Recent data demonstrates that the peripheral immune system has important effects on neuronal integrity and function in the CNS. This data includes work from our lab and others showing that deficits in neurobehavioral performance and motor neuron regeneration following axotomy are associated with the absence of functional T and B lymphocytes in immunodeficient mice. Moreover, alterations in neuronal function in immunodeficient mice can be prevented if normal lymphocytes from wild-type mice of the same genetic background are adoptively transferred to reconstitute a functional immune system in these animals. The proposed studies are designed to elucidate the neurobiological and immunological mechanisms that modulate these important processes in both limbic and motor neurons.
The Specific Aims will identify critical mechanisms that determine whether immunological processes are involved in modulating parameters of brain function and behavior, and may have proregenerative effects on injured neurons.
These aims are: 1) Test the hypothesis that immune status during development serves as a determinant of behavior; 2) Test the hypothesis that immunodeficiency results in alterations in septal and hippocampal neurons; and 3) Test the hypotheses that the proregenerative effects of immune reconstitution are mediated principally by T lymphocytes, and that their proregenerative function may be augmented by prior exposure to neuronal damage.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
1R01NS048472-01A1
Application #
6874012
Study Section
Neuroendocrinology, Neuroimmunology, and Behavior Study Section (NNB)
Program Officer
Utz, Ursula
Project Start
2005-02-25
Project End
2009-01-31
Budget Start
2005-02-25
Budget End
2006-01-31
Support Year
1
Fiscal Year
2005
Total Cost
$333,523
Indirect Cost
Name
University of Florida
Department
Psychiatry
Type
Schools of Medicine
DUNS #
969663814
City
Gainesville
State
FL
Country
United States
Zip Code
32611
Petitto, John M; Huang, Zhi; Meola, Danielle et al. (2012) Interleukin-2 and the septohippocampal system: intrinsic actions and autoimmune processes relevant to neuropsychiatric disorders. Methods Mol Biol 829:433-43
Huang, Zhi; Meola, Danielle; Petitto, John M (2012) Dissecting the effects of endogenous brain IL-2 and normal versus autoreactive T lymphocytes on microglial responsiveness and T cell trafficking in response to axonal injury. Neurosci Lett 526:138-43
Dauer, Daniel J; Huang, Zhi; Ha, Grace K et al. (2011) Age and facial nerve axotomy-induced T cell trafficking: relation to microglial and motor neuron status. Brain Behav Immun 25:77-82
Ha, Grace K; Parikh, Shivani; Huang, Zhi et al. (2008) Influence of injury severity on the rate and magnitude of the T lymphocyte and neuronal response to facial nerve axotomy. J Neuroimmunol 199:18-23
Ha, Grace K; Huang, Zhi; Parikh, Ravi et al. (2007) Immunodeficiency impairs re-injury induced reversal of neuronal atrophy: relation to T cell subsets and microglia. Exp Neurol 208:92-9
Huang, Zhi; Ha, Grace K; Petitto, John M (2007) IL-15 and IL-15R alpha gene deletion: effects on T lymphocyte trafficking and the microglial and neuronal responses to facial nerve axotomy. Neurosci Lett 417:160-4
Ha, Grace K; Huang, Zhi; Petitto, John M (2007) Prior facial motor neuron injury elicits endogenous T cell memory: relation to neuroregeneration. J Neuroimmunol 183:111-7
Ha, Grace K; Huang, Zhi; Streit, Wolfgang J et al. (2006) Endogenous T lymphocytes and microglial reactivity in the axotomized facial motor nucleus of mice: effect of genetic background and the RAG2 gene. J Neuroimmunol 172:1-8