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981.
Kabir ZD Lourenco F Byrne ME Katzman A Lee F Rajadhyaksha AM Kosofsky BE 《Developmental neuroscience》2012,34(2-3):184-197
Prenatal cocaine exposure leads to persistent alterations in the growth factor brain-derived neurotrophic factor (BDNF), particularly in the medial prefrontal cortex (mPFC) and hippocampus, brain regions important in cognitive functioning. BDNF plays an important role in the strengthening of existing synaptic connections as well as in the formation of new contacts during learning. A single nucleotide polymorphism in the BDNF gene (Val66Met), leading to a Met substitution for Val at codon 66 in the prodomain, is common in human populations, with an allele frequency of 20-30% in Caucasians. To study the interaction between prenatal cocaine exposure and BDNF, we have utilized a line of BDNF Val66Met transgenic mice on a Swiss Webster background in which BDNF(Met) is endogenously expressed. Examination of baseline levels of mature BDNF protein in the mPFC of prenatally cocaine-treated wild-type (Val66Val) and Val66Met mice revealed significantly lower levels compared to prenatally saline-treated mice. In contrast, in the hippocampus of prenatally saline- and cocaine-treated adult Val66Met mice, there were significantly lower levels of mature BDNF protein compared to Val66Val mice. In extinction of a conditioned fear, we found that prenatally cocaine-treated Val66Met mice had a deficit in recall of extinction. Examination of mature BDNF protein levels immediately after the test for extinction recall revealed lower levels in the mPFC of prenatally cocaine-treated Val66Met mice compared to saline-treated mice. However, 2 h after the extinction test, there was increased BDNF exons I, IV, and IX mRNA expression in the prelimbic cortex of the mPFC in the prenatally cocaine-treated BDNF Val66Met mice compared to prenatally saline-treated mice. Taken together, our results suggest the possibility that prenatal cocaine-induced constitutive alterations in BDNF mRNA and protein expression in the mPFC differentially poises animals for alterations in behaviorally induced gene activation, which are interactive with BDNF genotype and differentially impact those behaviors. Such findings in our prenatal cocaine mouse model suggest a gene X environment interaction of potential clinical relevance. 相似文献
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Globally, obesity is affecting an increasing proportion of children. Physical activity plays an important role in the prevention of becoming overweight and obese in childhood and adolescence, and reducing the risk of obesity in adulthood. Puberty and the following adolescent period are acknowledged as particularly vulnerable times for the development of obesity due to sexual maturation and, in many individuals, a concomitant reduction in physical activity. In many Western settings, a large proportion of children and adolescents do not meet recommended physical activity guidelines and, typically, those who are more physically active have lower levels of body fat than those who are less active. Active behaviours have been displaced by more sedentary pursuits which have contributed to reductions in physical activity energy expenditure. Without appropriate activity engagement there is an increased likelihood that children will live less healthy lives than their parents. Owing to the high risk of overweight adolescents becoming obese adults, the engagement of children and adolescents in physical activity and sport is a fundamental goal of obesity prevention. 相似文献
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