Basal forebrain integrity and cognitive memory profile in healthy aging

Age-related dysfunctions in cholinergic and dopaminergic neuromodulation are assumed to contribute to age-associated impairment of explicit memory. Both neurotransmitters also modulate attention, working memory, and processing speed. To date, in vivo evidence linking structural age-related changes in these neuromodulatory systems to dysfunction within or across these cognitive domains remains scarce. Using a factor analytical approach in a cross-sectional study including 86 healthy older (aged 55 to 83 years) and 24 young (aged 18 to 30 years) adults, we assessed the relationship between structural integrity-as measured by magnetization transfer ratio (MTR)-of the substantia nigra/ventral tegmental area (SN/VTA), main origin of dopaminergic projections, basal forebrain (major origin of cortical cholinergic projections), frontal white matter (FWM), and hippocampus to neuro psychological and psychosocial scores. Basal forebrain MTR and FWM changes correlated with a factor combining verbal learning and memory and working memory and, as indicated by measures of diffusion, were most likely due to vascular pathology. These findings suggest that frontal white matter integrity and cholinergic neuromodulation provide clues as to why age-related cognitive decline is often correlated across cognitive domains. (C) 2009 Elsevier B.V. All rights reserved

MicroRNA-138 is a potential regulator of memory performance in humans

Genetic factors underlie a substantial proportion of individual differences in cognitive functions in humans, including processes related to episodic and working memory. While genetic association studies have proposed several candidate "memory genes," these currently explain only a minor fraction of the phenotypic variance. Here, we performed genome-wide screening on 13 episodic and working memory phenotypes in 1318 participants of the Berlin Aging Study II aged 60 years or older. The analyses highlight a number of novel single nucleotide polymorphisms (SNPs) associated with memory performance, including one located in a putative regulatory region of microRNA (miRNA) hsa-mir-138-5p (rs9882688, P-value = 7.8 x 10(-9)). Expression quantitative trait locus analyses on next-generation RNA-sequencing data revealed that rs9882688 genotypes show a significant correlation with the expression levels of this miRNA in 309 human lymphoblastoid cell lines (P-value = 5 x 10(-4)). In silico modeling of other top-ranking GWAS signals identified an additional memory-associated SNP in the 3' untranslated region (3' UTR) of DCP1B, a gene encoding a core component of the mRNA decapping complex in humans, predicted to interfere with hsa-mir-138-5p binding. This prediction was confirmed in vitro by luciferase assays showing differential binding of hsa-mir-138-5p to 3' UTR reporter constructs in two human cell lines (HEK293: P-value = 0.0470; SH-SY5Y: P-value = 0.0866). Finally, expression profiling of hsa-mir-138-5p and DCP1B mRNA in human post-mortem brain tissue revealed that both molecules are expressed simultaneously in frontal cortex and hippocampus, suggesting that the proposed interaction between hsa-mir-138-5p and DCP1B may also take place in vivo. In summary, by combining unbiased genome-wide screening with extensive in silico modeling, in vitro functional assays, and gene expression profiling, our study identified miRNA-138 as a potential molecular regulator of human memory function

Heterothermy and seasonal patterns of metabolic rate in the southern African hedgehog (Atelerix frontalis)

Animals that inhabit unfavourable habitats and experience seasons where the cost of maintenance exceeds the available energy resources have over time developed behavioural and physiological mechanisms to survive. These adaptations include changes in activity, improvement of cold tolerance by using nonshivering thermogenesis (NST), improvement of thermal conductance, reduction of body mass, or acclimation to colder temperatures (reduction of metabolic requirement). In addition some species exhibit heterothermy, in the form of either daily torpor or longer-term hibernation. The southern African hedgehog (Atelerix frontalis) is an excellent candidate to investigate the phenomenon of heterothermy because it is a small insectivore (summer body mass ca. 300 to 400g), burrows, inhabits harsh habitats and is not easy to find during the winter months. In this study I aimed to investigate whether A. frontalis exhibits seasonal differences in metabolic rate and furthermore if this species exhibits heterothermy. The study was carried out in the Northern Cape Province, South Africa. Hedgehogs were hand captured and their metabolic rates were measured using indirect calorimetry. Individuals were implanted with temperature dataloggers for a summer period (November 2009-January 2010) and a winter period (May-August 2009). The summer BMR of adult A. frontalis (0.448 ±0.035 mlO2/g/h, n=4) was significantly lower than their winter BMR (0.811 ±0.073 mlO2/g/h, n=4) and statistical analyses revealed that this was an affect caused by seasonal changes in the ambient environment. Individuals spent up to 84 percent of time during the measurement period torpid (-8°C <Ta<21°C). Body mass appears to be an important factor in determining the pattern of heterothermy (daily torpor versus hibernation) used in this species. To my knowledge the extremely low body temperature (Tb min) of 1.0°C recorded for A. frontalis is the lowest Tb min recorded for a mainland Afrotropical mammal. This species displays classic up-regulation in metabolic rate during winter, resulting in an increase in the energetic requirements of the species. As a result, heterothermy appears to play a significant role in the energy balance of this species during winter, contributing to energy saving. Heterothermy may enable this species to survive in the face of global climate change