This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Early repetitive pain in premature babies and may lead to permanent changes in brain development, with abnormal pain processing, increased anxiety, poor cognition, attention deficit disorder, and behavioral problems during adolescence or adulthood. Repetitive pain in newborn rats was associated with increased neuronal cell death in widely distributed cortical and subcortical areas. Following puberty, pain-exposed rats showed greater anxiety, hypervigilance, preattentional and cognitive deficits; thus mimicking the long-term behavioral outcomes of ex-preterm children. Understanding the mechanisms mediating these effects may lead to novel therapeutic measures and improve the cognitive and behavioral outcomes of premature birth.
Aim 1 : Determination of critical windows will test the hypothesis that repetitive pain is associated with increased neuronal cell death during the most sensitive developmental stage(s). Increased neuronal vulnerability may be developmentally regulated in different neuroanatomical areas, and will be correlated with cognitive and behavioral outcomes evaluated in adult rats.
Aim 2 ' Investigation of cell death mechanisms will test the hypothesis that repetitive pain produces neuronal cell death by activating the signaling pathways leading to excitotoxicity via excitatory receptors. Pharmacological manipulations decreasing neuronal cell death will allow the development of novel therapeutic approaches, which will also be correlated with adult cognition and behavior.
Aim 3 ' Assessment ofpre-attentional processes in humans will test the hypothesis that abnormal regulation of arousal contributes to the cognitive deficits during adolescence or adulthood. A measure of arousal in humans, the P50 potential, will be compared between adolescents born preterm and matched term-bom adolescents, and correlated with their performance of attentional tasks (Psychomotor Vigilance Test) and executive functions (Operant Test Battery), and with relative frontal lobe blood flow (Near InfraRed Spectroscopy). The proposed research is designed to establish the PI as an independent clinician scientist with the help of established mentoring under the auspices of the Center for Translational Neuroscience.
| Odle, Angela; Allensworth-James, Melody; Childs, Gwen V (2018) The War on the Placenta: The Differing Battles of High-Fat Diet and Obesity. Endocrinology 159:1642-1643 |
| MacNicol, Melanie C; Cragle, Chad E; McDaniel, F Kennedy et al. (2017) Evasion of regulatory phosphorylation by an alternatively spliced isoform of Musashi2. Sci Rep 7:11503 |
| Rhee, Christopher J; Kaiser, Jeffrey R; Rios, Danielle R et al. (2016) Elevated Diastolic Closing Margin Is Associated with Intraventricular Hemorrhage in Premature Infants. J Pediatr 174:52-6 |
| Odle, Angela Katherine; Allensworth-James, Melody; Haney, Anessa et al. (2016) Adipocyte Versus Somatotrope Leptin: Regulation of Metabolic Functions in the Mouse. Endocrinology 157:1443-56 |
| Gannon, Brenda M; Williamson, Adrian; Suzuki, Masaki et al. (2016) Stereoselective Effects of Abused ""Bath Salt"" Constituent 3,4-Methylenedioxypyrovalerone in Mice: Drug Discrimination, Locomotor Activity, and Thermoregulation. J Pharmacol Exp Ther 356:615-23 |
| Rhee, Christopher J; Kibler, Kathleen K; Easley, R Blaine et al. (2016) The Diastolic Closing Margin Is Associated with Intraventricular Hemorrhage in Premature Infants. Acta Neurochir Suppl 122:147-50 |
| Odle, Angela K; Allensworth-James, Melody L; Akhter, Noor et al. (2016) A Sex-Dependent, Tropic Role for Leptin in the Somatotrope as a Regulator of POU1F1 and POU1F1-Dependent Hormones. Endocrinology 157:3958-3971 |
| MacNicol, Melanie C; Cragle, Chad E; Arumugam, Karthik et al. (2015) Functional Integration of mRNA Translational Control Programs. Biomolecules 5:1580-99 |
| Rhee, Christopher J; Fraser 3rd, Charles D; Kibler, Kathleen et al. (2015) Ontogeny of cerebrovascular critical closing pressure. Pediatr Res 78:71-5 |
| Odle, Angela K; Drew, Paul D; Childs, Gwen V (2015) Giant mice reveal new roles for GH in regulating the adipose immune microenvironment. Endocrinology 156:1613-5 |
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