UNIVERSIDAD DEL ESTE
Escuela de Ciencias y Tecnología
Scientific Writing
Liz M. García Peterson
Engl 315
Prof. Evelyn Lugo
Abstract:
Several mayor neurological movement disorders are currently attributed to the
malfunctioning or imbalance of specific neural pathways that use the neural transmitter
dopamine (DA). Our most effective management strategies for these incurable
disorders typically rely on agents and procedures that exert their effects on the synaptic
signaling mediated by DA. Relating the activities of neurotransmitters systems and
therapeutic agents directly to human motor control presently poses formidable
challenges. Currently, however , the task of understanding how dopaminergic cells
contribute to the control of movement may be effectively realized in animals with simpler
nervous systems, where the synaptic connections of identified neurons can be directly
examined. In view of natures conservative approach to problem-solving in neural
systems, such studies commonly lead to insights and principals that are applicable to all
complex organisms [1]. Do to its simplicity, the CNS from the snail Helisoma trivolvis
can be used to study the role of dopaminergic neurons in movement disorders. In order
to make these studies it is previously necessary to identify and localize the
dopaminergic neurons involved in control movement. In these work we used
immunohistochemical and immunoflourecense techniques to identify the dopaminergic
neurons belonging to the pedal, buccal, cerebral and abdominal ganglia (see figure 2).
We found two small clusters of dopaminergic cells in the cerebral ganglia, one large
and three small dopaminergic cells in the buccal ganglia and one large dopaminergic
cell in the pedal ganglia. These studies also revealed the absence of dopaminergic cells
in the abdominal ganglia.
Introduction:
Objectives:
- Identify and localize the dopaminergic neurons involved in control movement.
- Study the role of dopaminergic neurons in movement disorders.
Hypothesis:
Movement disorders are currently attributed to the malfunctioning or
imbalance of specific neural pathways that use the neural transmitter dopamine (DA),
that relay on effects of the synaptic signaling mediated by DA, causing movement
disorders.
Investigation Question:
- Is it possible for us to previously identify and localize the dopaminergic neurons
involved in control movement?
-
Can we understand how dopaminergic cells contribute to the control of
movement?
 Neurological movement
disorders are currently
attributed to the
malfunctioning or
imbalance of specific
neural pathways that use
the neural transmitter
dopamine (DA).
 Incurable disorders
typically rely on agents
and procedures that
exert their effects on the
synaptic signaling
mediated by DA.
TH Synthesis
In our work we use TH, to identify Dopamine because TH is the enzyme that catalyzes
Dopa and is a precursor for Dopamine, letting us know that what we are going to see is
in fact Dopamine.
Method
The task of understanding how dopaminergic cells contribute to the control of
movement may be effectively realized in animals with simpler nervous systems,
where the synaptic connections of identified neurons can be directly examined.
Due to its simplicity, the CNS from the snail Helisoma trivolvis can be used to study
the role of dopaminergic neurons in movement disorders.
In order to make these studies it is necessary to identify and localize the dopaminergic
neurons involved in control movement.
In these work we are going to use immunohistochemical and immunoflourecense
techniques to identify the dopaminergic neurons belonging to the pedal, buccal, cerebral
and abdominal ganglia.
These are the Procedures that are going to be made, each day as illustrated in the
Gantt graphic.
Annotated Bibliography
Murphy, D., Lukowiak, K., Stell, W. (1985). Peptidergic modulation
of patterned motor activity in identified,82, 7140-7144.
Peptidergic modulation of patterned motor activity in identified
neurons of Helisoma
(Phe-Met-Arg-Phe-NH2/small cardloactive peptide B/molluscan feeding/snail)
A. D. MURPHY*, KEN LUKOWIAK*, AND W. K. STELLt
*Department of Medical Physiology, Faculty of Medicine; and tDepartment of Anatomy/Faculty
of Medicine, University of Calgary, Calgary, Alberta, Canada
T2N 4N1
Communicated by Theodore H. Bullock, June 24, 1985
Abstract
The neuroaftive peptides SCPB (small cardioactive peptide B) and FMRFamide (Phe-Met-ArgPhe-NH2), both originally isolated from molluscs, have potent modulatory effects upon the
production of patterned motor activity in identified neurons (e.g., B5 and B19) in the buccal
ganglia of the snail Helisoma. Such patterned motor activity has previously been shown to
underlie feeding behavior. Micromolar concentrations of SCPB initiate patterned motor activity in
quiescent ganglia and increase the rate of activity in ganglia that are spontaneously active.
