Altered function of the neurotransmitter, glutamate, has been implicated in many brain disorders, including ischemia (stroke), Alzheimer's disease and Huntington's disease. The cellular degeneration, caused by glutamate excitotoxicity, can be manifested as motor, sensory or learning disabilities. In this proposal, we will study the local and global effects of how neurons are affected by glutamate dysfunction using the spastic Han Wistar mutant which develops excitotoxicity in an age-dependent manner. This rat possesses a naturally occurring genetic mutation which shows an abnormal degeneration of neurons in two brain regions that are susceptible to glutamate toxicity: cerebellum and hippocampus. This proposal will address the various intracellular interactions that occur during excitotoxicity inherent produced in the sHW rat. Including: the potential role of intracellular calcium, the mode of cell death that is occurring in sHW cerebellum and hippocampus, mapping the glutamate receptor profile in the sHW CNS and examining the dimension of synaptic reorganization. In summary, we will experimentally follow the molecular and biochemical time course of neurological disorder, identifying how the central nervous system (CNS) reacts to the interactions of environment and the cells that are destined for degeneration. The potential benefit resulting from these experiments will be to ascertain the complex interactions of both the affected cell and those that may be affected by molecular and biochemical compensation. Ultimately, we believe that this research will lead to the establishment of new neuroprotective schemes for victims of glutamate excitotoxic disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Minority Biomedical Research Support - MBRS (S06)
Project #
5S06GM048680-09
Application #
6642307
Study Section
Minority Programs Review Committee (MPRC)
Project Start
2002-07-01
Project End
2003-06-30
Budget Start
Budget End
Support Year
9
Fiscal Year
2002
Total Cost
Indirect Cost
Name
California State University Northridge
Department
Type
DUNS #
055752331
City
Northridge
State
CA
Country
United States
Zip Code
91330
Alpizar, David; Laganá, Luciana; Plunkett, Scott W et al. (2018) Evaluating the eight-item Patient Health Questionnaire's psychometric properties with Mexican and Central American descent university students. Psychol Assess 30:719-728
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Maciel, Michelle; Laganà, Luciana (2014) Older women's sexual desire problems: biopsychosocial factors impacting them and barriers to their clinical assessment. Biomed Res Int 2014:107217
Diamante, Graciel; Phan, Claire; Celis, Angie S et al. (2014) SAW1 is required for SDSA double-strand break repair in S. cerevisiae. Biochem Biophys Res Commun 445:602-7
Laganà, Luciana; Bloom, David William; Ainsworth, Andrew (2014) Urinary incontinence: its assessment and relationship to depression among community-dwelling multiethnic older women. ScientificWorldJournal 2014:708564
Laganá, Luciana; White, Theresa; Bruzzone, Daniel E et al. (2013) Exploring the Sexuality of African American Older Women. Br J Med Med Res 4:1129-1148

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