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Leonardo H. Tonelli, PhD

Academic Title:

Associate Professor

Primary Appointment:

Psychiatry

Location:

MSTF, 934E

Phone (Primary):

(410) 706-2325

Fax:

(410) 706-0571

Education and Training

I received my PhD degree in Neurobiology from Universidad Nacional de Cordoba, Argentina, November 1997. I received postdoctoral training at the National Institute of Mental Health (NIMH) first at the Section on Pharmacology and then in the Section of Neuroendocrinology, Immunology and Behavior. I Joined the Department of Psychiatry in 2005 as an Assistant Professor where I established an independent research program. I was appointed a Health Research Scientist at the Baltimore VA in 2011 and was promoted to the rank of Associate Professor in 2012. I was awarded the position of invited faculty at the Maryland Psychiatric Research Center in 2013.

Biosketch

I am a psychoneuroimmunologist with background in neuroendocrinology, behavioral neuroscience and molecular biology. I also have experience in clinical research and postmortem human studies in mental health. My research program is focused on identifying novel mechanisms by which inflammatory processes affect CNS function and contribute to mental disorders. My current research is focused into the following 3 main areas: 1) Role of T cell mediated immunity on stress responsiveness and emotional behavior, which is done in mouse models 2) Neuroimmunological consequences of maternal immune activation which is carried out in rats and mice 3) Cellular and molecular studies of peripheral immunity in mental health patients. Few of our current findings include the identification of CD8+ T cells as key regulators of inflammatory and behavioral responses to repeated traumatic stress exposure and the immunoregulatory and immunosuppressive functions of kynurenic acid. My closest collaborators are Dr. Todd Gould, an expert on mouse models of mood and anxiety phenotypes, Dr. Achsah Keegan, a renowned immunologist and expert in T cell biology, Dr. Robert Schwarcz, a world expert in kynurenic acid and Dr. Clark, who has been trained in psychoneuroimmunolgy in my laboratory.

 

Highlighted Publications

-Immune status influences fear and anxiety responses in mice after acute stress exposure. Clark SM, Sand J, Francis TC, Nagaraju A, Michael KC, Keegan AD, Kusnecov A, Gould TD, Tonelli LH. Brain Behav Immun (2014) 38:192-201. PMID: 24524915

-Dissociation between sickness behavior and emotionality during lipopolysaccharide challenge in lymphocyte deficient Rag2-/- mice. Clark SM, Michael KC, Klaus J, Mert A, Romano-Verthelyi A, Sand J, Tonelli LH. Behav Brain Res. (2014) 278C:74-82. PMID: 25257108

-Expansion of brain T cells in homeostatic conditions in lymphopenic Rag2-/- mice. Song C, Nicholson JD, Clark SM, Li X, Keegan AD, Tonelli LH. Brain Behav Immun. (2016) 30062-9. PMID: 27013354

-CD4(+) T cells confer anxiolytic and antidepressant-like effects, but enhance fear memory processes in Rag2-/- mice. Clark SM, Soroka JA, Song C, Li X, Tonelli LH. Stress. (2016) 19(3):303-11. PMID: 27295202

-Reduced Kynurenine Pathway Metabolism and Cytokine Expression in the Prefrontal Cortex of Depressed Individuals. Clark S, Pocivavsek A, Nicholson JD, Notarangelo F, Langenberg P, McMahon RP, Kleinman JE, Hyde TM, Stiller J, Postolache TT, Schwarcz R, Tonelli LH. Journal of Psychiatry and Neuroscience (2016) 41(4)150226. PMID: 2707035

Additional Publication Citations

-Intranasal immune challenge induces sex-dependent depressive-like behavior and cytokine expression in the brain. Tonelli LH, Holmes A, Postolache TT. Neuropsychopharmacology (2008) 33(5):1038-48. PMID: 17593929

-Allergic rhinitis induces anxiety-like behavior and altered social interaction in rodents. Tonelli LH, Katz M, Kovacsics CE, Gould TD, Joppy B, Hoshino A, Hoffman G, Komarow H, Postolache TT. Brain Behav Immun (2009) (6):784-93. PMID: 19268702

-Glucocorticoid Receptor Dimerization Is Required for Proper Recovery of LPS-induced Inflammation, Sickness Behavior and Metabolism in Mice. Silverman MN, Mukhopadhyay P, Belyavskaya E, Tonelli LH, Revenis BD, Doran JH, Ballard BE, Tam J, Pacher P, Sternberg, EM. Molecular Psychiatry. (2012) 18(9):1006-17. PMID: 23089634

-Pollen-specific immunoglobulin E positivity is associated with worsening of depression scores in bipolar disorder patients during high pollen season. Manalai P, Hamilton RG, Langenberg P, Kosisky SE, Lapidus M, Sleemi A, Scrandis D, Cabassa JA, Rogers CA, Regenold WT, Dickerson F, Vittone BJ, Guzman A, Balis T, Tonelli LH, Postolache TT. Bipolar Disord. (2012) Feb;14(1):90-8. PMID: 22329476

