Potassium channel gene associations with joint processing speed and white matter impairments in schizophrenia.

Patients with schizophrenia show decreased processing speed on neuropsychological testing and decreased white matter integrity as measured by diffusion tensor imaging, two traits shown to be both heritable and genetically associated indicating that there may be genes that influence both traits as well as schizophrenia disease risk. The potassium channel gene family is a reasonable candidate to harbor such a gene given the prominent role potassium channels play in the central nervous system in signal transduction, particularly in myelinated axons. We genotyped members of the large potassium channel gene family focusing on putatively functional single nucleotide polymorphisms (SNPs) in a population of 363 controls, 194 patients with schizophrenia spectrum disorder (SSD) and 28 patients with affective disorders with psychotic features who completed imaging and neuropsychological testing. We then performed three association analyses using three phenotypes - processing speed, whole-brain white matter fractional anisotropy (FA) and schizophrenia spectrum diagnosis. We extracted SNPs showing an association at a nominal P value of <0.05 with all three phenotypes in the expected direction: decreased processing speed, decreased FA and increased risk of SSD. A single SNP, rs8234, in the 3' untranslated region of voltage-gated potassium channel subfamily Q member 1 (KCNQ1) was identified. Rs8234 has been shown to affect KCNQ1 expression levels, and KCNQ1 levels have been shown to affect neuronal action potentials. This exploratory analysis provides preliminary data suggesting that KCNQ1 may contribute to the shared risk for diminished processing speed, diminished white mater integrity and increased risk of schizophrenia.

Brain gene expression changes elicited by peripheral vitellogenin knockdown in the honey bee.

Vitellogenin (Vg) is best known as a yolk protein precursor. Vg also functions to regulate behavioural maturation in adult honey bee workers, but the underlying molecular mechanisms by which it exerts this novel effect are largely unknown. We used abdominal vitellogenin (vg) knockdown with RNA interference (RNAi) and brain transcriptomic profiling to gain insights into how Vg influences honey bee behavioural maturation. We found that vg knockdown caused extensive gene expression changes in the bee brain, with much of this transcriptional response involving changes in central biological functions such as energy metabolism. vg knockdown targeted many of the same genes that show natural, maturation-related differences, but the direction of change for the genes in these two contrasts was not correlated. By contrast, vg knockdown targeted many of the same genes that are regulated by juvenile hormone (JH) and there was a significant correlation for the direction of change for the genes in these two contrasts. These results indicate that the tight coregulatory relationship that exists between JH and Vg in the regulation of honey bee behavioural maturation is manifest at the genomic level and suggest that these two physiological factors act through common pathways to regulate brain gene expression and behaviour.

Behavioral plasticity in honey bees is associated with differences in brain microRNA transcriptome.

Small, non-coding microRNAs (miRNAs) have been implicated in many biological processes, including the development of the nervous system. However, the roles of miRNAs in natural behavioral and neuronal plasticity are not well understood. To help address this we characterized the microRNA transcriptome in the adult worker honey bee head and investigated whether changes in microRNA expression levels in the brain are associated with division of labor among honey bees, a well-established model for socially regulated behavior. We determined that several miRNAs were downregulated in bees that specialize on brood care (nurses) relative to foragers. Additional experiments showed that this downregulation is dependent upon social context; it only occurred when nurse bees were in colonies that also contained foragers. Analyses of conservation patterns of brain-expressed miRNAs across Hymenoptera suggest a role for certain miRNAs in the evolution of the Aculeata, which includes all the eusocial hymenopteran species. Our results support the intriguing hypothesis that miRNAs are important regulators of social behavior at both developmental and evolutionary time scales.

Neuropeptide Y-like signalling and nutritionally mediated gene expression and behaviour in the honey bee.

Previous research has led to the idea that derived traits can arise through the evolution of novel roles for conserved genes. We explored whether neuropeptide Y (NPY)-like signalling, a conserved pathway that regulates food-related behaviour, is involved in a derived, nutritionally-related trait, the division of labour in worker honey bees. Transcripts encoding two NPY-like peptides were expressed in separate populations of brain neurosecretory cells, consistent with endocrine functions. NPY-related genes were upregulated in the brains of older foragers compared with younger bees performing brood care ('nurses'). A subset of these changes can be attributed to nutrition, but neuropeptide F peptide treatments did not influence sugar intake. These results contrast with recent reports of more robust associations between division of labour and the related insulin-signalling pathway and suggest that some elements of molecular pathways associated with feeding behaviour may be more evolutionarily labile than others.

Carbohydrate metabolism genes and pathways in insects: insights from the honey bee genome.

Carbohydrate-metabolizing enzymes may have particularly interesting roles in the honey bee, Apis mellifera, because this social insect has an extremely carbohydrate-rich diet, and nutrition plays important roles in caste determination and socially mediated behavioural plasticity. We annotated a total of 174 genes encoding carbohydrate-metabolizing enzymes and 28 genes encoding lipid-metabolizing enzymes, based on orthology to their counterparts in the fly, Drosophila melanogaster, and the mosquito, Anopheles gambiae. We found that the number of genes for carbohydrate metabolism appears to be more evolutionarily labile than for lipid metabolism. In particular, we identified striking changes in gene number or genomic organization for genes encoding glycolytic enzymes, cellulase, glucose oxidase and glucose dehydrogenases, glucose-methanol-choline (GMC) oxidoreductases, fucosyltransferases, and lysozymes.