LABORATORY OF CELL BIOLOGY

STAFF

M. Mónica Brauer, PhD – Head of Laboratory. (brauer@iibce.edu.uy)

M. Cecilia Scorza, PhD – Associate Researcher. (scorza@iibce.edu.uy)

Analía Richeri, MSc – PhD Student (aricheri@iibce.edu.uy)

Jessika Urbanavicius - Fellow (jessikau@iibce.edu.uy)

Paola Bianchimano – Fellow (pbianchi@iibce.edu.uy)

Ma Noel Meikle - Fellow (manomei@iibce.edu.uy)

Ximena López - Honorary Researcher (ximelh@montevideo.com.uy)

RESEARCH LINES

1. Cellular and molecular mechanisms underlying plasticity in uterine nerves

(M.M. Brauer, PhD)

1.1 Aims

The nature of target-derived signals regulating sex hormone- and pregnancy-induced remodeling of uterine nerves is analyzed using a combination of immunohistochemical, biochemical and molecular methods. Studies are focused on the role of soluble neurotrophic factors (i.e. NGF) and their neuronal receptors. Work is in progress to elucidate the contribution of negative signals provided by the uterine extracellular matrix and members of the semaphorin family to these events.

1.2 Publications

Brauer M.M., Llodrá J., Scorza C., Chávez R., Burnstock G., Thrasivoulou C., Cowen T. Diferential effects of prepubertal chronic oestrogen treatment on the synthesis of noradrenaline in myometrial and perivascular sympathetic nerves. International Journal of Developmental Neuroscience 17: 295-303.

Brauer MM, Chávez-Genaro R., Llodrá J., Richeri A., Scorza MC. Effects of chronic oestrogen treatment are not selective for uterine sympathetic nerves: a transplantation study. Journal of Anatomy 196, 347-355.

Brauer MM, Shockley KP, Chávez R., Richeri A, Cowen T, Crutcher KA, The role of NGF in pregnancy-induced degeneration and regeneration of sympathetic nerves in the guinea pig uterus. Journal of the Autonomic Nervous System 79, 19-27.

Chávez-Genaro, K. Crutcher , L. Viettro, A. Richeri, N. Coirolo , G. Burnstock, T. Cowen, M.M. Brauer. Differential effects of oestrogen on developing and mature uterine sympathetic nerves. Cell and Tissue Research 308: 61-73.

Richeri A, Viettro L, Chávez-Genaro R, Burnstock G, Cowen T, Brauer MM. Effects of infantile/prepubertal chronic oestrogen treatment and chemical sympathetctomy with guanethidine on developing cholinergic nerves of the rat uterus. J. Histochem. Cytochem 50: 839-850.

Brauer MM, Chávez-Genaro R, Richeri A, Viettro L., Frias AI, Burnstock G, Cowen T. The oestrogenized rat myometrium inhibits organotypic sympathetic reinneravtion. Autonom. Neurosci: Basic and Clinic 101: 13-22.

Chalar C, Richeri A., Viettro L, Chávez-Genaro R, Bianchimano P, Mármol NM, Crutcher K, Burnstock G, Cowen T, Brauer MM, Plasticity in rat uterine sensory nerves: the role of NGF and trkA. Cell and Tissue Research 314: 191-205.

Richeri A, Bianchimano P, Marmol NM, Viettro L, Cowen T, Brauer MM. Plasticity in rat uterine sympathetic nerves: the role of TrkA and p75 nerve growth factor receptors. J Anat. 207(2):125-34.

Bianchimano P, Frías AI, Richeri A, Brauer MM. Effects of dexamethasone on estrogen- and pregnancy-induced plasticity in rat uterine sympathetic nerves. Cell Tissue Res. Sep 28; [Epub ahead of print].

2.1.- Study of the neurobiological basis (brain pathways, neurochemical systems and brain receptors) of different drugs used for the treatment of neuropsychiatry diseases like anxiety, depression, schizophrenia or addiction.

(C. Scorza, PhD)

2.2.- Study of mechanism of action of drugs abuse (amphetamines derivatives, and coca-paste).

(C. Scorza, PhD)

For both items, we used basically behavioral approaches, such as animal models of anxiety (elevated plus-maze), animal models to detect antidepressant profile of new compounds (forced swim test or tail suspension), models to quantify changes in the general motor activity (open field). Also, we usually include neurochemical methods to measure changes in brain tissue levels of neurotransmitters (dopamine, serotonine and noradrenaline) or in vivo intracerebral microdialysis technique to study the effect of drugs in the release of some of the monoaminergic neurotransmitters mentioned above.
We believe that an appropriate knowledge of the neurobiology of action of the compounds used nowadays in the therapy of psychiatric disorders or the drugs abuse mechanism of action may contribute to develop more selective and effective treatments for neuropsychiatric diseases and addiction.