Micromolar concentrations of FMRFamide inhibit patterned motor activity in Helisoma buccal
ganglia, and 10 FLM FMRFamjde completely suppresses such activity. In addition, there are
both anti-SCPBand anti-FMRFamide immunoreactive neurons in Helisoma buccal ganglia. Our
results suggest that peptides may play a prominent role in the regulation of feeding behavior in
Helisoma.
During, M., Naegele, J., O’Malley, K. & Geller, A. (1994).
NIH-PA Science. Author Manuscript. Long-Term Behavioral Recovery in Parkinsonian Rats by
an HSV Vector Expressing Tyrosine Hydroxylase, 266(5189), 1399–1403.
Long-Term Behavioral Recovery in Parkinsonian Rats by an HSV
Vector Expressing Tyrosine Hydroxylase
Matthew J. During, Janice R. Naegele, Karen L. O’Malley, and Alfred I. Geller
M. J. During, Departments of Surgery and Medicine, Yale University School of Medicine, New
Haven, CT 06510, USA.J. R. Naegele, Department of Biology, Wesleyan University,
Middletown,
CT 06457, USA.K. L. O’Malley, Department of Anatomy and Neurobiology, Washington
University
School of Medicine, St. Louis, MO 63110, USA.A. I. Geller, Division of Endocrinology, Children’s
Hospital, and Program in Neuroscience, Harvard Medical School, Boston, MA 02115, USA.
Abstract
One therapeutic approach to treating Parkinson’s disease is to convert endogenous striatal cells
into levo-3, 4-dihydroxyphenylalanine (L-dopa)–producing cells. A defective herpes simplex
virus type 1 vector expressing human tyrosine hydroxylase was delivered into the partially
denervated striatum of 6-hydroxydopamine–lesioned rats, used as a model of Parkinson’s
disease. Efficient behavioral and biochemical recovery was maintained for 1 year after gene
transfer. Biochemical recovery included increases in both striatal tyrosine hydroxylase enzyme
activity and in extracellular dopamine concentrations. Persistence of human tyrosine
hydroxylase was revealed by expression of RNA and immunoreactivity.
Kiehn, L., Saleuddin, S., Lange, A. (2001).
Dopaminergic neurons in the brain and dopaminergic innervation. BMC Physiology,
1(9), 1-13. Retrieved from http://www.biomedcentral.com/1472-6793/1/9
Dopaminergic neurons in the brain and dopaminergic innervations of the albumen gland
in mated and virgin helisoma duryi (mollusca:pulmonata)
Lana Kiehn1, Saber Saleuddin*2 and Angela Lange3
Address: 1Department of Biology, York University, Toronto, Ontario, M3J1P3, Canada,
2Department of Biology, York University, Toronto,
Ontario, M3J1P3, Canada and 3Department of Zoology, University of Toronto at Mississauga,
Mississauga, Ontario, L5L1C6, Canada
E-mail: Lana Kiehn - lana@yorku.ca; Saber Saleuddin* - saber@yorku.ca; Angela Lange alange@credit.erin.utoronto.ca
*Corresponding author
Abstract
Dopamine was shown to stimulate the perivitelline fluid secretion by the albumen gland. Even
though the albumen gland has been shown to contain catecholaminergic fibers and its
innervation has been studied, the type of catecholamines, distribution of fibers and the precise
source of this neural innervation has not yet been deduced. This study was designed to address
these issues and examine the correlation between dopamine concentration and the sexual
status of snails. Dopaminergic neurons were found in all ganglia except the pleural and right
parietal, and their axons in all ganglia and major nerves of the brain. In the albumen gland
dopaminergic axons formed a nerve tract in the central region, and a uniform net in other areas.
