Annual report : National Institute of Neurological Disorders and Stroke

National Institute Of Neurological Disorders And Stroke (U.S.)

Sujets

• Cerebrovascular disease
• Nervous system

Informations

• Publié par: les_archives_du_savoir
• Nombre de lectures: 7
• Langue: English
• Poids de l'ouvrage: 11 Mo

Extrait

ANNUAL REPORT
INTRAMURAL RESEARCH
NATIONAL INSTITUTE OF
NEUROLOGICAL DISORDERS AND STROKE
FY 1995
-(OCT. 1. 1994 SEPT. 30, 1995>'M;.^^M
n*PROJECTNUMBERDEPARTMENTOF -HEALTHANDHUMAN PUBLICHEALTH SERVICESERVICES
NOTICE OFINTRAMURALRESEARCH PROJECT
Z01 NS 02905-02 BPS
PERIODCOVERED
October 1, 1994 to September 30, 1995
OFTITLE PROJECT (so characters or less. Title must fit on one line borders.)between the
Effect of B-Amyloid on Ion TransportAcross Cell Membranes
PRINCIPAL INVESTIGATOR (List other professional personnel below the Principal Investigator.) (Name, title, laboratory, and institute affiliation)
PI: G.Ehrenstein,Ph.D. Chief, BPS BPS, NINDS
Others: A. Mbuyi-Kalala, D.Sc Visiting Associate BPS,
COOPERATING UNITS (ifany)
Instrumentation and Computer Section, NINDS (D. Lange)
Laboratory of Neurosciences, NIA Fukuyama, K.C. Wadhwani, Rapoport)(Z. Galdzicki, R. S.I.
LAb/BRANCH
Basic Neurosciences Program, IRP
SEaiON
Biophysics Section
INSTITUTE ANDLOCATION
NINDS, NIH, Bethesda, Maryland 20892
TOTAL STAFF YEARS: OTHER:PROFESSIONAL:
0.41.4 1.0
CHECKAPPROPRIATE BOX(ES)
(a) Human subjects
I I (b) Human tissues (c) Neither
I I Q
(a1) Minors
I I
(a2) Interviews
I I
SUMMARY OFWORK (Usestandardunreduced type. Donotexceedthespaceprovided.)
We have previously shown that the incubation of PCI 2 pheochromocytoma cells with g-amyloid for 24
in the choline conductance of the cells. If a similar effert occurs inhours causes a significant increase
cholinergic neurons of patients with Alzheimer's disease (AD), the leakage of choline out of the
secretion of acetylcholine . This scenario has two importantneurons would decrease synthesis and
concentration of acetylcholineimplications. First, the decreased secretion could explain the decreasedfound in the brains ofAD patients. Second, in view of recent evidence that a decrease in
concentration an increase in production, there would be positive feedback,betweencauses B-amyloid
concentration. We have developed adecreased acetylcholine concentration and increased 6-amyloid
mathematical model that includes this positive feedback. According to the model, acetylcholine
sensitive the rate of production ofconcentration declines with age in a manner that is very to B-
ofamyloid. For example, 10% increase in the rate of g-amyloid production can lower the age onseta
of which the acetylcholine concentration declines to half of its initial value,AD, modeled as the age at
variability of the age of onset offrom 110 years to 60 years. This sensitivity could explain the wide
sporadic AD.
INSTITUTES OF HEALTHNATIONAL
NIH LIBRARY
FEB 2 1996
ID CENTER DR.BLDG 10,
MD 20892-1150BETHESDA,
PHS 6040 (Rev. 5/92)Cl(^
iHPROJECTNUMBERDEPARTMENTOF HEALTHANDHUMAN -SERVICES PUBLICHEALTH SERVICE
NOTICE OF INTRAMURALRESEARCH PROJECT
Z01 NS 02709-10 BPS
PERIODCOVERED
October 1, 1994 to September 30, 1995
ECT characters or less. Title must fiton one line between tMrders.)TITLE OF PROJ (so the
Secretion of Neurotransmitters and Hormones
PRINCIPAL INVESTIGATOR (List other professional personnelbelow the Principal Investigator.) (Name, title, laboratory, and institute affiliation)
Ph.D. BPS, NINDSPI: G.Ehrenstein, Chief, BPS
Others: A. Mbuyi-Kalala, D.Sc. Visiting Associate BPS,
BPS, NINDSM.Jia, M.D.
COOPERATING UNITS (ifany)
Mayo Clinic, Rochester,MN (L.A. Fitzpatrick)
Naval Medical Research Inst., Bethesda,MD (S.L. Pocotte)
LAB/BRANCH
Basic Neurosciences Program, IRP
SEaiON
Biophysics Section
INSTITUTEAND LOCATION
NINDS, NIH, Bethesda, Maryland 20892
OTHER:TOTAL STAFF YEARS: PROFESSIONAL:
0.31.21.5
CHECKAPPROPRIATE BOX(ES)
Human subjects(a) [x[]
I I (b) Human tissues Neither
I I (0
(a1) Minors
I I
(a2) Interviews
I I
WORK standardunreduced type. Donotexceed the space provided.)SUMMARY OF (Use
cells contain voltage-independent calciumWe have previously presented evidence that parathyroid
for calcium to enter thethat the function of these channels is to provide a pathwaychannels and
of parathyroid hormone (PTH). We haveintracellular compartment and affect the rate of secretion
antagonists to confirmin the presence of various channels agonists andnow measured PTH secretion
of either of the Bay-K-8644 or + )202-791the presence of the calcium channels. Addition (
antagonist (-)202-791uptake and reduced PTH secretion, whereas theresulted in increased
PTH secretion. Also depolarization of parathyroid cellscaused reduced calcium uptake and increased
