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Tolga Uz
received his M.D. degree in 1989 from Ege University Medical School
in Izmir, Turkey. After a brief career as a Primary Care Physician,
Dr. Uz attended a Ph.D. program in neurophysiology at the Ege University,
School of Medicine, Department of Physiology. Dr. Uz has done experimental
work of his thesis in Allegheny Singer Research Institute in Pittsburgh,
PA and Psychiatric Institute, Department of Psychiatry at the University
Illinois, Chicago, IL under the supervision of Dr. Hari Manev. Dr. Uz
obtained his Ph.D. degree in 1999 (Thesis: The Role of Neuronal 5-Lipoxygenase
in Aging Associated Neurodegeneration). He has continued his postdoctoral
studies as a Visiting Scientist in the laboratory of Dr. Hari Manev,
at the Psychiatric Institute, Department of Psychiatry at the University
Illinois, Chicago, where he currently works on projects concerning the
role of 5-lipoxygenase in the Central Nervous System. In January 2001,
Dr. Uz was appointed Research Assistant Professor.
Role
of serotonin N-acetyltransferase in cocaine-induced behaviors
The abuse
of psychostimulant drugs, such as cocaine and metamphetamine, continues
to be a major public health issue in the United States. The use of inbred
mouse strains in drug addiction studies has brought new understanding
of how genetic background differences affect drug-induced behaviors.
It was recently discovered that the C57BL/6J mouse strain has a natural
single base mutation in the gene encoding the serotonin metabolizing
enzyme arylalkylamine N-acetyltransferase (5-HT N-acetyltransferase;
AANAT). This single base mutation results in the activation of a cryptic
acceptor splice sequence and the inclusion of a pseudo-exon in the mature
mRNA. A random premature stop codon inside this peudo-exon causes truncation
of AANAT protein that lacks normal function; i.e., it cannot metabolize
serotonin into N-acetylserotonin (NAS).
The primary
site of NAS synthesis is the pineal gland in which AANAT expression
and NAS synthesis are regulated in the manner of circadian rhythms (low
during the day, high at night). AANAT is also expressed in the brain
but this expression is not affected by circadian rhythms. In the pineal
gland, NAS can also be converted into melatonin. Psychostimulant cocaine
increases the enzymatic activity of AANAT and the synthesis of NAS and
melatonin. NAS and melatonin may act by binding to high affinity melatonin
or serotonin receptors in the brain. It has been reported that repeated
co-administrations of melatonin and cocaine prevented the development
of cocaine-induced locomotor sensitization, which is considered a model
for cocaine addiction.
Since AANAT-mutant
C57BL/6J mice tolerate cocaine better and are more prone to develop
cocaine-induced sensitization than AANAT-normal mice we hypothesize
that a) brain and/or pineal AANAT gene expression is crucially involved
in the neurobiological effects of cocaine (e.g. sensitization); and
b) the AANAT/NAS/melatonin system might be a therapeutic target for
agents that would prevent cocaine abuse.
Education
- Ph.D.
in "Neurophysiology"; 1993 - 1999, Ege University, School
of Medicine, Department of Physiology, Izmir, Turkey
- Thesis:
"The Role of Neuronal 5-Lipoxygenase in Aging Associated
Neurodegeneration"
- Medical
Doctor; 1983 - 1989, Ege University, School of Medicine, Izmir, Turkey
Employment
- 2001
- present: Research Assistant Professor,
Department of Psychiatry, Psychiatric Institute, University of Illinois
at Chicago, Chicago, IL
- 1996
- 2000: Research Fellow; "Neurodegenerative Disorders and Aging
Program", Department of Psychiatry, Psychiatric Institute,
University of Illinois at Chicago, Chicago, IL
- 1995
- 1996: Research Fellow; "Neuroplasticity in Aging Program",
Allegheny-Singer Research Institute, Medical College of Pennsylvania
and Hahnemann University, Pittsburgh, PA
- 1993
- 1997: Research Assistant, Ege University School of Medicine, Department
