Search

© 2019 Society for the Study of Addiction Worldwide consumption of opioids remains at historic levels. Preclinical studies report intergenerational effects on the endogenous opioid system of future progeny following preconception morphine exposure. Given the role of endogenous opioids in energy homeostasis, such effects could impact metabolism in the next generation. Thus, we examined diet-induced modifications in F1 male progeny of morphine-exposed female rats (MORF1). When fed a high fat-sugar diet (FSD) for 6 weeks, MORF1 males display features of emerging metabolic syndrome; they consume more food, gain more weight, and develop fasting-induced hyperglycemia and hyperinsulinemia. In the hypothalamus, proteins involved in energy homeostasis are modified and RNA sequencing revealed down-regulation of genes associated with neuronal plasticity, coupled with up-regulation of genes associated with immune, inflammatory, and metabolic processes that are specific to FSD-maintained MORF1 males. Thus, limited preconception morphine exposure in female rats increases the risk of metabolic syndrome/type 2 diabetes in the next generation.

Regular sprint interval training (SIT) improves whole-body aerobic capacity and muscle oxidative potential, but very little is known about knee extensor anabolic or fatigue resistance adaptations, or whether effects are similar for males and females. The purpose of this study was to compare sex-related differences in knee extensor size, torque-velocity relationship and fatigability adaptations to 12 weeks SIT.Sixteen males and fifteen females (mean (SEM) age: 41 (±2.5) yrs) completed measurements of total body composition assessed by DXA, quadriceps muscle cross-sectional area (CSAQ) assessed by MRI, the knee extensor torque-velocity relationship (covering 0 - 240°·sec) and fatigue resistance, which was measured as the decline in torque from the first to the last of 60 repeated concentric knee extensions performed at 180°·sec. SIT consisted of 4 x 20 second sprints on a cycle ergometer set at an initial power output of 175% of power at VO2max, three times per week for 12 weeks.CSAQ increased by 5% (p=0.023) and fatigue resistance improved 4.8% (p=0.048), with no sex differences in these adaptations (sex comparisons: p=0.140 and p=0.282, respectively). Knee extensor isometric and concentric torque was unaffected by SIT in both males and females (p>0.05 for all velocities).12 weeks SIT, totalling 4 minutes very intense cycling per week, significantly increased fatigue resistance and CSAQ similarly in males and females, but did not significantly increase torque in males or females. These results suggest that SIT is a time-effective training modality for males and females to increase leg muscle size and fatigue resistance.

© 2019 Society for the Study of Addiction Worldwide consumption of opioids remains at historic levels. Preclinical studies report intergenerational effects on the endogenous opioid system of future progeny following preconception morphine exposure. Given the role of endogenous opioids in energy homeostasis, such effects could impact metabolism in the next generation. Thus, we examined diet-induced modifications in F1 male progeny of morphine-exposed female rats (MORF1). When fed a high fat-sugar diet (FSD) for 6 weeks, MORF1 males display features of emerging metabolic syndrome; they consume more food, gain more weight, and develop fasting-induced hyperglycemia and hyperinsulinemia. In the hypothalamus, proteins involved in energy homeostasis are modified and RNA sequencing revealed down-regulation of genes associated with neuronal plasticity, coupled with up-regulation of genes associated with immune, inflammatory, and metabolic processes that are specific to FSD-maintained MORF1 males. Thus, limited preconception morphine exposure in female rats increases the risk of metabolic syndrome/type 2 diabetes in the next generation.

© 2018 The Authors Background & aims: There is a large body of evidence which supports the role of inflammation in the pathophysiology of mental health disorders, including depression. Dietary patterns have been shown to modulate the inflammatory state, thus highlighting their potential as a therapeutic tool in disorders with an inflammatory basis. Here we conduct a systematic review and meta-analysis of current literature addressing whether there is a link between the inflammatory potential of a diet and risk of depression or depressive symptoms. Methods: A systematic literature search was performed to identify studies that reported an association between the inflammatory potential of the diet and risk of depressive symptoms or diagnosis of depression. Random effect models were used to meta-analyse effect sizes. Quality assessment, publication bias, sensitivity and subgroup analyses were also performed. Results: Eleven studies, with a total of 101,950 participants at baseline (age range: 16–72 years old), were eligible for review. A significant association between a pro-inflammatory diet and increased risk of depression diagnosis or symptoms was evident, relative to those on an anti-inflammatory diet (OR: 1.40, 95% confidence intervals: 1.21–1.62, P < 0.001). No publication bias was detected; however, some study heterogeneity was evident (I2 = 63%, P < 0.001). Subgroup analyses suggested the main source of study heterogeneity was the study design (cross-sectional or longitudinal) and the effect measure used (odds ratio, hazard ratio or relative risk). Conclusion: These results provide an association between pro-inflammatory diet and risk of depression. Thus, adopting an anti-inflammatory diet may be an effective intervention or preventative means of reducing depression risk and symptoms.