Neuronal cell bodies were present in the vicinity of the axons. Dopamine was a major
catecholamine in the brain and the albumen gland. No significant difference in dopamine
quantity was found when the brain and the albumen gland of randomly mating, virgin and first
time mated snails were compared.Our results represent the first detailed studies regarding the
catecholamine innervation and quantitation of neurotransmitters in the albumen gland. In this
study we localized atecholaminergic neurons and axons in the albumen gland and the brain,
identified these neurons and axons as dopaminergic, reported monoamines present in the
albumen gland and the brain, and compared the dopamine content in the brain and the albumen
gland of randomly mating, virgin and first time mated snails.
Sun, M., Zhang, G., Kong, L., Holmes, C., Wang, Z., Zhang, W. & Alfred,G. (2003). Correction
of a Rat Model of Parkinson’s Disease by Coexpression. NIH-PA Author Manuscript, 14 (5),
415–424. doi:1089/104303403321467180
Correction of a Rat Model of Parkinson’s Disease by Coexpression
of Tyrosine Hydroxylase and Aromatic Amino Acid Decarboxylase
from a Helper Virus-Free Herpes Simplex Virus Type-1 Vctor
MEI SUN1, GUO-RONG ZHANG1, LINGXIN KONG1, COURTNEY HOLMES2, XIAODAN
WANG1, WEI ZHANG1, DAVID S. GOLDSTEIN2, and ALFRED I. GELLER1
1 Department of Neurology, West Roxbury VA Hospital/Harvard Medical School, West Roxbury,
MA 02132.
2 Clinical Neurocardiology Section, National Institute of Neurological Disorders and Stroke,
Bethesda, MD 20892.
Abstract
We previously reported long-term biochemical and behavioral correction of the 6hydroxydopamine (6-OHDA) rat model of Parkinson’s disease (PD) by expression of tyrosine
hydroxylase (TH) in the partially denervated striatum, using a herpes simplex virus type 1 (HSV1) vector. This study had a number of limitations, including the use of a helper virus packaging
system, limited long-term expression, and expression of only TH. To address these issues, we
developed a helper virus-free packaging system, a modified neurofilament gene promoter that
supports long-term expression in forebrain neurons, and a vector that coexpresses TH and
aromatic amino acid decarboxylase (AADC). Coexpression of TH and AADC supported highlevel (80%), behavioral correction of the 6-OHDA rat model of PD for 5 weeks. Biochemical
correction included increases in extracellular dopamine and DOPAC concentrations between 2
to 4 months after gene transfer. Histologic analyses demonstrated neuronal-specific
coexpression of TH and AADC at 4 days to 7 months after gene transfer, and cell counts
revealed 1000 to 10,000 TH positive cells per rat at 2 months after gene transfer. This improved
system efficiently corrects the rat model of PD.
Kelly, B., Hedlund, E., Ishuguro, H., Ishiguro, O., Isacson, D., Chlkaraishi K. & Feng, G.
(2006).
A TYROSINE HYDROXYLASE–YELLOW FLUORESCENT PROTEIN KNOCK-IN REPORTER
SYSTEM LABELING DOPAMINERGIC NEURONS REVEALS POTENTIAL REGULATORY
ROLE FOR THE FIRST INTRON OF THE RODENT TYROSINE HYDROXYLASE GENE. NIHPA
Neuroscience.
Author
Manuscript,
142(2),
343–354.
doi:10.1016/j.neuroscience.2006.06.032.
