Methamphetamine induces low levels of neurogenesis in striatal neuron subpopulations and differential motor performance.

Methamphetamine (METH) causes significant loss of some striatal projection and interneurons. Recently, our group reported on the proliferation of new cells 36 h after METH and some of the new cells survive up to 12 weeks (Tulloch et al., Neuroscience 193:162-169, 2011b). We hypothesized that some of these cells will differentiate and express striatal neuronal phenotypes. To test this hypothesis, mice were injected with METH (30 mg/kg) followed by a single BrdU injection (100 mg/kg) 36 h after METH. One week after METH, a population of BrdU-positive cells expressed the neuronal progenitor markers nestin (18 %) and ß-III-tubulin (30 %). At 8 weeks, 14 % of the BrdU-positive cells were also positive for the mature neuron marker, NeuN. At 12 weeks, approximately 7 % of the BrdU-positive cells co-labeled with ChAT, PV or DARPP-32. We measured motor coordination on the rotarod and psychomotor activity in the open-field. At 12 weeks, METH-injected mice exhibited delayed motor coordination deficits. In contrast, open-field tests revealed that METH-injected mice compared to saline mice displayed psychomotor deficits at 2.5 days but not at 2 or more weeks after METH. Taken together, these data demonstrate that some of the new cells generated in the striatum differentiate and express the phenotypes of striatal neurons. However, the proportion of these new neurons is low compared to the proportion that died by apoptosis 24 h after the METH injection. More studies are needed to determine if the new neurons are functional.

Methamphetamine induces striatal cell death followed by the generation of new cells and a second round of cell death in mice.

Our laboratory has been investigating the impact of a neurotoxic exposure to methamphetamine (METH) on cellular components of the striatum post-synaptic to the dopaminergic terminals. A systemic bolus injection of METH (30 mg/kg, ip) induces the production of new cells in the striatum during a period lasting from 24-48 hours after METH. The newly generated cells arise from dormant striatal progenitors and not from the subventricular zone. The newly generated cells display glial phenotypes and begin to die 24 hours after birth, or 2.5 days post-METH. The protracted phase of cell death lasts for at least three months post-METH at which time the bulk of the newly generated cells have disappeared. The METH-induced production of new cells is associated with enlarged striatal volume (up to 50% larger than controls in some animals). As the newly generated cells die over a period of three months, the enlarged striatal volume normalizes. In conclusion, a neurotoxic dose of METH induces the generation of new cells in the striatum associated with enlarged striatal volume. The new cells die over three months post-METH and the enlarged striatal volume returns to control levels. This observation is significant because studies involving METH users show striatal enlargement and the normalization of striatal volume in METH users who have been abstinent for up to 20 months.

A single high dose of methamphetamine induces apoptotic and necrotic striatal cell loss lasting up to 3 months in mice.

Methamphetamine (METH) is an addictive agent that poses a public health problem due to its toxic effects on neural tissue. We have shown that METH induces striatal lesions (cell loss) within 24 h of administration. Because cell proliferation has been found to follow excitotoxic and other types of lesions in adult brain, we tested the hypothesis that cell proliferation would follow METH-induced striatal cell death. To that end, METH (30 mg/kg i.p.) was injected into adult male mice followed by a single injection of the proliferation marker 5-bromo-2'-deoxyuridine (BrdU, 100 mg/kg i.p.) at various times post-METH up to 12 weeks. Immunohistochemical analysis of striatal tissue showed that METH-treated animals incorporated BrdU between 24-48 h post-METH. To determine the survival of the newly generated cells, a subgroup of animals received BrdU 36 h after METH and were sacrificed at various times up to 12 weeks post-METH. Morphological analysis of striatal tissue from these animals showed that by 12 weeks post-METH, approximately 42% and 30% of the newly generated cells showed pyknotic or necrotic morphology, respectively. Thus, approximately 30% of the newly generated cells survive up to 12 weeks post-METH. Striatal volume was increased by METH and normalized to control levels by 12 weeks after METH. The data demonstrate that a single bolus injection of METH induces cellular changes and responses that persist for months after exposure to METH.