The social environment of lactation is a key etiological factor for the occurrence of postpartum disorders affecting women and their children. Postpartum depression and anxiety disorders are highly prevalent in new mothers and negatively affect offspring's cognitive development through mechanisms which are still unclear. Here, using a rat model, we manipulated the maternal social environment during lactation and explored the pathways through which social isolation (vs. the opportunity for limited social interaction with another lactating female, from 1 day before parturition to postpartum day 16) and chronic social conflict (daily exposure to a male intruder from postpartum day 2 to day 16) affect offspring learning and memory, measured at 40 to 60 days of age. We specifically explored the consequences of these social treatments on two main hypothesized mediators likely to affect offspring neurophysiological development: the quality of maternal care and maternal inflammation factors (BDNF, GM‐CSF, ICAM‐1, TIMP‐1 and VEGF) likely to influence offspring development through lactation. Maternal rats which had the opportunity to interact with another lactating female spent more time with their pups which, in turn, displayed improved working and reference memory. Social stress affected maternal plasma levels of cytokines that were associated with cognitive deficits in their offspring. However, females subjected to social stress were protected from these stress‐induced immune changes and associated offspring cognitive impairment by increased social affiliation. These results underscore the effects of social interaction for new mothers and their offspring and can be used to inform the development of clinical preventative measures and interventions.

© 2018 Elsevier B.V. With increasing life expectancy, age-associated cognitive impairment is an escalating problem worldwide. Inflammation is one of the features that characterises cognitive decline and can stimulate neurodegeneration. Interleukin 6 (IL-6) is a cytokine frequently associated with a pro-inflammatory phenotype and increased levels have been associated with the pathogenesis of dementia. The rs1800796 polymorphism in the promoter region of IL-6 gene was previously shown to influence IL-6 expression and therefore we hypothesised this gene polymorphism would be associated with IL-6 plasma levels and cognitive performance of older adults. The present study investigated the association of the rs1800796 polymorphism on plasma IL-6 levels and cognition in healthy older adults (n = 207, 74.6 ± 3.4 years, 51% female) that participated in a Pan-European project (MyoAge). The participants were assessed for working memory capacity, executive functioning, episodic memory and global cognition using the Cambridge Neuropsychological Test Automated Battery CANTAB. Fasting plasma IL-6 levels were measured by ELISA and genotyping was performed using the KASP assay. Results showed that the rs1800796 polymorphism was in Hardy-Weinberg equilibrium (P =.16) with the minor allele (C) showing a frequency of 6.3%. There were no differences in plasma IL-6 concentrations between the GG-homozygotes and C-allele carriers (P =.22). The C-allele carriers performed worse on a measure of executive functioning (P =.035) and had lower global cognitive scores (P =.045), compared to GG-homozygotes. These differences remained significant after accounting for age, sex and prior cognitive abilities (P <.05 for both). There were no differences in measures of memory (episodic and working) between the genotypes group. These findings suggest that the rs1800796 variant may be detrimental for executive functioning, but not memory, in healthy older adults.