A TYROSINE HYDROXYLASE–YELLOW FLUORESCENT PROTEIN KNOCK-IN REPORTER
SYSTEM LABELING DOPAMINERGIC NEURONS REVEALS POTENTIAL REGULATORY
ROLE FOR THE FIRST INTRON OF THE RODENT TYROSINE HYDROXYLASE GENE
B. B. KELLYa, E. HEDLUNDc,d,e, C. KIMc,d, H. ISHIGUROf, O. ISACSONc,e, D. M.
CHIKARAISHIa, K.-S. KIMc,d, and G. FENGa,b,*
aDepartment of Neurobiology, Box 3209, Duke University Medical Center, Durham, NC 27710,
USA
bDepartment of Pathology, Duke University Medical Center, Durham, NC 27710, USA
cUdall Parkinson’s Disease Research Center of Excellence, McLean Hospital/Harvard Medical
School, MA
02478, USA
dMolecular Neurobiology Laboratory, McLean Hospital/Harvard Medical School, Belmont, MA
02478, USA
eNeuroregeneration Laboratory, McLean Hospital/Harvard Medical School, Belmont, MA 02478,
USA
fCarna Bioscience, KIBC 511, 5-5-2, Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047,
Hyogo, Japan
Abstract
Degeneration of the dopaminergic neurons of the substantia nigra is a hallmark of Parkinson’s
disease. To facilitate the study of the differentiation and maintenance of this population of
dopaminergic neurons both in vivo and in vitro, we generated a knock-in reporter line in which
the yellow fluorescent protein (YFP) replaced the first exon and the first intron of the tyrosine
hydroxylase (TH) gene in one allele by homologous recombination. Expression of YFP under
the direct control of the entire endogenous 5′ upstream region of the TH gene was predicted to
closely match expression of TH from the wild type allele, thus marking functional dopaminergic
neurons. We found that YFP was expressed in dopaminergic neurons differentiated in vitro from
the knockin mouse embryonic stem cell line and in dopaminergic brain regions in knock-in mice.
Surprisingly, however, YFP expression did not overlap completely with TH expression, and the
degree of overlap varied in different TH-expressing brain regions. Thus, the reporter gene did
not identify functional TH-expressing cells with complete accuracy. A DNaseI hypersensitivity
assay revealed a cluster of hypersensitivity sites in the first intron of the TH gene, which was
deleted by insertion of the reporter gene, suggesting that this region may contain cis-acting
regulatory sequences. Our results suggest that the first intron of the rodent TH gene may be
important for accurate expression of TH.
Heinz, A., Beck, A. (2008). The intricacies of dopamine neuron modulation. NIH-PA Biol
Psychiatry. Author Manuscript, 65(2), 101–102. doi:10.1016/j.biopsych.2008.11.003.
The intricacies of dopamine neuron modulation
Andreas Heinz1, Anthony A. Grace2, and Anne Beck1
1 Department of Psychiatry and Psychotherapy, Charité-University Medical Center Berlin, CCM
2 Departments of Neuroscience, Psychiatry and Psychology, University of Pittsburgh,
Pittsburgh,
PA USA
Abstract
The midbrain dopamine system has been traditionally associated with reward-related
phenomena; however, recent studies suggest a more generalized role for this transmitter
system. In this issue of Biological Psychiatry, Krebs, Schott and Düzel use imaging studies in
humans to provide evidence for a fascinating modulation of presumably dopaminergic midbrain
neurons, depending on personality traits of the individuals performing the tasks. The authors
suggest that the personality traits “reward dependence” and “novelty seeking” modulate
neuronal activation elicited by reward-predicting versus novel non-rewardassociated pictures in
the substantia nigra/ventral tegmental area (1). This finding may help to redefine
neurotransmitter correlates of partially heritable personality traits and thus help to explain how
two apparently independent personality traits (i.e. “novelty seeking” and “reward dependence”)
can both be associated with behaviourally relevant phasic activation of midbrain dopamine
neurons. In 1987, Cloninger suggested that “novelty seeking”, “reward” dependence” and “harm
avoidance” are independent and partially heritable personality factors, which are modulated by
dopamine, norepinephrine, and serotonin, respectively (2). Further studies partially confirmed
this hypothesis: “harm avoidance” was indeed associated with negative mood states such as
depression and anxiety, which are modulated by serotonin function in human and non-human
primates (3). However, animal experiments provided little proof for direct associations between
norepinephrine neurotransmission and “reward dependence” as a personality trait. Instead,
animal experiments suggested that activation of midbrain dopaminergic neurons can be elicited
by both novel and reward-predicting .
Ford, C., Phillips, P., Williams, J. (2009). The Time Course of Dopamine Transmission in the
Ventral Tegmental Area. NIH-PA J Neurosci. Author Manuscript, 29(42), 13344–13352.
doi:10.1523/JNEUROSCI.3546-09.2009.