[Validation of the SCOFF questionnaire for screening the eating behaviour disorders of adolescents in school]. / Validación del cuestionario SCOFF para el cribado de los trastornos del comportamiento alimentario en adolescentes escolarizadas.

OBJECTIVE: To determine the internal consistency and criteria validity of the SCOFF questionnaire for screening adolescent eating behaviour disorders. DESIGN: Validation study with stochastic sampling. SETTING: Three schools at Bucaramanga, Colombia. PARTICIPANTS: 241 students selected at random from 1595 possible ones. MAIN INTERVENTIONS: SCOFF questionnaire and semi-structured CIDI interview, administered independently. MAIN MEASUREMENTS: Social and personal details, Cronbach's alpha, sensitivity analysis, specificity, forecast values, Cohen mean kappa test, and ROC curve. RESULTS: Sensitivity found was 81.9% (95% CI, 70.7-89.7) and specificity, 78.7% (95% CI, 71.7-84.6). The area under the ROC curve was 0.8596 (95% CI, 0.8108-0.9084); the Cronbach's alpha test, 0.436, and the Cohen mean kappa, 0.554 (95% CI, 0.425-0.683). CONCLUSIONS: The SCOFF questionnaire is an acceptable alternative for screening groups of adolescents because of its simplicity and speed of administration.

Development of a SCAR marker linked to the I gene in common bean.

Two 24-mer SCAR primers (SW13) were developed from a previously identified 10-mer RAPD primer (OW13(690)) linked to the I gene, which conditions resistance to bean common mosaic virus (BCMV) in common bean. Linkage between SW13 and the I gene was tested in three F2 populations segregating for both SW13 and the I gene: N84004/Michelite (1.0 +/- 0.7 cM), Seafarer/UI-114 (1.3 +/- 0.8 cM), and G91201/Alpine (5.0 +/- 2.2 cM). SW13 proved to be more specific and reproducible than the OW13(690) RAPD marker. Using different heat-stable DNA polymerases, SW13 amplified a single 690-bp fragment linked to the I gene that more consistently permitted the identification of resistant plants. In addition, the presence of the I gene was detected using SW13 in genotypes originating from different gene pools of Phaseolus vulgaris L., indicating a broad utility of this marker for bean breeding programs.

Heterogeneous inbred populations are useful as sources of near-isogenic lines for RAPD marker localization.

The development and use of RAPD markers for applications in crop improvement has recently generated considerable interest within the plant breeding community. One potential application of RAPDs is their use for "tagging" simply-inherited (monogenic) pest-resistance genes and enabling more efficient identification and selection of genotypes carrying specific combinations of resistance genes. In this report, we propose and describe the use of heterogeneous inbred populations as sources of near-isogenic lines (NILs) for targeting RAPD markers linked to major pest resistance genes. The development of these NILs for RAPD marker analyses involved a sequence of line and mass selection during successive generations of inbreeding. DNA bulks derived from the NILs were used to identify a RAPD marker (designated OK14620, generated by 5'-CCCGCTACAC-3' decamer) that was tightly linked (2.23±1.33 centiMorgans) to an important rust [Uromyces appendiculatus (Pers.) Unger var. appendiculatus] resistance gene (Ur-3) in common bean (Phaseolus vulgaris L.). The efficiency of this approach was demonstrated by a low rate of false-positives identified, the tightness of the linkage identified, and the ability to detect polymorphism between genomic regions that are representative of the same gene pool of common bean. This method of deriving NILs should find application by researchers interested in utilizing marker-assisted selection for one or more major pest resistance genes. The identification of OK14620 should help to facilitate continued use of the Ur-3 resistance source and will now enable marker-assisted pyramiding of three different bean rust resistance sources (two previously tagged) to provide effective and stable resistance to this important pathogen.