© 2018 Elsevier B.V. With increasing life expectancy, age-associated cognitive impairment is an escalating problem worldwide. Inflammation is one of the features that characterises cognitive decline and can stimulate neurodegeneration. Interleukin 6 (IL-6) is a cytokine frequently associated with a pro-inflammatory phenotype and increased levels have been associated with the pathogenesis of dementia. The rs1800796 polymorphism in the promoter region of IL-6 gene was previously shown to influence IL-6 expression and therefore we hypothesised this gene polymorphism would be associated with IL-6 plasma levels and cognitive performance of older adults. The present study investigated the association of the rs1800796 polymorphism on plasma IL-6 levels and cognition in healthy older adults (n = 207, 74.6 ± 3.4 years, 51% female) that participated in a Pan-European project (MyoAge). The participants were assessed for working memory capacity, executive functioning, episodic memory and global cognition using the Cambridge Neuropsychological Test Automated Battery CANTAB. Fasting plasma IL-6 levels were measured by ELISA and genotyping was performed using the KASP assay. Results showed that the rs1800796 polymorphism was in Hardy-Weinberg equilibrium (P =.16) with the minor allele (C) showing a frequency of 6.3%. There were no differences in plasma IL-6 concentrations between the GG-homozygotes and C-allele carriers (P =.22). The C-allele carriers performed worse on a measure of executive functioning (P =.035) and had lower global cognitive scores (P =.045), compared to GG-homozygotes. These differences remained significant after accounting for age, sex and prior cognitive abilities (P <.05 for both). There were no differences in measures of memory (episodic and working) between the genotypes group. These findings suggest that the rs1800796 variant may be detrimental for executive functioning, but not memory, in healthy older adults.

Background: Elevated biomarkers of systemic inflammation have been reported in individuals with cognitive decline, however, most of the literature concerns cross-sectional analyses that have produced mixed results. This study investigates the aetiology of this association by performing meta-analyses on prospective studies investigating the relationship between baseline interleukin-6 (IL-6), an established marker of peripheral inflammation, with cognitive decline risk in non-demented adults at follow-up. Methods: We reviewed studies reporting peripheral IL-6 with future cognitive decline, up to February 2017 by searching the PubMed, Science Direct, Scopus and Google Scholar databases. Studies which contained odds ratios (ORs) for the association between circulating baseline IL-6 and longitudinal cognitive performance in non-demented community dwelling older adults were pooled in random-effects models. Results: The literature search retrieved 5,642 potential articles, of which 7 articles containing 8 independent ageing cohorts were eligible for review. Collectively, these studies included 15,828 participants at baseline. Those with high circulating IL-6 were 1.42 times more likely to experience global cognitive decline at follow-up, over a 2 – 7-year period, compared to those with low IL-6 (OR 1.42, 95% CI 1.18 – 1.70; p < 0.001). Subgroup and sensitivity analyses suggests that this association is independent of the study sample size, duration of follow-up and cognitive assessments used. Conclusions: These results add further evidence for the association between high peripheral inflammation, as measured by blood IL-6, and global cognitive decline. Measuring circulating IL-6 may be a useful indication for future cognitive health.

Cognitive impairments are a prevalent and disabling non-motor complication of Parkinson’s disease, but with variable expression and progression. The onset of serious cognitive decline occurs alongside substantial cholinergic denervation, but imprecision of previously available techniques for in-vivo measurement of cholinergic degeneration limit their use as predictive cognitive biomarkers. However, recent developments in stereotactic mapping of the cholinergic basal forebrain have been found useful for predicting cognitive decline in prodromal stages of Alzheimer’s disease. These methods have not yet been applied to longitudinal Parkinson’s disease data. In a large sample of people with de novo Parkinson’s disease (N = 168), retrieved from the Parkinson’s Progressive Markers Initiative database, we measured cholinergic basal forebrain volumes, using morphometric analysis of T1-weighted images in combination with a detailed stereotactic atlas of the cholinergic basal forebrain nuclei. Using a binary classification procedure, we defined patients with reduced basal forebrain volumes (relative to age) at baseline, based on volumes measured in a normative sample (N = 76). Additionally, relationships between the basal forebrain volumes at baseline, risk of later cognitive decline, and scores on up-to 5 years of annual cognitive assessments were assessed with regression, survival analysis and linear mixed modelling. In patients, smaller volumes in a region corresponding to the nucleus basalis of Meynert were associated with greater change in global cognitive, but not motor, scores after 2 years. Using the binary classification procedure, patients classified as having smaller than expected volumes of the Nucleus Basalis of Meynert had ~3.5-fold greater risk of being categorised as mild cognitively impaired over up-to five years of follow up (HR = 3.51). Finally, linear mixed modelling analysis of domain-specific cognitive scores revealed that patients classified as having s

