The number of brain mast cells increases under specific social, stressful, and disease states. Also important, is the discovery that brain mast cells can cross the BBB. Although mast cells are best known for their role in mediating allergic reactions, it has become increasingly evident that they also play a protective role in defense against bacterial infection. Mast cells are heterogeneous, and their mediator content is dependent on their microenvironment, suggesting that brain mast cells should be studied as a unique population - as distinct from those in the periphery. The present application proposes to develop a mouse model which will be used in understanding the phenomenology and functional consequences of mast cells in the brain. Pilot data indicate that mast cell deficient animals lack a complete Acute Phase Response (APR) to bacterial infection. To examine the involvement of mast cells in mounting an immune response, we explore 2 social/behavioral/endocrine conditions in which the brain mast cell population is augmented: a cohabitation paradigm and a stress paradigm. Next, we test the hypothesis that prior exposure (which increases brain mast cell numbers) results in altered response to challenge of the immune system in mast cell rich brain loci. Specifically, we ask whether the mast cell number, activation state is augmented when their numbers in the brain are elevated. To test the hypothesis that brain mast cells have immunological consequences, we determine if increased mast cell numbers results in altered T cell surveillance in mast cell rich brain regions. We propose to test these hypotheses in mast cell deficient mice, in their wild type littermates and in mast cell reconstituted animals. This application will determine whether mast cells play a role in mounting an immune response in the brain.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21MH067782-02
Application #
6723759
Study Section
Special Emphasis Panel (ZRG1-IFCN-1 (03))
Program Officer
Winsky, Lois M
Project Start
2003-04-01
Project End
2006-03-31
Budget Start
2004-04-01
Budget End
2005-03-31
Support Year
2
Fiscal Year
2004
Total Cost
$163,500
Indirect Cost
Name
Columbia University (N.Y.)
Department
Psychology
Type
Other Domestic Higher Education
DUNS #
049179401
City
New York
State
NY
Country
United States
Zip Code
10027
Knolhoff, Ann M; Nautiyal, Katherine M; Nemes, Peter et al. (2013) Combining small-volume metabolomic and transcriptomic approaches for assessing brain chemistry. Anal Chem 85:3136-43
Nautiyal, Katherine M; Dailey, Christopher A; Jahn, Jaquelyn L et al. (2012) Serotonin of mast cell origin contributes to hippocampal function. Eur J Neurosci 36:2347-59
Nautiyal, Katherine M; Liu, Charles; Dong, Xin et al. (2011) Blood-borne donor mast cell precursors migrate to mast cell-rich brain regions in the adult mouse. J Neuroimmunol 240-241:142-6
Nautiyal, Katherine M; McKellar, Heather; Silverman, Ann-Judith et al. (2009) Mast cells are necessary for the hypothermic response to LPS-induced sepsis. Am J Physiol Regul Integr Comp Physiol 296:R595-602
Khalil, Mona; Ronda, Jocelyn; Weintraub, Michael et al. (2007) Brain mast cell relationship to neurovasculature during development. Brain Res 1171:18-29
Wilhelm, M; Silver, R; Silverman, A J (2005) Central nervous system neurons acquire mast cell products via transgranulation. Eur J Neurosci 22:2238-48