted to an NCAM antibody were separated by isoelectric focusing and electrophoresis followed by western immunoblotting; however, the VASE 140-kDa proteins were only weakly N-CAM immunoreactive. By immunohistochemistry, VASE colocalized with GFAP-positive astrocytes in the hippocampus. VASE immunostaining was also observed in the cytoplasm of CA4 pyramidal neurons that were positive for phosphorylated high molecular weight neurofilament and synaptophysin terminals. Thus no differences in VASE were found in patients with schizophrenia, but there was a marked increase of VASE immunoreactive proteins in bipolar disorder. It is possible that abnormal regulation of N-CAM proteins results in differing patterns of abnormal expression in neuropsychiatric disorders.

Original languageEnglish (US)
Pages (from-to)1-11
Number of pages11
JournalExperimental Neurology
Volume154
Issue number1
DOIs
StatePublished - Nov 1998
Externally publishedYes

Fingerprint

Neural Cell Adhesion Molecules
Bipolar Disorder
Exons
Hippocampus
Schizophrenia
Protein Isoforms
Proteins
Western Blotting
Synaptophysin
Neuronal Plasticity
Membranes
Intermediate Filaments
Pyramidal Cells
Isoelectric Focusing
Prefrontal Cortex
Astrocytes
Suicide
Electrophoresis
Cytoplasm
Molecular Weight

Keywords

  • Bipolar disorder
  • Hippocampus
  • Immunohistochemistry
  • In situ hybridization histochemistry
  • Isoelectric focusing
  • Neural cell adhesion molecule
  • Prefrontal cortex
  • Schizophrenia
  • Variable alternative spliced exon
  • Western immunoblot

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience

Cite this

Vawter, M. P., Hemperly, J. J., Hyde, T., Bachus, S. E., VanderPutten, D. M., Howard, A. L., ... Freed, W. J. (1998). VASE-containing N-CAM isoforms are increased in the hippocampus in bipolar disorder but not schizophrenia. Experimental Neurology, 154(1), 1-11. https://doi.org/10.1006/exnr.1998.6889

VASE-containing N-CAM isoforms are increased in the hippocampus in bipolar disorder but not schizophrenia. / Vawter, Marquis P.; Hemperly, John J.; Hyde, Thomas; Bachus, Susan E.; VanderPutten, Dale M.; Howard, Allyson L.; Cannon-Spoor, H. E.; McCoy, Michael T.; Webster, Maree J.; Kleinman, Joel; Freed, William J.

In: Experimental Neurology, Vol. 154, No. 1, 11.1998, p. 1-11.

Research output: Contribution to journalArticle

Vawter, MP, Hemperly, JJ, Hyde, T, Bachus, SE, VanderPutten, DM, Howard, AL, Cannon-Spoor, HE, McCoy, MT, Webster, MJ, Kleinman, J & Freed, WJ 1998, 'VASE-containing N-CAM isoforms are increased in the hippocampus in bipolar disorder but not schizophrenia', Experimental Neurology, vol. 154, no. 1, pp. 1-11. https://doi.org/10.1006/exnr.1998.6889
Vawter, Marquis P. ; Hemperly, John J. ; Hyde, Thomas ; Bachus, Susan E. ; VanderPutten, Dale M. ; Howard, Allyson L. ; Cannon-Spoor, H. E. ; McCoy, Michael T. ; Webster, Maree J. ; Kleinman, Joel ; Freed, William J. / VASE-containing N-CAM isoforms are increased in the hippocampus in bipolar disorder but not schizophrenia. In: Experimental Neurology. 1998 ; Vol. 154, No. 1. pp. 1-11.
@article{a9ca0b2669c34a388b7660e5b7714267,
title = "VASE-containing N-CAM isoforms are increased in the hippocampus in bipolar disorder but not schizophrenia",
abstract = "The neural cell adhesion molecule (N-CAM) is a cell recognition molecule that is involved in cellular migration, synaptic plasticity, and CNS development. In schizophrenia, a 105- to 115-kDa N-CAM protein is increased in CSF and in the hippocampus and prefrontal cortex. The variable alternatively spliced exon (VASE) of N-CAM is developmentally regulated and can be spliced into any of the major 120-, 140-, and 180-kDa N-CAM isoforms. We determined that the variable alternative spliced exon of N-CAM (VASE) also is increased in bipolar disorder by quantitative Western immunoblot. VASE immunoreactive proteins (triplet bands around 140 kDa and a single band around 145 kDa) were identified in soluble and membrane brain extracts and quantified in the hippocampus. Soluble VASE 140 kDa was increased in the hippocampus of patients with bipolar disorder as compared to controls, patients with schizophrenia, and suicide cases. Membrane-extracted VASE 140 and 145 kDa were unchanged in the same groups. Multiple 145-kDa VASE- immunoreactive proteins that also reacted to an NCAM antibody were separated by isoelectric focusing and electrophoresis followed by western immunoblotting; however, the VASE 140-kDa proteins were only weakly N-CAM immunoreactive. By immunohistochemistry, VASE colocalized with GFAP-positive astrocytes in the hippocampus. VASE immunostaining was also observed in the cytoplasm of CA4 pyramidal neurons that were positive for phosphorylated high molecular weight neurofilament and synaptophysin terminals. Thus no differences in VASE were found in patients with schizophrenia, but there was a marked increase of VASE immunoreactive proteins in bipolar disorder. It is possible that abnormal regulation of N-CAM proteins results in differing patterns of abnormal expression in neuropsychiatric disorders.",
keywords = "Bipolar disorder, Hippocampus, Immunohistochemistry, In situ hybridization histochemistry, Isoelectric focusing, Neural cell adhesion molecule, Prefrontal cortex, Schizophrenia, Variable alternative spliced exon, Western immunoblot",
author = "Vawter, {Marquis P.} and Hemperly, {John J.} and Thomas Hyde and Bachus, {Susan E.} and VanderPutten, {Dale M.} and Howard, {Allyson L.} and Cannon-Spoor, {H. E.} and McCoy, {Michael T.} and Webster, {Maree J.} and Joel Kleinman and Freed, {William J.}",
year = "1998",
month = "11",
doi = "10.1006/exnr.1998.6889",
language = "English (US)",
volume = "154",
pages = "1--11",
journal = "Experimental Neurology",
issn = "0014-4886",
publisher = "Academic Press Inc.",
number = "1",

