Our long-term goal is to identify the neurochemical mechanisms that are associated with the functional-morphological changes responsible for observed decrements in physiological function with aging. Adrenergic transmitters, neuropeptide Y (NPY), and angiogenic II (ANG II) cause hypertension, increase ingestive behavior, inhibit sexual function, modify pituitary hormone section (for gonadotropin secretion the nature of the modification [stimulatory or inhibitory] is determined by the prevailing sex steroid milieu), modify activity and affect, and regulate energy balance. In brain, and sympathetic neurons (and the adrenal medulla), NPY is extensively co-localized with adrenergic transmitters. Further, ANG II potential the release of adrenergic transmitters and NPY from adrenergic transmitters. We proposed that dynamic changes in the hormonal milieu influence age- and experience-related changes in adrenergic-neuropeptide interactions. More specifically, we suggest that age-related changes in function/gene expression of alpha-2-adrenergic, NPY and ANG II receptors are major contributors to the age-related decrements in cardiovascular, sexual, and cognitive function.
Our Specific Aims are to test the following hypotheses: [1] alpha-2- adrenergic, Y1, Y5, and AT1a receptors exhibit dynamic changes in function with aging. The nature and extent of these functional changes is determined by the preceding sex steroid exposure and behavioral history of the individual. Further, the nature and extent of these changes dictate the degree of age-related alterations in cardiovascular, sexual, and cognitive function; [2]. The regulation of alpha 2 adrenergic, Y1, Y5, and AT1a receptor function/gene expression is modified by hormonal by hormonal deprivation/replacement. Specifically, androgen deprivation modifies receptor function/gene expression in a neural site- selective/specific manner. Further, varying the length of the hormonal hiatus, as well as the age at which it occurs, differentially affects physiological and behavioral, as well as adrenergic/neuropeptide, function. These studies will establish the """"""""normal"""""""" patterns of age-related changes in blood pressure, sexuality, and cognition in individual male rats, which will be correlated to changes in adrenergic transmitter, NPY, and ANG II function. The results will provide a unique contribution to understanding of age-associated alterations in adrenergic-neuropeptide interactions (and how they are modified by gonadal hormones) in the regulation of physiological function and behavior. The data will allow for a clear separation of the effects of age per se, behavioral experience and hormonal deprivation/replacement, with specific correlations to neural site-specific/selective changes in adrenergic, NPY, and ANG II receptor function/gene expression.

Project Start
2001-08-01
Project End
2002-07-31
Budget Start
Budget End
Support Year
30
Fiscal Year
2002
Total Cost
Indirect Cost
Name
Meharry Medical College
Department
Type
DUNS #
City
Nashville
State
TN
Country
United States
Zip Code
37208
Pulliam, Stephanie R; Pellom Jr, Samuel T; Shanker, Anil et al. (2016) Butyrate regulates the expression of inflammatory and chemotactic cytokines in human acute leukemic cells during apoptosis. Cytokine 84:74-87
Chen, Chau-Kuang; Bruce, Michelle; Tyler, Lauren et al. (2013) Analysis of an environmental exposure health questionnaire in a metropolitan minority population utilizing logistic regression and Support Vector Machines. J Health Care Poor Underserved 24:153-71
Boadi, William Y; Harris, Shalandus; Anderson, Justin B et al. (2013) Lipid peroxides and glutathione status in human progenitor mononuclear (U937) cells following exposure to low doses of nickel and copper. Drug Chem Toxicol 36:155-62
Choudhury, Shahana A; Ladson, Gwinnett; Kabir, Madina S (2012) Evaluation of serotype-specific immunity to Streptococcus pneumoniae in pregnant women and cord blood of infants: impact of race and ethnicity. J Natl Med Assoc 104:251-7
Hall 3rd, Mack; Misra, Smita; Chaudhuri, Minu et al. (2011) Peptide aptamer mimicking RAD51-binding domain of BRCA2 inhibits DNA damage repair and survival in Trypanosoma brucei. Microb Pathog 50:252-62
Kawai, Yumiko; Garduño, Lakisha; Theodore, Melanie et al. (2011) Acetylation-deacetylation of the transcription factor Nrf2 (nuclear factor erythroid 2-related factor 2) regulates its transcriptional activity and nucleocytoplasmic localization. J Biol Chem 286:7629-40
Rana, Tanu; Misra, Smita; Mittal, Mukul K et al. (2011) Mechanism of down-regulation of RNA polymerase III-transcribed non-coding RNA genes in macrophages by Leishmania. J Biol Chem 286:6614-26
Farrow, Anitra L; Rana, Tanu; Mittal, Mukul K et al. (2011) Leishmania-induced repression of selected non-coding RNA genes containing B-box element at their promoters in alternatively polarized M2 macrophages. Mol Cell Biochem 350:47-57
Sharma, Shvetank; Singha, Ujjal K; Chaudhuri, Minu (2010) Role of Tob55 on mitochondrial protein biogenesis in Trypanosoma brucei. Mol Biochem Parasitol 174:89-100
Sheng, Liu; Ding, Xinxin; Ferguson, Marcus et al. (2010) Prenatal polycyclic aromatic hydrocarbon exposure leads to behavioral deficits and downregulation of receptor tyrosine kinase, MET. Toxicol Sci 118:625-34

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