Selective complexing of acetylcholinesterase in brain by intravenously administered monoclonal antibody

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Rats injected intravenously with monoclonal antibodies reactive with brain acetylcholinesterase (AChE) developed a prolonged depression of plasma AChE without changes in butyrylcholinesterase, lactic acid dehydrogenase, or hematocrit. One antibody, ZR1, accumulated in the brain and spinal cord. Within 3 days of injection, ZR1 bound to most of the AChE in cerebral cortex and certain other regions of the CNS. Examination of the molecular forms of cortical AChE showed that antibody binding in vivo was selective for 10S AChE, whereas 4S AChE remained free. In vitro, however, ZR1 bound equally to solubilized 4S and 10S forms. These data provide direct evidence for the compartmentalization of different AChE forms in the CNS, 10S being mainly extracellular and 4S apparently intracellular. Development of a striking and persistent bilateral ptosis within hours of injection suggests that AChE in the autonomic nervous system is also accessible to antibodies and, furthermore, is the site of an immunopathological lesion. This novel model of cholinergic autoimmunity may have relevance for human neurological disorders of unknown etiology.

Original languageEnglish (US)
Pages (from-to)236-241
Number of pages6
JournalJournal of Neurochemistry
Volume54
Issue number1
DOIs
StatePublished - 1990

Fingerprint

Acetylcholinesterase
Brain
Monoclonal Antibodies
Antibodies
Butyrylcholinesterase
Injections
Autonomic Nervous System
Neurology
Nervous System Diseases
Autoimmunity
Hematocrit
Cerebral Cortex
Cholinergic Agents
Rats
Lactic Acid
Spinal Cord
Oxidoreductases
Plasmas

Keywords

  • Acetylcholinesterase
  • Autoimmune neurological disease
  • Blood-brain barrier
  • Brain
  • Dysautonomia
  • Molecular forms

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Selective complexing of acetylcholinesterase in brain by intravenously administered monoclonal antibody. / Brimijoin, William Stephen; Balm, M.; Hammond, P.; Lennon, Vanda A.

In: Journal of Neurochemistry, Vol. 54, No. 1, 1990, p. 236-241.

Research output: Contribution to journalArticle

@article{5277bcae4d77454580c46c0e94da6c55,
title = "Selective complexing of acetylcholinesterase in brain by intravenously administered monoclonal antibody",
abstract = "Rats injected intravenously with monoclonal antibodies reactive with brain acetylcholinesterase (AChE) developed a prolonged depression of plasma AChE without changes in butyrylcholinesterase, lactic acid dehydrogenase, or hematocrit. One antibody, ZR1, accumulated in the brain and spinal cord. Within 3 days of injection, ZR1 bound to most of the AChE in cerebral cortex and certain other regions of the CNS. Examination of the molecular forms of cortical AChE showed that antibody binding in vivo was selective for 10S AChE, whereas 4S AChE remained free. In vitro, however, ZR1 bound equally to solubilized 4S and 10S forms. These data provide direct evidence for the compartmentalization of different AChE forms in the CNS, 10S being mainly extracellular and 4S apparently intracellular. Development of a striking and persistent bilateral ptosis within hours of injection suggests that AChE in the autonomic nervous system is also accessible to antibodies and, furthermore, is the site of an immunopathological lesion. This novel model of cholinergic autoimmunity may have relevance for human neurological disorders of unknown etiology.",
keywords = "Acetylcholinesterase, Autoimmune neurological disease, Blood-brain barrier, Brain, Dysautonomia, Molecular forms",
author = "Brimijoin, {William Stephen} and M. Balm and P. Hammond and Lennon, {Vanda A}",
year = "1990",
doi = "10.1111/j.1471-4159.1990.tb13306.x",
language = "English (US)",
volume = "54",
pages = "236--241",
journal = "Journal of Neurochemistry",
issn = "0022-3042",
publisher = "Wiley-Blackwell",
number = "1",

}

TY - JOUR

T1 - Selective complexing of acetylcholinesterase in brain by intravenously administered monoclonal antibody

AU - Brimijoin, William Stephen

AU - Balm, M.

AU - Hammond, P.

AU - Lennon, Vanda A

PY - 1990

Y1 - 1990

N2 - Rats injected intravenously with monoclonal antibodies reactive with brain acetylcholinesterase (AChE) developed a prolonged depression of plasma AChE without changes in butyrylcholinesterase, lactic acid dehydrogenase, or hematocrit. One antibody, ZR1, accumulated in the brain and spinal cord. Within 3 days of injection, ZR1 bound to most of the AChE in cerebral cortex and certain other regions of the CNS. Examination of the molecular forms of cortical AChE showed that antibody binding in vivo was selective for 10S AChE, whereas 4S AChE remained free. In vitro, however, ZR1 bound equally to solubilized 4S and 10S forms. These data provide direct evidence for the compartmentalization of different AChE forms in the CNS, 10S being mainly extracellular and 4S apparently intracellular. Development of a striking and persistent bilateral ptosis within hours of injection suggests that AChE in the autonomic nervous system is also accessible to antibodies and, furthermore, is the site of an immunopathological lesion. This novel model of cholinergic autoimmunity may have relevance for human neurological disorders of unknown etiology.

AB - Rats injected intravenously with monoclonal antibodies reactive with brain acetylcholinesterase (AChE) developed a prolonged depression of plasma AChE without changes in butyrylcholinesterase, lactic acid dehydrogenase, or hematocrit. One antibody, ZR1, accumulated in the brain and spinal cord. Within 3 days of injection, ZR1 bound to most of the AChE in cerebral cortex and certain other regions of the CNS. Examination of the molecular forms of cortical AChE showed that antibody binding in vivo was selective for 10S AChE, whereas 4S AChE remained free. In vitro, however, ZR1 bound equally to solubilized 4S and 10S forms. These data provide direct evidence for the compartmentalization of different AChE forms in the CNS, 10S being mainly extracellular and 4S apparently intracellular. Development of a striking and persistent bilateral ptosis within hours of injection suggests that AChE in the autonomic nervous system is also accessible to antibodies and, furthermore, is the site of an immunopathological lesion. This novel model of cholinergic autoimmunity may have relevance for human neurological disorders of unknown etiology.

KW - Acetylcholinesterase

KW - Autoimmune neurological disease

KW - Blood-brain barrier

KW - Brain

KW - Dysautonomia

KW - Molecular forms

UR - http://www.scopus.com/inward/record.url?scp=0025164894&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0025164894&partnerID=8YFLogxK

U2 - 10.1111/j.1471-4159.1990.tb13306.x

DO - 10.1111/j.1471-4159.1990.tb13306.x

M3 - Article

C2 - 2293614

AN - SCOPUS:0025164894

VL - 54

SP - 236

EP - 241

JO - Journal of Neurochemistry

JF - Journal of Neurochemistry

SN - 0022-3042

IS - 1

ER -