Regular sprint interval training (SIT) improves whole-body aerobic capacity and muscle oxidative potential, but very little is known about knee extensor anabolic or fatigue resistance adaptations, or whether effects are similar for males and females. The purpose of this study was to compare sex-related differences in knee extensor size, torque-velocity relationship and fatigability adaptations to 12 weeks SIT.Sixteen males and fifteen females (mean (SEM) age: 41 (±2.5) yrs) completed measurements of total body composition assessed by DXA, quadriceps muscle cross-sectional area (CSAQ) assessed by MRI, the knee extensor torque-velocity relationship (covering 0 - 240°·sec) and fatigue resistance, which was measured as the decline in torque from the first to the last of 60 repeated concentric knee extensions performed at 180°·sec. SIT consisted of 4 x 20 second sprints on a cycle ergometer set at an initial power output of 175% of power at VO2max, three times per week for 12 weeks.CSAQ increased by 5% (p=0.023) and fatigue resistance improved 4.8% (p=0.048), with no sex differences in these adaptations (sex comparisons: p=0.140 and p=0.282, respectively). Knee extensor isometric and concentric torque was unaffected by SIT in both males and females (p>0.05 for all velocities).12 weeks SIT, totalling 4 minutes very intense cycling per week, significantly increased fatigue resistance and CSAQ similarly in males and females, but did not significantly increase torque in males or females. These results suggest that SIT is a time-effective training modality for males and females to increase leg muscle size and fatigue resistance.

© 2017 International Osteoporosis Foundation and National Osteoporosis Foundation Summary: Bone mineral density declines with increasing older age. We examined the levels of circulating factors known to regulate bone metabolism in healthy young and older adults. The circulating levels of dickkopf-1, osteocalcin, osteoprotegerin and sclerostin were positively associated with whole-body bone mineral density (WBMD) in older adults, despite the average WBMD being lower and circulating dickkopf-1, osteoprotegerin and sclerostin being higher in old than young. Introduction: This study aims to investigate the relationship between whole-body bone mineral density (WBMD) and levels of circulating factors with known roles in bone remodelling during ‘healthy’ ageing. Methods: WBMD and fasting plasma concentrations of dickkopf-1, fibroblast growth factor-23, osteocalcin, osteoprotegerin, osteopontin and sclerostin were measured in 272 older subjects (69 to 81 years; 52% female) and 171 younger subjects (18–30 years; 53% female). Results: WBMD was lower in old than young. Circulating osteocalcin was lower in old compared with young, while dickkopf-1, osteoprotegerin and sclerostin were higher in old compared with young. These circulating factors were each positively associated with WBMD in the older adults and the relationships remained after adjustment for covariates (r values ranging from 0.174 to 0.254, all p < 0.01). In multivariate regression, the body mass index, circulating sclerostin and whole-body lean mass together accounted for 13.8% of the variation with WBMD in the older adults. In young adults, dickkopf-1 and body mass index together accounted for 7.7% of variation in WBMD. Conclusion: Circulating levels of dickkopf-1, osteocalcin, osteoprotegerin and sclerostin are positively associated with WBMD in community-dwelling older adults, despite the average WBMD being lower and circulating dickkopf-1, osteoprotegerin and sclerostin being higher in old than young.

Introduction: cognitive deterioration and reductions of bone health coincide with increasing age. We examine the relationship between bone composition and plasma markers of bone remodelling with measures of cognitive performance in healthy adults. Methods: this cross-sectional study included 225 old (52% women, mean age: 74.4 ± 3.3 years) and 134 young (52% women, mean age: 23.4 ± 2.7 years) adult participants from the MyoAge project. Whole body bone mineral density was measured by dualenergy X-ray absorptiometry. Blood analyses included a panel of bone-related peptides (dickkopf-1, osteoprotegerin, osteocalcin (OC), osteopontin, sclerostin, parathyroid hormone and fibroblast growth factor 23), as well as serum calcium and 25-hydroxy vitamin D assays. A selection of cognitive domains (working memory capacity, episodic memory, executive functioning and global cognition) was assessed with a standardised neuropsychological test battery. Results: adjusting for covariates and multiple testing revealed that plasma OC levels were positively associated with measures of executive functioning (β = 0.444, P < 0.001) and global cognition (β = 0.381, P = 0.001) in the older women. Discussion: these correlative results demonstrate a positive association between OC, a factor known to regulate bone remodelling, with cognitive performance in older non-demented women. Further work should address possible mechanistic interpretations in humans.