solution increased PTH secretion, and this increasedby applying 50 mM potassium to the extracellular
(-)202-791agonist( + )202-791 or the antagonist . This suggestssecretion was not altered by either the
calcium concentration enough todepolarization was to reduce the intracellularthat the effect of
antagoniststhe experiments with the calcium channel agonists andsaturate PTH secretion. Overall,
PTHin parathyroid cells and their role in affectingconfirmed the presence of calcium channels
secretion.
PHS 6040 (Reu. 5/92)4Q
iPROJECTNUMBERDEPARTMENT -OF HEALTHANDHUMAN SERVICES PUBLICHEALTH SERVICE
NOTICE OFINTRAMURALRESEARCH PROJECT
Z01 NS 02218-20 BPS
PERIODCOVERED
October , 1994 to1 September 30, 1995
TITLE OF PROJECT (so characters or less. Title must fit on one line between the borders.)
Sources and Effects of Reactive Oxygen Intermediates in the Brain
PRINCIPAL INVESTIGATOR (List other professional personnel below the Principal Investigator.) (Name, title, laboratory, and institute affiliation)
PI: D. L Gilbert, Ph.D. Research Physiologist BPS, NINDS
Others: J.Snell,M.S. Pre-IRTA BPS,
COOPERATING UNITS (ifany)
Georgetown University, Washington, DC (C. A. Colton, O. Chernyshev)
LAB/BRANCH
Basic Neurosciences Program, IRP
SEaiON
Biophysics Section
INSTITUTE AND LOCATION
NINDS, NIH, Bethesda. Maryland 20892
TOTAL STAFF YEARS: OTHER:PROFESSIONAL:
0.32.3 2.0
CHECKAPPROPRIATE BOX(ES)
(a) Human subjects
I I (b) Human tissues (c) Neither
I I
(a1) Minors
I I
(a2) Interviews
I I
SUMMARY OFWORK (UseStandardunreduced type. Donotexceedthe provided.)space
Experiments have been performed on microglia and astrocytes cultured from cerebral cortices of mice
and hamsters . We have previously demonstrated that activated rat microglia cells produce the reactive
oxygen species (ROS) . superoxide radical anion, within a few hours after stimulation and nitric oxide.
after a period of about 10 hours to several days. Previously, we have also shown hamsterthat
microglia releases little or no nitric oxide. We have now shown that activated mice microglia also
produce nitric oxide. We have continued these studies using normal human microglia, obtained from
biopsy samples, and have shown that these human microglia produce little or no nitric oxide^ We have
tested more than 24 chemical activators including 6-amyloid (1-40) determine ifto any one of them
could activate hamster microglia to produce nitric oxide. Neither hamster nor human microglia
produce NO. Human microglia have only been tested with 6 different chemical activators to determine
if any of these would be successful techniques for producing nitric oxide. Thus, we have now shown
that hamster microglia are similar to human microglia, and that for animal disease models in which
microglia participate, it might be better to use hamsters instead of rats and mice. Since arginase
catalyses the breakdown of arginine into urea and ornithine, we tested whether the inhibition of this
pathway by )-S-2-amino-5-iodoacetamidopentanoic acid (AIAP), an inhibitor of the enzyme,( +
arginase, could possibly produce nitric oxide production in the hamster microglia. Preliminary
experiments, indicated that this inhibition did produce nitric oxide from stimulated hamster
microglia.The B103 cells, derived from neuroblastoma line, are exceptional in their lack of 6-amyloid
precursor protein. The cells have been grown in the presence of hydrogen peroxide oxidativeas a
stress. We are currently accessing the damage produced by this oxidative stress. We plan to give the
same oxidative stress to these cells in the presence of added 6-amyloid precursor protein and
determine if this is an antioxidant.
PHS 6040 (Rev. SI92)^
c^PROJECTNUMBERDEPARTMENTOF HEALTH -ANDHUMAN SERVICES PUBLICHEALTH SERVICE
NOTICE OFINTRAMURALRESEARCH PROJECT
Z01 NS 02890-03SMS
PERIODCOVERED
October 1994through1, September 30, 1995
TITLE OF PROJECT (so characters or less. Titlemust fiton one line between the borders.)
Calcium Channels in Vertebrate Nerve Terminals
PRINCIPALINVESTIGATOR (Listotherprofessional personnelbelow the Principal Investigator.) (Name, title, laboratory, andinstitute affiliation)
P.I. E.F.Stanley, Ph.D. Staff Physiologist SMS
others: Yuan Liu, Ph.D. Senior Staff Fellow SMS
Paul Joseph Church, Ph.D. IRTA Fellow SMS
Wolfram A. Gottschalk Pre-IRTA Fellow SMS
COOPERATING UNITS any)Of
P. Haydon, Ph.D. Department of Zoological and Molecular Biology, Univ. Iowa, Ames, lA, H. Chin, Ph.D.,
Staff Scientist, LNCNINDS
LAB/BRANCH
SEaiON
Synaptic Mechanisms Section, BNP, DIR
INSTITUTEANDLOCATION
NINDS, NIH, Bethesda, Maryland 20892.
TOTAL STAFF YEARS: OTHER:PROFESSIONAL:
4.8 4.8
CHECKAPPROPRIATE BOX(ES)
(a) Human subjects
I I |x x(