Tina Thompson

Modulation of mesolimbic dopaminergic activity over the rat estrous cycle.

Clinical observations have suggested that ovarian steroid hormones modulate the symptomology of psychiatric disorders and this modulation is thought to be due to a protective effect of estrogen on dopaminergic activity. To test this hypothesis, mesolimbic dopamine (DA) activity was examined in relationship to endogenous hormone levels. Using in vivo electrochemical techniques, K+-stimulated DA release was measured in the nucleus accumbens of control, intact cycling female rats and experimental rats which had received bilateral 6-hydroxydopamine (6-OHDA) lesions to the medial prefrontal cortex (PFC) to produce subcortical hyperactivity. DA release and reuptake fluctuated with changes in circulating steroid levels in both control and lesion groups. In non-lesioned control rats, stimulated DA release peaked during diestrus I (DI) and was attenuated during diestrus II (DII) and estrus. DA transport, as measured by a change in T1/2 time, was significantly potentiated during proestrus. The expression of subcortical hyperactivity following lesions to the medial PFC appeared to be dependent on the steroid environment; during DII an increased responsiveness was observed while a significant decrease in K+-stimulated release was observed during DI. These cyclic changes in DA release were not associated with dramatic changes in DA transport except during proestrus when transport was significantly prolonged. These data suggest that cyclic fluctuation of ovarian steroids may modulate DA activity presynaptically through an alteration in both release and reuptake and that this modulation effectively dampens the expression of subcortical hyperactivity except under specific hormonal conditions.

Attenuation of dopamine uptake in vivo following priming with estradiol benzoate

Dopamine (DA) uptake and clearance were examined using in vivo voltammetry following injection of DA (200 microM) into the nucleus accumbens of ovariectomized (OVX) or OVX-estrogen-primed rats (estradiol benzoate, EB, 10 microg 48 and 24 h prior to experiment). The rate of DA uptake was significantly attenuated in steroid-treated animals: this decrease was accompanied by a significant increase in DA clearance time. Quinpirole (0.5 mg/kg) modulated the kinetics of DA uptake in OVX but not EB-primed rats. These data suggest that DA clearance can be regulated by physiological doses of EB.

Adult-derived stem cells and their potential for use in tissue repair and molecular medicine.

This report reviews three categories of precursor cells present within adults. The first category of precursor cell, the epiblast‐like stem cell, has the potential of forming cells from all three embryonic germ layer lineages, e.g., ectoderm, mesoderm, and endoderm. The second category of precursor cell, the germ layer lineage stem cell, consists of three separate cells. Each of the three cells is committed to form cells limited to a specific embryonic germ layer lineage. Thus the second category consists of germ layer lineage ectodermal stem cells, germ layer lineage mesodermal stem cells, and germ layer lineage endodermal stem cells. The third category of precursor cells, progenitor cells, contains a multitude of cells. These cells are committed to form specific cell and tissue types and are the immediate precursors to the differentiated cells and tissues of the adult. The three categories of precursor cells can be readily isolated from adult tissues. They can be distinguished from each other based on their size, growth in cell culture, expressed genes, cell surface markers, and potential for differentiation. This report also discusses new findings. These findings include the karyotypic analysis of germ layer lineage stem cells; the appearance of dopaminergic neurons after implantation of naive adult pluripotent stem cells into a 6‐hydroxydopamine‐lesioned Parkinsons model; and the use of adult stem cells as transport mechanisms for exogenous genetic material. We conclude by discussing the potential roles of adult‐derived precursor cells as building blocks for tissue repair and as delivery vehicles for molecular medicine.

Estrogen priming modulates autoreceptor-mediated potentiation of dopamine uptake.

The ability of a physiological dose of estrogen (estradiol benzoate, estrogen: 10 microgram 48 and 24 h prior) to modulate autoreceptor-mediated changes in dopamine transport properties was investigated in a synaptosomal preparation prepared from the nucleus accumbens of ovariectomized rats. Quinpirole (1-100 microM)-mediated potentiation of [3H]dopamine uptake was attenuated in synaptosomes from estrogen-primed animals. Haloperidol (10 microM) inhibited basal uptake and effectively prevented quinpirole potentiation of uptake in both ovariectomized and estrogen-primed samples. The ability of selective protein phosphatase inhibitors to modulate autoreceptor-mediated potentiation of dopamine uptake was also examined. Pretreatment with protein phosphatase 2B (deltamethrin, cypermethrin) or protein phosphatase 1 (tautomycin) inhibitors attenuated basal and quinpirole-potentiated dopamine uptake in ovariectomized but not estrogen-primed tissue. These data suggest that autoreceptor-mediated activation of dopamine transport can be regulated by physiological doses of estrogen and implicate a role for protein phosphorylation in autoreceptor-mediated potentiation of dopamine uptake.

Modulation of dopamine uptake in rat nucleus accumbens: effect of specific dopamine receptor antagonists and sigma ligands

The ability of dopamine (DA) antagonists and sigma receptor ligands to alter [(3)H]-DA uptake was examined using synaptosomes prepared from the nucleus accumbens of female rats. Pre-incubation with compounds having a high affinity for sigma (rimcazole, haloperidol, and spiperone) receptors produced dose dependent inhibition of (3)H-DA uptake. Sulpiride, a pure DA D(2) antagonist had no effect. In contrast, DA uptake was potentiated in response to (+)-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine, a mixed sigma receptor antagonist and DA D(2) receptor agonist. Similarly, SKF-10,047, a selective sigma receptor agonist, and progesterone, a putative endogenous ligand for the sigma receptor, produced significant increases in (3)[H]-DA uptake. These data suggest a potential role for sigma and DA ligands in the regulation of DA uptake in the nucleus accumbens.

Roadmap for creating an accelerated three-year medical education program

ABSTRACT Medical education is undergoing significant transformation. Many medical schools are moving away from the concept of seat time to competency-based education and introducing flexibility in the curriculum that allows individualization. In response to rising student debt and the anticipated physician shortage, 35% of US medical schools are considering the development of accelerated pathways. The roadmap described in this paper is grounded in the experiences of the Consortium of Accelerated Medical Pathway Programs (CAMPP) members in the development, implementation, and evaluation of one type of accelerated pathway: the three-year MD program. Strategies include developing a mission that guides curricular development – meeting regulatory requirements, attaining institutional buy-in and resources necessary to support the programs, including student assessment and mentoring – and program evaluation. Accelerated programs offer opportunities to innovate and integrate a mission benefitting students and the public. Abbreviations: CAMPP: Consortium of accelerated medical pathway programs; GME: Graduate medical education; LCME: Liaison committee on medical education; NRMP: National residency matching program; UME: Undergraduate medical education

Can PBL Group Assignment Affect Examination Performance

Medical student examination performance in an integrated problem-based learning (PBL) curriculum related to group and faculty facilitator (tutor) assignment has not been well studied. The aim of this study is to investigate whether the PBL group and tutor to which a student is assigned affect examination performance. We found that only 3.6% of all groups had non-Gaussian student examination score distributions. Tutorial group average scores varied by less than 10% from the examination mean. Faculty tutor experience in PBL or expertise by either clinical or basic science background did not appear to have a significant effect upon student knowledge based examination performance, as measured within an integrated basic science PBL curriculum.