of Physiology, and Ege University Center for Brain Research, Izmir,
Turkey
- 1990
- 1993: PCP, Turkish Ministry of Health, Primary Health Center, Izmir,
Turkey
- 1989
- 1990: PCP, Turkish Ministry of Health, Primary Health Center, Ordu,
Turkey
Memberships
- International
Brain Research Organization (1992)
- Turkish
Neuroscience Society (1992)
- Turkish
Society of Physiological Sciences (1992)
- Society
for Neuroscience (1996)
- Pittsburgh
Neuroscience Society (1996)
- New
York Academy of Sciences (1996)
- Chicago
Chapter of the Society for Neuroscience (1996)
- American
Association for the Advancement of Science (1998)
- International
Society for Neurochemistry (2000)
Meetings
- 18th
National Congress of Physiology, Urgup, Turkey (1992)
- 1st
Turkish Neuroscience Congress, Istanbul, Turkey (1993)
- 1st
Cerebrovascular Disease Society Congress, Afyon, Turkey (1994)
- 19th
National Congress of Physiology, Izmir, Turkey (1994)
- International
Symposium on Oxidative Stress, Apoptosis and Brain Damage, Pittsburgh,
PA (1995)
- 25th
Annual Meeting of Society for Neuroscience, San Diego, CA (1995)
- 26th
Annual Meeting of Society for Neuroscience, Washington, DC (1996)
- 2nd
International Symposium on Oxidative Stress, Apoptosis and Brain Damage,
Chicago, IL (1997)
- 27th
Annual Meeting Society for Neuroscience, New Orleans, LA (1997)
- 28th
Annual Meeting Society for Neuroscience, Los Angeles, CA (1998)
- Joint
meeting of International Society for Neurochemistry and European Society
for Neurochemistry, Berlin, Germany (1999)
- 29th
Annual Meeting Society for Neuroscience, Miami Beach, FL (1999)
- 31st
Annual Meeting American Society for Neurochemistry, Chicago, IL (2000)
- 55th
Annual Convention Society of Biological Psychiatry, Chicago, IL (2000)
Courses
for Ph.D. Training
- Neurophysiology
(based on Principles of Neural Science by Kandel, Schwartz, and Jessell)
- Cellular
and Molecular Physiology and Signal Transduction
- Biostatistics
and Computer Applications
- Tissue
and Cell Culture Techniques
- Biophysics
(based on From Neuron To Brain by Nicholls, Martin, and Wallace)
Workshops
and Courses
- Basics
of Molecular Biology for Neurobiologists, Special Course 1, 25th Annual
Meeting of SFN; Nov 11, 1995; San Diego, CA
- Survival
Skills and Ethics Workshops, Grantpersonship; University of Pittsburgh,
NIH and NSF organization; Feb 24, 1996; Pittsburgh, PA
- Neurotransmitter
Release and Uptake; NATO-ASI, April 20-30, 1996, Kusadasi, Turkey
Professional
Honors
- International
Neurological Science Fellowship Award from the National Institute
of Neurological Disorders and Stroke (NINDS) in cooperation with the
World Health Organization (WHO) and the Fogarty International Center
(FIC), 1995-96 and 1996-97.
- International
Society for Neurochemistry (ISN) Travel Award from ISN Travel Awards
Committee to attend Joint Meeting of the International Society for
Neurochemistry and European Society for Neurochemistry, August 8-14,
1999, Berlin, Germany.
Number
of citations based on ISI Citation Database
Bibliography
- Cagnoli,
C. M., Kharlamov, E., Atabay, C., Uz, T., Manev, H. (1996) Apoptosis
induced in neuronal cultures by either the phosphatase inhibitor Okadaic
Acid or the kinase inhibitor Staurosporine is attenuated by Isoquinolinesulfonamides
H-7, H-8, and H-9. Journal of Molecular Neuroscience, 7, 65-76.
- Kharlamov,
A., Uz, T., Joo, J.-Y., Manev, H. (1996) Pharmacological characterization
of apoptotic cell death in a model of photothrombotic brain injury
in rats. Brain Research, 734, 1-9.
- Uz,
T., Giusti, P., Franceschini, D., Kharlamov, A., Manev, H. (1996)
Protective effect of melatonin against hippocampal DNA damage induced
by intraperitoneal administration of kainate to rats. Neuroscience,
73 (3), 631-636.
- Manev,
H., Uz, T., Kharlamov, A., Cagnoli, C.M., Franchescini, P., Giusti,
P. (1996) In vivo protection against kainate-induced apoptosis by
the pineal hormone melatonin: effect of exogenous and endogenous melatonin.
