1993 Fiscal Year Final Research Report Summary
RESEARCH IN THE PATHOGENESIS OF MOTOR NEURON DISEASES.ANALYSIS OF CHOLINE ACETYLTRANSFERASE GENE EXPRESSION IN SPINAL MOTOR NEURON.
| Project/Area Number |
04670480
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Neurology
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| Research Institution | HOKKAIDO UNIVERSITY |
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Principal Investigator |
MORIWAKA Fumio HOKKAIDO UNIVERSITY HOSPITAL ASSOCIATE PROFESSOR, 医学部・附属病院, 助教授 (30142722)
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| Co-Investigator(Kenkyū-buntansha) |
TASHIRO Kunio HOKKAIDO UNIVERSITY HOSPITAL PROFESSOR, 医学部・附属病院, 教授 (90002154)
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| Project Period (FY) |
1992 – 1993
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| Keywords | MOTOR NEURON DISEASE / AMYOTROPHIC LATERAL SCLEROSIS / CHOLINE ACETYLTRANSFERASE / EXTERNAL FACTORS / POLIO VIRUS / MERCURY |
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| Research Abstract |
MOTOR NEURON DISEASE (NMD) INCLUDING AMYOTROPHIC LATERAL SCLEROSIS (ALS) IS STILL CAUSED UNKNOWN.IN THE CHOLINERGIC NEURONS INCLUDING alha -MOTOR NEURONS.CHOLINE ACETYLTRANSFERASE (ChAT) PLAYS A IMPORTANT ROLE.WE AIMED TO ANALIZE THE EXPRESSION OF ChAT GENE IN THE DEVELOPMENTAL RAT SPINAL CORD.FURTHERMORE, IN CORRELATION OF POLIO VIRUS AND MERCURY.THE PATHOGENESIS OF MND WAS STUDIED.
ACCORDING TO THE AMINO ACID SEQUENCES OF PROCAINE ChAT cDNA, 122-MER OLIGONUCLEOTIDE WAS SYNTHESIZED AND USED AS A PRIMER TO LABEL THE DNA.THE DNA WAS LABELED WITH [^<32>P] ATP AND [^<32>P] CTP FOR SCREENING A RAT GENOMIC LIBRARY.
AN EXON WAS IDENTIFIED AND SEQUENCED.AND A GENOMIC FRAGMENT WAS USED AS A PROBE FOR DETECTING ChAT TRANSCRIPTS IN THE SPINAL CORD.
ChAT ACTIVITIES WERE ESTIMATED AS 0.41 (〕SY.+-.〔) 0.27 P MOLE/MIN./CORD AND 0.86 (〕SY.+-.〔) 0.62 P MOLE/MIN./CORD.IN 12TH - 14TH AND 16TH - 18TH RAT FETAL SPINAL CORD.RESPECTIVELY.THESE VALUES WERE CONSISTENT WITH THE FETAL MATURATION AND DEVELOPMENT.THE ANALYSIS OF ChAT cDNA IS STILL GOING ON.THE ESTABLISHED IN SITU HYBRIDIZATION METHOD UTILIZING NON-RADIOACTIVE PROBRS SEEMED TO BE MORE SUITABLE IN THE DETECTION OF THE ChAT GENE EXPRESSION.
THE ANALYSIS OF THE GEOGRAPHIC DISTRIBUTIONS OF 389 CASES WITH MND FOR THE PERIOD 1980 - 1989 AND 2,171 CASES WITH POLIOMYELITIS BETWEEN 1949 - 1958 SHOWED NO SIGINIFICANT CORRELATION.THE MEASUREMENTS OF THE MERCURY AND SELENIUM IN 21 SPORADIC ALS AND 36 CONTROLS REVEALED THAT MERCURY AND SELENIUM LEVELS IN PLASMA AND BLOOD CELLS OF ALS PATIENTS WERE SIGNIFICANT LOWER IN ADVANCED STAGED ALS PATIENTS THAN CONTROLS.LOW MERCURY AND SELENIUM CONTENTS IN ALS.BEING CORRELATED WITH THEIR DISABILITIES AND NUTRITIONAL CONDITIONS, WOULD RATHER REFLECT THE DISEASE CONTRACTED STATES THAN THE PATHOGENIC ROLES IN ALS.
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