» Dr. Amaicha Depino

Research areas

Study of the physiological basis of autism

 

Objectives:

The main objective of our group is to understand the molecular and cellular mechanisms underlying the development of behaviors related to autism. We used in ourstudies animal models of disease and focus on analyzing the contribution of inflammation in the development of behavioral alterations.

Our working hypothesis is that perinatal inflammation contributes to behaviors related to autism. Our work is thus aimed at elucidating this contribution and the molecular and cellular mechanisms by which this happens.

Background:

The term autism is used generally to refer to a subset of diseases within the Pervasive Developmental Disorders (PDD). Autism is a severe disorder of neural development characterized by a sustained impairment in social interaction and communication, and by stereotyped or restrictive behavioral patterns. Symptoms typically begin in childhood,and the syndrome manifests itself completely around 4 years of age. According to recent epidemiological studies of these diseases, they affect between 2 and 6 of every 1000 children, depending on the country.

Although there is consensus about the existence of a genetic component, autism shows high genetic heterogeneity suggesting the interaction between a genetic predispositionand an environmental factor. Among these factors, maternal viral infection was cited as the main environmental cause, but has been poorly studied. In this vein, some studies have shown the presence of activated glia, neuroinflammation and cytokine expressionin some brain regions (cortex, amygdala, hippocampus and cerebellum) of patients withautism.

Our Research:

To study the mechanisms by which inflammatory processes can affect the developing brain and contribute to the symptoms of autism we use animal models. On one hand,we used a mouse model of autism: prenatal treatment of mice with sodium valproate (VPA). It thas been described a fetal valproate syndrome in humans, showing symptoms similar to autism. In mice we found that this treatment reduces social interaction in adult animals, modeling the main symptom of autism. We are evaluating this model the presence of inflammatory processes and their role in the development ofbehavioral disorders.

On the other hand, we observed that over expression of transforming growth factor beta(TGF-beta1) in the postnatal hippocampus results in several autism-related behaviors(decreased social interaction, increased repetitive behaviors, and increased behavior related to depression). We seek to understand how this factor alters the behavior and study whether TGF-beta1 is involved in pharmacological and genetic models of autism.

We hope our work contributes to a better understanding of the disease and the eventualdevelopment of treatments.

Relevant Publications:

Graciarena M., Roca V. Mathiey P., Depino A.M., Pitossi F.J. “Differential vulnerability of adult neurogenesis by adult and prenatal inflammation: Role of TGF-beta1”, Brain, Behavior and Immunity. En prensa. Publicado on-line el 31 de mayo de 2013.

 Depino A.M.*, Lucchina L., Pitossi F. ¨Early and adult hippocampal TGF-b1 overexpression have opposite effects on behavior¨. Brain, Behavior and Immunity 25 (8): 1582-91 (2011). (*autor corresponsal).
Alvarez MJ, Depino AM, Podhajcer OL and Pitossi FJ. “Bias in estimations of DNA content by competitive polymerase chain reaction¨. Analytical Biochemistry Vol. 287, No. 1, 87-94 (2000).
Alonso M, Vianna MRM, Depino AM, Mello e Souza T, Pereira P, Szapiro G, Viola H, Pitossi F, Izquierdo I and Medina JH. ¨Role of hippocampal BDNF during short and long-term memory formation¨. Hippocampus 12(4):551-560 (2002).
Depino AM, Earl C, Besedovsky H, del Rey A, Pitossi F and Oertel WH. ¨Microglial activation with atypical pro-inflammatory cytokine expression in a rat model of Parkinson´s disease¨. European Journal of Neuroscience 18(10):2731-2742 (2003).
Depino AM*, Alonso M, Ferrari C, del Rey A, Anthony D, Besedovsky H, Medina JH and Pitossi F. “Learning modulation by endogenous hippocampal IL-1: blockade of endogenous IL-1 facilitates memory formation¨. Hippocampus 14 (4): 526-535 (2004) (*autor corresponsal).
Ferrari CC, Depino AM, Prada F, Muraro N, Campbell S, Podhajcer O, Perry VH, Anthony DC, Pitossi FJ. “Reversible demyelination, blood-brain barrier breakdown, and pronounced neutrophil recruitment induced by chronic IL-1 expression in the brain”. American Journal of Pathology 165(5):1827-37 (2004).
Depino A, Ferrari C, Pott Godoy MC, Tarelli R, Pitossi FJ. “Differential effects of interleukin-1beta on neurotoxicity, cytokine induction and glial reaction in specific brain regions”. Journal of Neuroimmunology 168 (1-2): 96-110 (2005).
Depino AM*. “Maternal infection and the offspring brain”. The Journal of Neuroscience 26 (30): 7777-8 (2006). (*autor corresponsal). Art de revisión.
Depino AM, Gross C. “Simultaneous assessment of autonomic function and anxiety-related behavior in BALB/c and C57BL/6 mice”. Behavioural Brain Research 177: 154-160 (2007).
Depino AM, Tsetsenis T, Gross C. ¨GABA homeostasis contributes to the developmental programming of anxiety-related behavior¨. Brain Research 1210: 189-99 (2008).
Mathieu P.#, Battista D.#, Depino A., Roca V., Graciarena M., Pitossi F. “The more you have, the less you get: the functional role of inflammation on neuronal differentiation of endogenous and transplanted neural stem cells in the adult brain¨. Journal of Neurochemistry 112: 1368-1385 (2010). Art de revisión. # estos autores contribuyeron de forma equivalente.
Lucchina L., Carola V., Pitossi F., Depino A.M.* “Evaluating the interaction between postnatal inflammation and maternal care in the programming of adult anxiety and depression related behaviors” Behavioural Brain Research 213 (1): 56-65 (2010). (* autor corresponsal).
Graciarena M., Depino A.M., Pitossi F. “Prenatal inflammation impairs adult neurogenesis and object recognition memory through TGF-β1 downregulation” Brain, Behavior and Immunity 24 (8): 1301-9 (2010).
Chertoff M., Di Paolo N., Schoeneberg A., Depino A., Ferrari C., Wurst W., Pfizenmaier K., Eisel U., Pitossi F. “Neuroprotective and neurodegenerative effects of the chronic expression of Tumor Necrosis Factor alpha in the nigrostriatal dopaminergic circuit of adult mice” Experimental Neurology 227 (2): 237-51 (2011).

