Developmental neuroscience
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Adolescence has frequently been characterized as a period of increased risk taking, which may be largely driven by maturational changes in neural areas that process incentives. To investigate age- and gender-related differences in reward processing, we recorded event-related potentials (ERPs) from 80 participants in a gambling game, in which monetary wins and losses were either large or small. We measured two ERP components: the feedback-related negativity (FRN) and the feedback P3 (fP3). ⋯ Furthermore, adolescent boys showed both delayed FRNs to high losses and less differentiation in FRN amplitude between wins and losses in comparison to girls. The fP3, which is thought to index the salience of the feedback at a more conscious level than the FRN, was also larger in boys than in girls. Taken together, these results imply that higher levels of risk taking that are commonly reported in adolescent males may be driven both by hypersensitivity to high rewards and insensitivity to punishment or losses.
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Preadolescent animals display protracted hormonal stress responses mediated by the hypothalamic-pituitary-adrenal (HPA) axis compared to adults. Though the mechanisms that underlie this shift in stress reactivity are unknown, reduced glucocorticoid-dependent negative feedback on the HPA axis has been posited to contribute to this differential responsiveness. As the glucocorticoid receptors (GRs) are integral to this feedback response, we hypothesize that prior to puberty there will be fewer GRs in the neural-pituitary network that mediate negative feedback. ⋯ Additionally, we assessed stress-induced plasma adrenocorticotropic hormone and corticosterone in prepubertal (30 days old) and adult (70 days old) male rats and examined GR protein levels via Western blot in the brain and pituitary. We found that despite substantial adolescent-related changes in hormonal responsiveness, no significant differences were found between these ages in GR protein levels in regions that are important in negative feedback, including the medial prefrontal cortex, paraventricular nucleus of the hypothalamus, hippocampal formation, and pituitary. These data indicate that the extended hormonal stress response exhibited by preadolescent animals is independent of significant pubertal changes in GR protein levels.
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Fluoxetine (Flx; brand names Prozac, Sarafem, Rapiflux), a selective serotonin reuptake inhibitor, is prescribed for the treatment of depression in pregnant women; however, this commonly prescribed medication could affect fetal brain development as Flx crosses the placenta. The available data concerning the anatomical and behavioural consequences of perinatal exposure to Flx during early development on adult behaviour are limited and often contradictory. ⋯ Our results suggest that while perinatal exposure to Flx may have long-term effects on adult behaviour, these effects appear limited and not necessarily detrimental.
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Autism spectrum disorder (ASD) is a highly prevalent neurodevelopmental disorder characterized by abnormal social interactions, communication deficits and stereotyped or repetitive behaviors. Although the etiology of ASD remains elusive, converging lines of research indicate that mitochondrial dysfunction may play a substantive role in disease pathophysiology. Without an established causal link, the generation of therapeutic targets for ASD has been relatively unsuccessful and has focused solely on individual symptoms. ⋯ In addition, while prenatal exposure to VPA altered mitochondrial respiration, the KD was able to restore aspects of bioenergetic dysfunction. As the KD was able to modify complex social behaviors and mitochondrial respiration, it may be a useful treatment option for ASD. Future studies will need to examine the effectiveness of the KD to reverse the two additional core deficits of ASD and to explore various treatment regimens to determine optimal treatment duration and formulation.
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Apoptosis contributes greatly to the morphological and biochemical features of cell death after neonatal cerebral hypoxia-ischemia (HI), making this mode of cell death a promising therapeutic target. We previously showed that 10 mg/kg of the caspase inhibitor Q-VD-OPh at the onset of and immediately after HI on postnatal day 9 reduced brain infarct volume. In this study, delayed administration of Q-VD-OPh, 12 and 36 h after HI, decreased HI-induced caspase-3 activity (DEVD cleavage) by 23% and diminished the levels of the proinflammatory chemokines CCL2 (MCP-1) and CCL3 (MIP-1α) by 29.3 and 29.1%, respectively, but not the levels of the anti-inflammatory cytokines IL-4 and IL-10. ⋯ Q-VD-OPh treatment also ameliorated the loss of sensorimotor function, as evaluated by a cylinder rearing test (Q-VD-OPh: 30.8±4.3% vs. vehicle: 59.7±6.3% in nonimpaired forepaw preference) 3 weeks after HI, and reduced HI-induced hyperactivity, as measured in an open field test (Q-VD-OPh: 4,062±198 cm vs. vehicle: 4,792±205 cm in distance moved) 7 weeks after the insult. However, the functional protection was no longer observed when analyzed again at later time points. The mechanisms underlying the discrepancy between sustained morphological protection and transient functional protection remain to be elucidated.