Restorative Neurology and Neuroscience,.9, 251-256.
- Manev,
H., Uz, T., Kharlamov, A., Joo, J.-Y. (1996) Increased brain damage
after stroke or excitotoxic seizures in melatonin-deficient rats.
FASEB J, 10, 1546-1551.
- Manev,
H., Uz T., Kharlamov A., Joo, J.-Y., Giusti, P., and Cagnoli C.M.
(1997) Melatonin reduces the expression of excitotoxicity-triggered
markers of apoptosis. Therapeutic Potential of Melatonin, Front
Horm Res. Basel, Karger, 23, 89-98 Eds.: Maestroni GJM, Conti
A., Reiter, R.J.
- Kharlamov,
A., Joo, J.Y., Uz, T., Manev, H. (1997) Cycloheximide reduces the
size of brain lesion caused in rats by a photothrombotic model of
stroke. Neurological Research, 19, 92-96.
- Manev,
H., Kharlamov, E., Uz, T., Mason, P.R., Cagnoli, C.M. (1997) Characterization
of Zinc-induced neuronal death in primary cultures of rat cerebellar
granule cells Experimental Neurology, 146, 171-178.
- Uz,
T., Kharlamov, A., Joo, J.-Y., Franceschini, D., Giusti, P., and Manev,
H. (1997) Kainate-induced DNA damage triggers p53 immunoreactivity
in the rat hippocampus: protection with melatonin. Croatian Medical
Journal, 38, 205-211.
- Manev,
H., Uz, T., and Giusti, P. (1997) Neuroprotective action of the pineal
hormone melatonin against excitotoxicity: Receptor Abuse-Dependent
Antagonism (RADA). Annals of the New York Academy of Sciences,
825, 85-89.
- Uz T.,
Longone, P., and Manev, H. (1997) Increased hippocampal 5-lipoxygenase
mRNA content in melatonin-deficient, pinealectomized, rats. Journal
of Neurochemistry, 69, 5, 2220-2223.
- Manev,
H., and Uz, T. (1998) The role of the light-dark cycle and melatonin
in stroke outcome. Journal of Stroke and Cerebrovascular Diseases,
7, 3, 165-167.
- Uz T.,
Pesold C., Longone P., and Manev H. (1998) Aging-associated upregulation
of neuronal 5-lipoxygenase expression: putative role in neuronal vulnerability.
FASEB J, 12, 6, 439-449.
- Manev
H., Uz, T., and Qu T. (1998) Early upregulation of hippocampal 5-lipoxygenase
following systemic administration of kainate to rats. Restorative
Neurology and Neuroscience, 12, 81-85.
- Uz,
T., and Manev, H. (1998) Circadian expression of pineal 5-lipoxygenase
mRNA. Neuroreport, 9, 5, 783-786.
- Manev,
H. and Uz, T. (1998) Regulation of brain expression of serotonin N-Acetyltransferase
mRNA: a novel mechanism in the action of antidepressant drugs. Psychiatria
Danubina, 10, 2, 165-166.
- Joo
J. Y., Uz T., and Manev H. (1998) Opposite effects of pinealectomy
and melatonin administration on DNA damage and infarct volume following
transient cerebral arteries occlusion in rats. Restorative Neurology
and Neuroscience, 13, 185-191.
- Manev,
H. and Uz, T. (1998) Oral Melatonin in neurologically disabled children.
Lancet, 351, 9120, 1963.
- Uz T.,
and Manev H. (1999) Chronic Fluoxetine administration increases the
serotonin N-Acetyltransferase mRNA content in rat hippocampus. Biological
Psychiatry, 45, 2, 175-179.
- Uz,
T., Dwivedi, Y., Savani, P., Impagnatiello, F., Pandey, G., and Manev,
H. (1999) Glucocorticoids stimulate inflammatory 5-lipoxygenase gene
expression and protein translocation in the brain. Journal of Neurochemistry,
73, 2, 693-699.
- Manev,
H. and Uz, T. (1999) Primary cultures of rat cerebellar granule cells
as a model to study neuronal 5-Lipoxygenase and FLAP gene expression.
Annals of the New York Academy of Sciences, 890, 183-190.