Book Articles:

Pitossi FJ, Depino A y Di Paolo N. Capíttulo 56. Cytokines in the central nervoussystem. In Molecular Immunopathology: New Frontiers in Medicine. A link betweenmedical research and clinical practice. Gabriel Adrian Rabinovich (Editor). ISBN:950-06-1868-0. 614 páginas. Editorial Medica Panamericana, 2004, Madrid
Amaicha M. Depino. “Pro-inflammatory Cytokines in Learning and Memory”. ISBN:978-1-61668-626-0. Nova Publishers, in press, EEUU. Nota: Note: This book is theindependent publication of the chapter that follows.
Amaicha M. Depino. Chapter 3. Pro-inflammatory Cytokines in Learning and Memory.In: Learning and Memory Developments and Intellectual Disabilities. ISBN:978-1-60876-397-9. Nova Publishers, in press, EEUU..
Amaicha Depino, Patricia Mathieu, Carina Ferrari y Fernando Pitossi. Capítulo 12.Immune Response in neurodegenerative diseases. In: Clinical NeuroimmunologyEditorial Médica Panamericana, in press.

Current research grants:

  • Identification of the physiological bases of the development of autism-related behavior in mice, PICT-2010-1334. IFIByNE, UBA-CONICET. Principal Investigator: Amaicha Mara Depino
  • Role of the cytokine TGF-beta1 in the development and manifestation of autism.
    PIP 2010-2012 IU No. 11420090100217. IFIBYNE.
    Researcher: Mara Amaicha Depino.
  • Study of the effects of prenatal inflammation on a mouse model of autism.
    GEF 2010-2012 UBACyT No. 20020090200203.
    Researcher: Mara Amaicha Depino.

Awards:

  • 2011 John Kendrew Young Scientist Award
    This award recognizes excellence in scientific and academic achievements after leavingthe European Molecular Biology Laboratory. It will be presented on June 10, 2011 at EMBL, Heidelberg, Germany, by Nobel laureate Sydney Brenner.

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Group members

INVESTIGADOR A CARGO

Dra. Amaicha Depino

Dra. Amaicha Depino

Investigadora Independiente

BECARIOS


Lic. Nadia Kazlauskas

Lic. Nadia Kazlauskas
Becaria de Doctorado

Lic. Marcos Campolongo

Lic. Marcos Campolongo
Becario de Doctorado

Lic. Cecilia Zappala

Lic. Cecilia Zappala
Becaria de Doctorado

Lic. Araceli Seiffe

Lic. Araceli Seiffe
Becaria de Doctorado

Ex Integrantes

Lic. Luciana Lucchina

Lic. Luciana Lucchina