-Expression and regulation in the brain of the chemokine CCL27 gene locus. Gunsolly C, Nicholson JD, Listwak SJ, Ledee D, Zelenka P, Verthelyi D, Chapoval S, Keegan A, Tonelli LH. J Neuroimmunol. (2010) 225(1-2):82-90 PMID: 20605223

-Elevated cytokine expression in the orbitofrontal cortex of victims of suicide. Tonelli LH, Stiller J, Rujescu D, Giegling I, Schneider B, Maurer K, Schnabel A, Moller H-J, Chen HH, Postolache TT. Acta Psychiatr Scand (2008) 117(3):198-206. PMID: 18081924

-Toxoplasma gondii antibody titers and history of suicide attempts in patients with recurrent mood disorders. Arling TA, Yolken RH, Lapidus M, Langenberg P, Dickerson FB, Zimmerman SA, Balis T, Cabassa JA, Scrandis DA, Tonelli LH, Postolache TT. J Nerv Ment Dis. (2009) 197(12):905-8. PMID: 20010026

-Acute Stress Promotes Aggressive-Like Behavior in Rats Made Allergic to Tree Pollen. Tonelli LH, Hoshino A, Katz M, Postolache TT. Int J Child Health Hum Dev. 2008;1(3):305-312. PMID: 20622938

-Tumor necrosis factor alpha, interleukin-1 beta, interleukin-6 and major histocompatibility complex molecules in the normal brain and after peripheral immune challenge. Tonelli LH, Postolache TT. Neurol Res. (2005) 27(7):679-84. PMID: 16197804

-Differential induction of interleukin-I beta mRNA in the brain parenchyma of Lewis and Fischer rats after peripheral injection of lipopolysaccharides. Tonelli LH, Maeda S, Rapp KL, Sternberg EM. J Neuroimmunol. (2003) 140(1-2):126-36. PMID: 12864980

-Differential expression of class I MHC mRNA in the hypothalamus of Lewis and Fischer rats. Puchowicz M, Tonelli LH, Sternberg EM. J Neuroimmunol. (2003) 134(1-2):35-43. PMID: 12507770

 

Complete list of publications:

https://www.ncbi.nlm.nih.gov/sites/myncbi/1d_Bkr504nQAT/bibliography/46089723/public/?sort=date&direction=ascending

 

 

Research Interests

1. Our group has shown that T cells are key cellular players in modifying behaviors of anxiety and depressive-like behavior. We were among the first to employ the Rag2-/- mice model of lymphocyte deficiency in tests of stress responsiveness and the first to show that these mice display resistance to the effects of posttraumatic anxiety. We also showed that the absence of lymphocytes in Rag2-/- mice results in impaired recovery from sickness after an inflammatory immune challenge. Recent work using cells from GFP-expressing transgenic mice has confirmed that T cells expand and traffic to the brain in normal conditions owing to the possibility of a brain specific T cell subtype. More recently, we reported on beneficial effects of CD4+ T cells on anxiety and depressive-like behaviors and enhancement of memory processes. Overall, these studies have shown that T cells may have either beneficial and detrimental effects on emotionality depending on the stressor paradigm and the T cell subtype involved in the response.

2. The long-term goal of my research program has been to understand how peripheral inflammatory processes affect brain function, behavior and emotional processing. In addition to having expertise using the classical model of intraperitoneal LPS challenge, our group has developed additional mice and rat models of peripheral inflammation including nasal inflammation and allergies. We have shown that inflammatory processes in the upper respiratory tract also result in cytokine expression in the brain and altered behavioral responses indicative of anxiety and depression without inducing sickness behavior. My laboratory and trainees are recognized among my colleagues for this type of work.

3. One area of expertise included in our portfolio is the detection of immune genes and immune cells in the central nervous system. We have generated numerous articles showing constitutive expression of several immune genes in the brain as well as the induction of immune gene expression in the CNS in response to peripheral inflammation. We have shown how peripheral inflammatory processes can be transduced in the brain by several mechanisms without the need of compromising the blood brain barrier. We have mastered the “art” of in situ hybridization histochemistry (ISH) for detection of cytokines and other immune genes in the CNS and we continue to develop this expertise by incorporating new approaches through collaborations with other experts in the field of ISH, immunohistochemistry and microscopy.

4. The ultimate objective of our basic research program is to translate our basic animal research findings to humans. We have lead postmortem human studies on brain expression of cytokines and inflammatory markers in psychiatric conditions with focus on depressive disorders and suicide. We have reported on brain expression of pro- and anti-inflammatory cytokines in depression and suicide and were the first to report on tissue concentrations of kynurenines in the human prefrontal cortex. Moreover, we have participated in clinical studies showing that systemic inflammation is associated with psychiatric conditions including depression, anxiety and suicide. We have evaluated peripheral inflammatory markers including cytokines in a significant number of psychiatric patients and are one of the only groups studying the association of allergic inflammation with anxiety, depression and suicide.