- Sugaya,
K., Uz, T., Kumar, V., and Manev, H. (2000) Emerging aspects of anti-inflammatory
treatments of Alzheimer's disease. Japanese Journal of Pharmacology,
82, 85-94.
- Manev,
H., Uz, T., Sugaya, K., and Qu, T. (2000) Putative role of neuronal
5-lipoxygenase in an aging brain. FASEB J, 14, 10, 1464-1469.
- Qu,
T., Uz, T., and Manev, H. (2000) Inflammatory 5-LOX and protein are
increased in brain of aging rats. Neurobiology of Aging, 21,
647-652.
- Manev,
H. Uz, T., and Qu, T. (2000) 5-lipoxygenase and cyclooxygenase mRNA
expression in rat hippocampus: early response to glutamate receptor
activation by kainate. Experimental Gerontology, 35, 1201-1209.
- Manev,
H., Uz, T., Smalheiser, N. and Manev, R., (2001) Antidepressants alter
cell proliferation in the adult brain in vivo and in neural cultures
in vitro. European Journal of Pharmacology, 411, 67-70.
- Uz,
T. and Manev, H. (2001) Prolonged swim-test immobility of serotonin
N-Acetyltransferase (AANAT)-mutant mice. Journal of Pineal Research,
30, 3, 166-171.
- Uz,
T., Manev, R., and Manev, H., (2001) 5-Lipoxygenase is required for
proliferation of immature cerebellar granule neurons in vitro. European
Journal of Pharmacology, 418, 15-22.
- Manev,
R., Uz, T., and Manev, H. (2001) Fluoxetine increases the content
of neurotrophic protein S100b in the rat hippocampus. European
Journal of Pharmacology 420, R1-R2, 2001.
- Uz,
T., Dwivedi, Y., Quele, A., Peters-Golden, M., Pandey, G., and Manev,
H. (2001) Dexamethasone upregulates 5-lipoxygenase (5LOX) expression
in primary cultures of rat cerebellar granule neurons via glucocorticoid
receptors and by stabilizing mRNA transcripts. FASEB J, in
press.
- Manev,
H., Uz, T., Manev, R. and Zhang, Z. (2001) Neurogenesis and neuroprotection
in the adult brain: Putative role for 5-lipoxygenase? Annals of
the New York Academy of Sciences in press.
Poster
and Slide Presentations
- Uz,
T., Kanit, L., Algan, O., Peker G. Ö. (1993) The effects of acute
and chronic stress on rat brain glutamate receptor binding I. Turkish
Neuroscience Congress, Istanbul University Faculty of Medicine 12th
Convention, October 12-16, Istanbul, Turkey, Poster presentation.
- Peker,
G.Ö., Kanit, L., Uz, T., Algan, O., (1995) Aged dependent alterations
in glutamate receptor binding in rat Fourth IBRO World Congress of
Neuroscience, July 9-14, Kyoto, Japan, Poster Presentation.
- Kanit,
L., Uz, T., Peker, G.Ö., Koylu, E.O., Algan, O., Demirgören,
S., Pögün, S. (1995) The effects of nitric oxide synthase
(NOS) inhibition and spatial learning on cortical glutamate receptors
in rat brain Fourth IBRO World Congress of Neuroscience, July 9-14,
Kyoto, Japan, Slide Presentation.
- Uz,
T., Algan, O., Peker, G.O., Demirtas, E., Kanit, L., Islekel, S.,
Gulmen, V., Yurtseven, T., Okur, B.E. (1995) Histopathological and
histochemical evaluation of cerebral ischemia; interaction of spatial
learning and a PAF antagonist treatment International Symposium on
Oxidative Stress, Apoptosis and Brain Damage, September 21-24, Pittsburgh,
PA, Poster presentation.
- Kharlamov,
A., Joo, J.Y., Uz, T., Manev, H. (1995) Photochemically induced brain
injury as a model of neuronal apoptosis in rats International Symposium
on Oxidative Stress, Apoptosis and Brain Damage, September 21-24,
Pittsburgh, PA, Poster presentation.
- Peker,
G.O., Uz, T., Kanit, L., Algan, O. (1995) The effects of acute and
chronic stress on rat brain glutamate receptor binding Society for
Neuroscience 25th Annual Meeting, November 11-16, San Diego, California,
Slide presentation.