}

TY - JOUR

T1 - VASE-containing N-CAM isoforms are increased in the hippocampus in bipolar disorder but not schizophrenia

AU - Vawter, Marquis P.

AU - Hemperly, John J.

AU - Hyde, Thomas

AU - Bachus, Susan E.

AU - VanderPutten, Dale M.

AU - Howard, Allyson L.

AU - Cannon-Spoor, H. E.

AU - McCoy, Michael T.

AU - Webster, Maree J.

AU - Kleinman, Joel

AU - Freed, William J.

PY - 1998/11

Y1 - 1998/11

N2 - The neural cell adhesion molecule (N-CAM) is a cell recognition molecule that is involved in cellular migration, synaptic plasticity, and CNS development. In schizophrenia, a 105- to 115-kDa N-CAM protein is increased in CSF and in the hippocampus and prefrontal cortex. The variable alternatively spliced exon (VASE) of N-CAM is developmentally regulated and can be spliced into any of the major 120-, 140-, and 180-kDa N-CAM isoforms. We determined that the variable alternative spliced exon of N-CAM (VASE) also is increased in bipolar disorder by quantitative Western immunoblot. VASE immunoreactive proteins (triplet bands around 140 kDa and a single band around 145 kDa) were identified in soluble and membrane brain extracts and quantified in the hippocampus. Soluble VASE 140 kDa was increased in the hippocampus of patients with bipolar disorder as compared to controls, patients with schizophrenia, and suicide cases. Membrane-extracted VASE 140 and 145 kDa were unchanged in the same groups. Multiple 145-kDa VASE- immunoreactive proteins that also reacted to an NCAM antibody were separated by isoelectric focusing and electrophoresis followed by western immunoblotting; however, the VASE 140-kDa proteins were only weakly N-CAM immunoreactive. By immunohistochemistry, VASE colocalized with GFAP-positive astrocytes in the hippocampus. VASE immunostaining was also observed in the cytoplasm of CA4 pyramidal neurons that were positive for phosphorylated high molecular weight neurofilament and synaptophysin terminals. Thus no differences in VASE were found in patients with schizophrenia, but there was a marked increase of VASE immunoreactive proteins in bipolar disorder. It is possible that abnormal regulation of N-CAM proteins results in differing patterns of abnormal expression in neuropsychiatric disorders.

AB - The neural cell adhesion molecule (N-CAM) is a cell recognition molecule that is involved in cellular migration, synaptic plasticity, and CNS development. In schizophrenia, a 105- to 115-kDa N-CAM protein is increased in CSF and in the hippocampus and prefrontal cortex. The variable alternatively spliced exon (VASE) of N-CAM is developmentally regulated and can be spliced into any of the major 120-, 140-, and 180-kDa N-CAM isoforms. We determined that the variable alternative spliced exon of N-CAM (VASE) also is increased in bipolar disorder by quantitative Western immunoblot. VASE immunoreactive proteins (triplet bands around 140 kDa and a single band around 145 kDa) were identified in soluble and membrane brain extracts and quantified in the hippocampus. Soluble VASE 140 kDa was increased in the hippocampus of patients with bipolar disorder as compared to controls, patients with schizophrenia, and suicide cases. Membrane-extracted VASE 140 and 145 kDa were unchanged in the same groups. Multiple 145-kDa VASE- immunoreactive proteins that also reacted to an NCAM antibody were separated by isoelectric focusing and electrophoresis followed by western immunoblotting; however, the VASE 140-kDa proteins were only weakly N-CAM immunoreactive. By immunohistochemistry, VASE colocalized with GFAP-positive astrocytes in the hippocampus. VASE immunostaining was also observed in the cytoplasm of CA4 pyramidal neurons that were positive for phosphorylated high molecular weight neurofilament and synaptophysin terminals. Thus no differences in VASE were found in patients with schizophrenia, but there was a marked increase of VASE immunoreactive proteins in bipolar disorder. It is possible that abnormal regulation of N-CAM proteins results in differing patterns of abnormal expression in neuropsychiatric disorders.

KW - Bipolar disorder

KW - Hippocampus

KW - Immunohistochemistry

KW - In situ hybridization histochemistry

KW - Isoelectric focusing

KW - Neural cell adhesion molecule

KW - Prefrontal cortex

KW - Schizophrenia

KW - Variable alternative spliced exon

KW - Western immunoblot

UR - http://www.scopus.com/inward/record.url?scp=0032211307&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032211307&partnerID=8YFLogxK

U2 - 10.1006/exnr.1998.6889

DO - 10.1006/exnr.1998.6889

M3 - Article

C2 - 9875262

AN - SCOPUS:0032211307

VL - 154

SP - 1

EP - 11

JO - Experimental Neurology

JF - Experimental Neurology

SN - 0014-4886

IS - 1

ER -