Adolescence is a period of significant brain plasticity that can be affected by environmental factors, including the degree of physical activity. Here we hypothesized that adolescent rats would be more sensitive to the beneficial metabolic and anti-inflammatory effects of voluntary exercise than adult rats, whose more mature brains have less capacity for plasticity. We tested this by giving adolescent and adult Wistar rats four weeks' voluntary access to running wheels. At the end of this period we assessed metabolic effects, including weight and circulating leptin and ghrelin, as well as performance in a novel object recognition test of memory and central changes in neuronal proliferation, survival, synaptic density, and inflammatory markers in hippocampus. We found exercise reduced fat mass and circulating leptin levels in both adults and adolescents but suppressed total weight gain and lean mass in adults only. Exercise stimulated neuronal proliferation in the suprapyramidal blade of the dentate gyrus in both adults and adolescents without altering the number of mature neurons during this time frame. Exercise also increased dentate microglial numbers in adolescents alone and microglial numbers in this region were inversely correlated with performance in the novel object recognition test. Together these data suggest that adolescent hippocampal microglia are more sensitive to the effects of exercise than those of adults, but this leads to no apparent improvement in recognition memory. This article is protected by copyright. All rights reserved.

Background The purpose of this study was to examine whether very short duration, very high intensity sprint interval training (SIT) leads to loss of body fat mass in association with improvements to VO2max and fatty acid oxidation, and to assess the extent of sex dimorphism in these physiological responses. Methods A total of 24 men and 17 women (mean (SEM) age: 39 (±2) years; body mass index 24.6 (0.6)) completed measurements of the maximal rate of oxygen uptake (VO2max) and fatty acid oxidation (FATmax). Body fat and lean mass were measured by dual emission x-ray absorptiometry, and fasting blood lipid, glucose and insulin profiles were assessed before and after training. SIT consisted of 4×20 s sprints on a cycle ergometer at approximately 175% VO2max, three times per week for 12 weeks. Results Fat mass decreased by 1.0 kg, although men lost statistically significantly more fat than women both when expressed in Kg and as % body fat. VO2max increased by around 9%, but women improved VO2max significantly more than men. FATmax improved by around 13%, but fasting plasma glucose, insulin, total triglyceride, total cholesterol and high-density lipoprotein (HDL) did not change after training, while low-density lipoprotein decreased by 8% (p=0.028) and the HDL:Total Cholesterol ratio improved by 6%. There were no sex differences in these metabolic responses to training. Conclusions These results show lower body fat %, and higher rates of fatty acid oxidation and VO2max after 12 weeks of training for just 4 min per week. Notably, women improved VO2max more than men, while men lost more fat than women.

Depression and anxiety can be severely detrimental to the health of both the affected woman and her offspring. In a rodent model of postpartum depression and anxiety, chronic social stress exposure during lactation induces deficits in maternal care and increases anxiety. Here, we extend previous findings by expanding the behavioral analyses, assessing lactation, and examining several neural systems within amygdalar and hypothalamic regions involved in the control of the stress response and expression of maternal care that may be mediating the behavioral changes in stressed dams. Compared with control dams, those exposed to chronic social stress beginning on day 2 of lactation show impaired maternal care and lactation and increased maternal anxiety on day 9 of lactation. Saccharin-based anhedonia and maternal aggression were increased and lactation was also impaired on day 16 of lactation. These behavioral changes were correlated with a decrease in oxytocin mRNA expression in the medial amygdala, and increases in the expressions of corticotrophin-releasing hormone mRNA in the central nucleus of the amygdala, glucocorticoid receptor mRNA in the paraventricular nucleus, and orexin 2 receptor mRNA in the supraoptic nucleus of stressed compared with control dams. The increase in glucocorticoid receptor mRNA in the paraventricular nucleus was negatively correlated with methylation of a CpG site in the promoter region. In conclusion, the data support the hypothesis that social stress during lactation can have profound effects on maternal care, lactation, and anxiety, and that these behavioral effects are mediated by central changes in stress and maternally relevant neuropeptide systems.

Angiosperms, http://name.umdl.umich.edu/IC-HERB00IC-X-1548429%5DMICH-V-1548429, https://quod.lib.umich.edu/cgi/i/image/api/thumb/herb00ic/1548429/MICH-V-1548429/!250,250, The University of Michigan Library provides access to these materials for educational and research purposes. Some materials may be protected by copyright. If you decide to use any of these materials, you are responsible for making your own legal assessment and securing any necessary permission. If you have questions about the collection, please contact the Herbarium professional staff: herb-dlps-help@umich.edu. If you have concerns about the inclusion of an item in this collection, please contact Library Information Technology: libraryit-info@umich.edu., https://www.lib.umich.edu/about-us/policies/copyright-policy