- Uz,
T., Giusti, P., Franceschini, D., Kharlamov, A., Manev, H. (1996)
Protective effect of melatonin against hippocampal DNA damage induced
by intraperitoneal administration of kainate to rats Neurotransmitter
Release and Uptake; NATO ASI, April 20-30, 1996, Kusadasi, Turkey,
Poster presantation.
- Kharlamov,
A., Cagnoli, C.M., Kharlamov, E., Uz, T., Atabay, C., Manev, H. (1996)
Apoptotic action of singlet oxygen: in vitro and in vivo models of
neurotoxicity Congress on Pathology, October, Moscow, Russia, Slide
Presentation.
- Uz,
T., Kharlamov, A., Joo, J.-Y., Franceschini, D., Giusti, P., and Manev,
H. (1996) Effect of melatonin administration to rats on kainate-induced
p53 immunoreactivity, DNA damage and neuronal degeneration in the
rat brain Society for Neuroscience 26th Annual Meeting, November 16-21,
Washington, DC, Slide presentation.
- Manev,
H., Uz, T., Kharlamov, A., Cagnoli, C.M. (1996) In vitro and in vivo
prevention of neuronal apoptosis by melatonin 2nd Locarno Meeting
on Neuroendocrinoimmunology; Therapeutic potential of the pineal hormone
melatonin, May 5-8, Locarno, Italy, Slide presentation.
- Peker,
G.O., Islekel, S., Demirtas, E., Algan, O., Uz, T., Gulmen, V., Kanit,
L., Yurtseven, T., Okur, B.E and Kulali, B. (1996) The effects of
spatial learning and a Platelet Activating Factor antagonist on NADPH-Diaphorase
histochemistry and somatic evoked responses in a rat model of global
ischemia Society for Neuroscience 26th Annual Meeting, November 16-21,
Washington, DC, Slide presentation.
- Manev,
H., Uz, T., Kharlamov, A., and Joo, J.-Y. (1996) Decreased levels
of endogenous melatonin potentiate excitotoxic and stroke-induced
brain damage Society for Neuroscience 26th Annual Meeting, November
16-21, Washington, DC, Slide presentation.
- Joo,
J.-Y., Uz, T., Kharlamov, A., and Manev, H. (1996) Effect of pinealectomy
on brain injury induced in rats by reversible middle cerebral artery
occlusion Society for Neuroscience 26th Annual Meeting, November 16-21,
Washington, DC, Poster presentation.
- Manev,
H., Uz, T., and Joo, J-Y. (1997) Evidence for neuroprotective role
of the pineal hormone melatonin Joint Meeting of The International
Society for Neurochemistry and The American Society for Neurochemistry,
July 20-26, Boston, MA, Invited lecture.
- Uz,
T., Mienville, J.-M., and Manev, H. (1997) Pineal nicotinic receptors:
characterization and functional role Society for Neuroscience 27th
Annual Meeting, October 25-30, New Orleans, LA, Poster presentation.
- Manev,
H., Uz, T., Longone, P., and Pesold, C. (1997) Dual role of neuronal
5-lipoxygenase in developing neurons and in the aging brain. Society
for Neuroscience 27th Annual Meeting, October 25-30, New Orleans,
LA, Poster presentation.
- Uz,
T., Pesold, C., Longone, P., and Manev, H. (1997) Aging-associated
upregulation of neuronal 5-lipoxygenase Second International Symposium
on Oxidative Stress and Brain Damage, September 26-28, 1997, Chicago,
IL, Poster presentation.
- Uz,
T. and Manev, H. (1998) Serotonin N-Acetyltransferase (AA-NAT) mRNA
in the rat hippocampus: modifications by acute Isoproterenol and protracted
Fluoxetine treatments Society for Neuroscience 28th Annual Meeting,
November 7-12, Los Angeles, CA; Poster presentation.
- Manev,
H., Uz, T., Qu, T., Sugaya, K. (1998) Role of 5-Lipoxygenase in brain
vulnerability Fourth International Conference on Neuroprotective Agents,
Clinical and Experimental Aspects, November 15-19, Annapolis, Maryland;
Invited lecture.
- Uz,
T., Dwivedi, Y., Savani, P., Impagnatiello, F., Pandey, G., and Manev,
H. (1999) Glucocorticoids stimulate inflammatory 5-lipoxygenase gene
expression and protein translocation in the brain Joint meeting of
the International Society for Neurochemistry and European Society
for Neurochemistry, August 8-14, Berlin, Germany; J. Neurochem., suppl.