2.2 Publications

Acuña, C. Scorza, M. Reyes-Parada- B. K. Cassels, J. Huidobro-Toro. ALEPH-2, a suspected anxiolytic and putative hallucinogen phenylisopropylamine derivative is a serotonergic agonist acting on 5-HT2A and 5-HT2C receptors. Life Science.

Hervas, T. Vilaró, L. Romero, C. Scorza, G. Mengod, F. Artigas. Desensitization of 5-HT1A autoreceptors by low chronic fluoxetine dose. Effect of the concurrent administration of WAY-100635. Neuropsychopharmacology, 24: 11-20.

M. Gobbi, M. Moia, L. Pirona, Miguel Reyes-Parada, Cecilia Scorza, and T. Mennini. P Methyl-thio-amphetamine and 1-(m-chlorophenyl)-piperazine, two non-neurotoxic 5-HT releasers in vivo, differ from neurotoxic amphetamine derivatives in their mode of action at 5-HT nerve endings in vitro. Journal of Neurochemistry 82: 1435-1443.

Bortolozzi A, Diaz-Mataix L, Scorza MC, Celada P, Artigas F. The activation of 5-HT receptors in prefrontal cortex enhances dopaminergic activity. J Neurochem. 95(6):1597-607.

Diaz-Mataix L, Scorza MC, Bortolozzi A, Toth M, Celada P, Artigas F. Involvement of 5-HT1A receptors in prefrontal cortex in the modulation of dopaminergic activity: role in atypical antipsychotic action. J Neurosci. 25(47):10831-43.

Bortolozzi A, Diaz-Mataix L, Scorza MC, Celada P, Artigas F. The activation of 5-HT receptors in prefrontal cortex enhances dopaminergic activity. J Neurochem. 95(6):1597-1607.

2007-2009 'Target regulation of uterine innervation'
Funded by NIH, FIRCA.
PI: Dra. M.Mónica Brauer (Uruguay, I.I.B.C.E.); ,Prof. Keith Crutcher (USA, University of Cincinnati).

2007-2009 ' Mechanism of action of coca paste and other isolated alcaloids on the central nervous system: a pre-clinical study.'
Funded by: PDT 76/26 (Programa de Desarrollo Tecnológico). Area: Health.
PI: Dra. Cecilia Scorza (Uruguay, I.I.B.C.E.).

2007-2009 ' Study of the neurobiological basis of depression: role of melanin concentrating hormone '
Funded by: PDT (Programa de Desarrollo Tecnológico). Area: Health.
PI: Dr. Pablo Torterolo, Faculty of Medicine, UdelaR;
Dra. Cecilia Scorza, I.I.B.C.E.

2006-2007 Cooperative project Uruguay-Brazil on Molecular Genetics in forensic psychiatry:
'Suicides in Bello Horizonte and Montevideo: molecular study and psychological autopsy'
Funded by: PDT- DICyT (Uruguay) and CNPq (Brazil).
PI: Dra. Cecilia Scorza, I.I.B.C.E.

2005-2006 'Study of the neurobiological basis of antipsychotic action'.
Funded by DICyT-MEC, Fondo Clemente Estable.
PI: Dra. Cecilia Scorza.

2005-2006 'Role of semaphorins in estrogen-induced uterine sympathetic denervation'.
Funded by DICyT-MEC, Fondo Clemente Estable.
PI: Dra. M. Mónica Brauer.

1999–2002 'Molecular mechanisms underlying plasticity in uterine sympathetic nerves'.
Funded by: The Wellcome Trust (UK)
PI: Dra. M. Mónica Brauer.

TEACHING ACTIVITIES

Training of postgraduate students:

Master Students
- MD, Gustavo Ferriero (PROINBIO).

PhD Students
- MSc. Analía Richeri . PEDECIBA (Basic Science Development Program) Cell and Molecular Biology.

Organization of Postgraduate Courses
- Axon guidance (2003).
-VI, VII, VIII Sessions of the SCHOOL OF NEUROSCIENCE (Escuela Latinoamericana de Neurociencia)
Supported by:
PEDECIBA (Basic Science Development Program)
IBRO (International Brain Research Organization)
ISN (International Society of Neurochemistry)
IPICS (International Program in the Chemical Sciences)

CONTACT

Instituto de Investigaciones Bilologicas Clemente Estable. Laboratory of Cell Biology
Avenida Italia 3318 C.P 11600 Montevideo – Uruguay
Phone: (+598 2) 487 1616 ext 115-116 Fax: (+598 2) 487 5548

e-mail: brauer@iibce.edu.uy; scorza@iibce.edu.uy