The Time Course of Dopamine Transmission in the Ventral
Tegmental Area
Christopher P. Ford1, Paul E.M. Phillips2, and John T. Williams1,3
1Vollum Institute, Oregon Health & Science University L474, 3181 SW Sam Jackson Park
Road,
Portland, OR, 97239, USA
2Department of Psychiatry and Behavioral Sciences and Department of Pharmacology,
University
of Washington, Seattle, WA, 98195, USA
Abstract
Synaptic transmission mediated by G-protein coupled receptors (GPCR) is not generally
thought to be point-to-point. To determine the extent over which dopamine signals in the
midbrain, the present study examined the concentration and time course of dopamine that
underlies a D2-receptor inhibitory post-synaptic current (D2-IPSC) in the ventral tegmental area
(VTA). Extracellular dopamine was measured electrochemically while simultaneously recording
D2-IPSCs. The presence of dopamine was brief relative to the IPSC, suggesting that G-protein
dependent potassium channel activation determined the IPSC time course. The activation
kinetics of D2 receptor-dependent potassium current was studied using outside-out patch
recordings with rapid application of dopamine. Dopamine applied at a minimum concentration of
10 μM for a maximum of 100 ms mimicked the IPSC. Higher concentrations applied for as little
as 5 ms did not change the kinetics of the current. The results indicate that both the intrinsic
kinetics of G-protein coupled receptor signaling and a rapidly rising high concentration of
dopamine determine the time course of the IPSC. Thus dopamine transmission in the midbrain
is more localized then previously proposed.
Goldstein, D., Holmes, C., Bentho, O., Sato, T., (2008).
BIOMARKERS TO DETECT CENTRAL DOPAMINE DEFICIENCY AND DISTINGUISH
PARKINSON DISEASE FROM MULTIPLE SYSTEM ATROPHY. NIH-PA Parkinsonism Related
Disord. Author Manuscript, 14(8), 600–607. doi:10.1016/j.parkreldis.2008.01.010.
BIOMARKERS TO DETECT CENTRAL DOPAMINE DEFICIENCY AND DISTINGUISH
PARKINSON DISEASE FROM MULTIPLE SYSTEM ATROPHY
David S. Goldstein, MD PhD1, Courtney Holmes, CMT1, Oladi Bentho1, Takuya Sato1, Jeffrey
Moak, MD2, Yehonatan Sharabi, MD1, Richard Imrich, MD PhD1, Shielah Conant3, and Basil
A. Eldadah, MD PhD
1Clinical Neurocardiology Section, National Institute of Neurological Disorders and Stroke,
National
Institutes of Health, Bethesda, MD 20892
2PET Department, Clinical Center, National Institutes of Health, Bethesda, MD 20892
3Geriatrics and Clinical Gerontology Program, National Institute on Aging, National Institutes of
Health,
Bethesda, MD 20892
Abstract
Biomarkers are increasingly important to diagnose and test treatments of neurodegenerative
diseases such as Parkinson disease (PD). This study compared neuroimaging, neurochemical,
and olfactory potential biomarkers to detect central dopamine (DA) deficiency and distinguish
PD from multiple system atrophy (MSA). In 77 PD, 57 MSA, and 87 control subjects,
radioactivity concentrations in the putamen (PUT), caudate (CAU), occipital cortex (OCC), and
substantia nigra (SN) were measured 2 hours after 6-[18F]fluorodopa injection, septal
myocardial radioactivity measured 8 minutes after 6-[18F] fluorodopamine injection, CSF and
plasma catechols assayed, or olfaction tested (University of Pennsylvania Smell Identification
Test (UPSIT)). Receiver operating characteristic curves were constructed, showing test
sensitivities at given specificities. PUT:OCC, CAU:OCC, and SN:OCC ratios of 6[18F]fluorodopa-derived radioactivity were similarly low in PD and MSA (p<0.0001, p<0.0001,
p=0.003 compared to controls), as were CSF dihydroxyphenylacetic acid (DOPAC) and DOPA
concentrations (p<0.0001 each). PUT:SN and PUT:CAU ratios were lower in PD than in MSA
(p=0.004; p=0.005). CSF DOPAC correlated positively with PUT:OCC ratios (r=0.61, p<0.0001).