73: S209.
- Uz,
T., Dwivedi, Y., Savani, P., Impagnatiello, F., Pandey, G., and Manev,
H. (1999) Glucocorticoids stimulate the CNS 5-lipoxygenase gene expression
and protein translocation Society for Neuroscience 29th Annual Meeting,
October 23-28, Miami Beach, Florida; Poster presentation.
- Uz,
T., Grayson, R. D., and Manev, H. (2000) Expression of serotonin N-Acetyltransferase
(AANAT) mRNA in primary cultures of rat and mouse cerebellar granule
cells American Society for Neurochemistry 31st Annual Meeting, March
26-29, Chicago, Illinois, J. Neurochem., suppl. 74: S23.
- Manev,
H., Uz, T., and Manev, R. (2000) Putative role of neuronal 5-Lipoxygenase
(5-LOX) in proliferation of immature cerebellar granule cells American
Society for Neurochemistry 31st Annual Meeting, March 26-29, Chicago,
Illinois, J. Neurochem., suppl. 74: S64.
- Qu,
T., Uz, T., and Manev, H. (2000) Effect of aging on 5-Lipoxygenase
(5-LOX) mRNA and protein in the rat brain Society of Biological Psychiatry
55th Annual Meeting, May 11-13, Chicago, Illinois, Biol. Psychiatry,
47 (8 suppl 1): S136.
- Uz,
T., Dwivedi, G., Pandey, G., and Manev, H. (2000) In-vivo and in-vitro
action of glucocorticoids on neuronal 5-Lipoxygenase Society of Biological
Psychiatry 55th Annual Meeting, May 11-13, Chicago, Illinois, Biol.
Psychiatry, 47 (8 suppl 1): S137.
- Manev,
H., Uz, T., and Manev, R. (2000) Putative role of 5-lipoxygenase (5-LOX)
in neurogenesis Society of Biological Psychiatry 55th Annual Meeting,
May 11-13, Chicago, Illinois, Biol. Psychiatry, 47 (8 suppl 1): S137.
- Ho,
L., Pasinetti, G.M., Horrocks, L.A., Faroqui, A.A., Horrobin, D.F.,
Peet, M., Manev, H. and Uz, T. (2000) Eicosanoid pathways and psychiatric
disorders Society of Biological Psychiatry 55th Annual Meeting, May
11-13, Chicago, Illinois, Biol. Psychiatry, 47 (8 suppl 1): S114.
- Uz,
T., Manev, R. and Manev, H., (2000) Requirement of 5-lipoxygenase
(5-LOX) for proliferation of cerebellar granule neurons in-vitro Society
for Neuroscience 30th Annual Meeting, November 4-9, New Orleans, Louisiana;
Poster presentation.
- Koylu,
E.O., Uz, T., Manev, H. and Pogun, S. (2000) Effect of nitric oxide
synthase inhibition on physiologically and kainate-induced wet dog
shakes in rats Society for Neuroscience 30th Annual Meeting, November
4-9, New Orleans, Louisiana; Poster presentation.
- Manev,
H., Uz, T., and Manev, R. (2000) Opposite effects of antidepressants
on thymidine incorporation (proliferation) in immature and mature
cultures of rat cerebellar granule cells Serotonin: From the Molecule
to the Clinic, Official Satellite to the Society for Neuroscience
30th Annual Meeting, November 2-3, New Orleans, Louisiana; Poster
presentation.
- Uz,
T., Dwivedi, Y., Qeli, A., Peters-Golden, M., Pandey, G., and Manev,
H. (2001) Hormonal regulation of 5-Lipoxygenase (5LOX) expression
in neuronal cultures Society for Neuroscience 31th Annual Meeting,
November 10-15, San Diego, California; Poster presentation.
- Manev,
R., Uz, T., and Manev, H. (2001) Fluoxetine increases the content
of neurotrophic S100b in the rat hippocampus Society for Neuroscience
31th Annual Meeting, November 10-15, San Diego, California; Poster
presentation.
 
©2001
Department of Psychiatry
UIC 912 S. Wood Street
Chicago , IL - 60612, USA
Phone: 1-312-996-7206
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