Postmortem studies: Based on the phenomena that peripheral inflammation may be "reflected" into the brain as "molecular inflammation" expressed as increases in cytokine levels, we compared relative amount of mRNA for inflammatory cytokines (allergic and innate) in the brain of victims of suicide with respect to controls. We reported for the first time constitutive expression of several mRNA species in the frontal cortex of the human brain and their increases in victims of suicide. These results were published in Acta Psychiatrica Scandinavica 2008).
Clinical studies: Collaborative efforts of the LBNI with members of the MAP were aimed at evaluating the peripheral inflammatory characteristics of people suffering from mood disorders. Based on the marked seasonal oscillation in the incidence of unipolar and bipolar depressive disorders, it was hypothesized that these seasonal changes were related with seasonal inflammatory processes of the airways. These studies resulted in several publications including Journal of Affective Disorders, 2007, International Journal of Child Health and Human Development 2008 and Scientific World Journal 2008.
Lab Techniques and EquipmentBehavioral
Most of our behavioral analysis systems are based on the digital video softwares developed by Cleversys Inc (http://ceversysinc.com). We were the first laboratory to validate the Forced Swim Scan in rats.
The following behavioral tests have been implemented in our laboratory:
ANXIETY: Open Field Test, Elevated Plus Maze Test, Light-Dark Box test, Social Interaction Test DEPRESSIVE-LIKE BEHAVIORS: Forced Swin Test, Tail Suspension Test and Consumption of Sweet Solutions
AGGRESSION: Resident-Intruder Test
STRESS RESPONSIVENESS: Acoustic Startle Test, Restraint Stress
Cloning and sequencing of mRNA's splice variants. Real-time RT-PCR using SYBR green and the My iQ instrument from Bio Rad. Radioactive in situ hybridization histochemistry using riborpobes. Western blots and immunohistochemistry.
Microscopy and Image Analysis
Film autoradiographic densitometry, Confocal microscopy.
Animal Models of Inflammatory Diseases
INTRANASAL IMMUNE CHALLENGE: Bacterial Lipopolysaccharides (LPS) (Innate immunity, TLR IV) Sensitization and Challenge with Ovoalbunin (OVA) and pollen (TH2 driven) Unmethylated CpG DNA sequences and Poly I:C. (Innate immunity)
Tonelli LH, Katz M, Kovacsics CE, Gould TD, Joppy B, Hoshino A, Hoffman G, Komarow H, Postolache TT (2009) Allergic rhinitis induces anxiety-like behavior and altered social interaction in rodents. Brain Behavior and Immunity (6):784-93.
Holmes A, Postolache TT, Tonelli LH (2008) Intranasal immune challenge induces sex-dependent depressive-like behavior and cytokine expression in the brain. Neuropsychopharmacology 33(5):1038-48
Tonelli LH, Stiller J, Rujescu D, Giegling I, Schneider B, Maurer K, Schnabel A, Moller H-J, Chen HH, Postolache TT (2008) Elevated cytokine expression in the orbitofrontal cortex of victims of suicide. Acta Psychiatrica Scandinavica 117(3):198-206
Guzman A., Tonelli LH, Roberts D., Stiller J., Jackson M.A., Soriano, J.J., Yousufi S., Rohan K.J., Komarow H., Postolache T.T. (2007) Mood worsening with high-pollen counts and seasonality: a preliminary report. Journal of Affective Disorders 101(1-3):269-74
Tonelli L.H. Postolache T.T (2005) Tumor necrosis factor alpha, interleukin-1 beta, interleukin-6 and major histocompatibility complex molecules in the normal brain and after peripheral immune challenge. Neurological Research 27(7):679-84.
Tonelli L.H., Postolache T.T., Sternberg E.M. (2005). Inflammatory genes and neural activity: Involvement of immune genes in synaptic function and behavior. Frontiers in Biosciences 1;10:675-80.
Tonelli L.H., Gunsolly C.A, Belyaskaya E., Atwood R.A., Sternberg E.M. (2004). Increased pro-thyrotropin-releasing hormone transcription in hypophysiotropic neurons of Lewis rats. Journal of Neuroimmunology 153(1-2):143-9.
Tonelli L.H., Maeda S., Rapp K.L., Sternberg E.M. (2003). Differential induction of interleukin-I beta mRNA in the brain parenchyma of Lewis and Fischer rats after peripheral injection of lipopolysaccharides. Journal of Neuroimmunology 140:126-33.
Tonelli L.H., Kramer P., Webster J.I., Listwak S., Wray S., Sternberg E.M. (2002). Lipoplysaccharide-induced estrogen receptors regulation in the hypothalamic paraventricular nucleus of Lewis and Fischer rats. Journal of Neuroendocrinology 14:847-852.