Myocardial 6-[18F]fluorodopamine-derived radioactivity distinguished PD from MSA (83%
sensitivity at 80% specificity, 100% sensitivity among patients with neurogenic orthostatic
hypotension (NOH)). Only PD patients were anosmic; only MSA patients had normal olfaction
(61% sensitivity at 80% specificity). PD and MSA feature low PUT:OCC ratios of 6[18F]fluorodopa-derived radioactivity and low CSF DOPAC and DOPA concentrations, crossvalidating the neuroimaging and neurochemical approaches but not distinguishing the diseases.
Manta, S., Dong J., Debonnel, G., Blier, P. (2009).
Enhancement of the function of rat serotonin and norepinephrine neurons by sustained vagus
nerve stimulation. J Psychiatry Neurosciense, 34(4), 272-80.
Enhancement of the function of rat serotonin
and norepinephrine neurons by sustained
vagus nerve stimulation
Stella Manta, MSc; Jianming Dong, MD; Guy Debonnel, MD; Pierre Blier, MD, PhD
Manta, Blier — Institute of Mental Health Research, University of Ottawa, Ottawa, Ont.; Dong,
Debonnel, Blier — Department
of Psychiatry McGill University, Montréal Que.
Abstract
Vagus nerve stimulation (VNS) is a recent intervention for treatment-resistant depression.
Electrophysiological recordings in the rat brain showed that VNS increases the firing rate of
norepinephrine (NE) neurons after 1 day of stimulation and that of serotonin (5-HT) neurons
after 14 days. This study was conducted to further characterize these effects. We implanted rats
with a VNS electrode and stimulator. We used the selective noradrenergic toxin DSP-4 to lesion
NE neurons of the locus coeruleus. We recorded dorsal raphe 5-HT neurons under chloral
hydrate anesthesia. We recorded hippocampus CA3 pyramidal neurons using 5-barreled
iontophoretic pipettes. Analysis of a previously published data set revealed that VNS increased
not only the spontaneous firing rates of NE neurons, but also the percentage of neurons firing in
bursts. The enhancement of the 5-HT neuron firing rate by VNS was abolished by lesioning NE
neurons. We found that VNS increased the degree of activation of postsynaptic α1adrenoceptors on 5-HT neurons, probably through an increased release of endogenous NE.
The tonic activation of postsynaptic 5-HT1A receptors in the hippocampus was enhanced after
14 days of VNS, as with other antidepressant treatments. Our study limitations include the fact
that we turned off the stimulator during the electrophysiological recordings, which likely
decreased the vagal tone to the brain. Also, we obtained the data while the animals were under
anesthesia, therefore studies need to be carried out in unanesthetized rats to ascertain whether
the anesthetic agent influenced the changes observed between control rats and those treated
with VNS. Vagus nerve stimulation initially increases the firing activity and pattern of NE
neurons and subsequently those of 5-HT neurons, presumably as a cascade effect via α1postsynaptic adrenoceptors. To date, VNS appears to be a unique antidepressant treatment
increasing 5-HT transmission and enhancing the firing activity of NE neurons. These effects
could contribute to the effectiveness of VNS in treatment-resistant depression.
Matos, L., Trufelli, C., Matos, M., Pinhal, A. (2010). Immunohistochemistry as an Important Tool
in Biomarkers. Biomarker Insights, 2010(5), 9-20. Retrieved from http://www.l a-press.com
Immunohistochemistry as an Important Tool in
Biomarkers Detection and Clinical Practice
Leandro Luongo de Matos, Damila Cristina Trufelli, Maria Graciela Luongo de Matos and Maria
Aparecida da Silva Pinhal
Biochemistry Department, Faculdade de Medicina do ABC, Santo André, SP, Brazil.
Abstract
The immunohistochemistry technique is used in the search for cell or tissue antigens that range
from amino acids and proteins to infectious agents and specific cellular populations. The
technique comprises two phases: (1) slides preparation and stages involved for the reaction; (2)
interpretation and quantification of the obtained expression. Immunohistochemistry is an
important tool for scientific research and also a complementary technique for the elucidation of
differential diagnoses which are not determinable by conventional analysis with hematoxylin and
eosin. In the last couple of decades there has been an exponential increase in publications on
immunohistochemistry and immunocytochemistry techniques. This review covers the
immunohistochemistry technique; its history, applications, importance, limitations, difficulties,
problems and some aspects related to results interpretation and quantification. Future
developments on the immunohistochemistry technique and its expression quantification should
not be disseminated in two languages—that of the pathologist and another of clinician or
surgeon. The scientific, diagnostic and prognostic applications of this methodology must be
explored in a bid to benefit of patient. In order to achieve this goal collaboration and pooling of
knowledge from both of these valuable medical areas is vital.
References:
[1] Katz PS, Harris-Warrick RM. The evolution of neuronal circuits underlying
species-specific behavior. Curr Opin Neurobiol 9(5): 628-633, 1999.
[2] Miller MW, Alevizos A, Cropper EC, Vilim FS, Karagogeos D,
Kupfermannn I, Weiss KR. Localization of myomodulin-like immunoreactivity in
the central nervous system and peripheral tissues of Aplysia californica. J Comp
Neurol 314: 627-644, 1991.
During,
M.,
Naegele,
J.,
O’Malley,
K.
&
Geller,
A.
(1994).
NIH-PA Science. Author Manuscript. Long-Term Behavioral Recovery in
Parkinsonian Rats by an HSV Vector Expressing Tyrosine Hydroxylase, 266(5189),
1399–1403.
Ford, C., Phillips, P., Williams, J. (2009). The Time Course of Dopamine
Transmission in the Ventral Tegmental Area. NIH-PA J Neurosci. Author Manuscript,
29(42), 13344–13352. doi:10.1523/JNEUROSCI.3546-09.2009.
Goldstein, D., Holmes, C., Bentho, O., Sato, T., (2008).
BIOMARKERS TO DETECT CENTRAL DOPAMINE DEFICIENCY AND
DISTINGUISH PARKINSON DISEASE FROM MULTIPLE SYSTEM ATROPHY.
NIH-PA Parkinsonism Related Disord. Author Manuscript, 14(8), 600–607.
doi:10.1016/j.parkreldis.2008.01.010.
Heinz, A., Beck, A. (2008). The intricacies of dopamine neuron modulation. NIH-PA
Biol
Psychiatry.
Author
Manuscript,
65(2),
101–102.
doi:10.1016/j.biopsych.2008.11.003.
During,
NIH-PA
M.,
Naegele,
Science. Author
J.,
O’Malley,
K.
&
Geller,
Manuscript. Long-Term Behavioral
A.
(1994).
Recovery in
Parkinsonian Rats by an HSV Vector Expressing Tyrosine Hydroxylase, 266(5189),
1399–1403.
Kelly, B., Hedlund, E., Ishuguro, H., Ishiguro, O., Isacson, D., Chlkaraishi K. &
Feng, G. (2006).A TYROSINE HYDROXYLASE–YELLOW FLUORESCENT
PROTEIN KNOCK-IN REPORTER SYSTEM LABELING DOPAMINERGIC
NEURONS REVEALS POTENTIAL REGULATORY ROLE FOR THE FIRST
INTRON OF THE RODENT TYROSINE HYDROXYLASE GENE. NIH- PA
Neuroscience.
Author
Manuscript,
142(2),
343–354.
doi:10.1016/j.neuroscience.2006.06.032.
Matos, L., Trufelli, C., Matos, M., Pinhal, A. (2010). Immunohistochemistry as an
Important Tool in Biomarkers. Biomarker Insights, 2010(5), 9-20.Retrieved from
http://www.l a-press.com
Manta,
S.,
Dong
J.,
Debonnel,
G.,
Blier,
P.
(2009).
Enhancement of the function of rat serotonin and norepinephrine neurons by
sustained vagus nerve stimulation. J Psychiatry Neurosciense, 34(4), 272-80.
Murphy, D., Lukowiak, K., Stell, W. (1985).
of patterned motor activity in identified,82, 7140-7144.
Peptidergic
modulation
Sun, M., Zhang, G., Kong, L., Holmes, C., Wang, Z., Zhang, W. & Alfred,G. (2003).
Correction of a Rat Model of Parkinson’s Disease by Coexpression. NIH-PA Author
Manuscript, 14 (5), 415–424. doi:1089/104303403321467180