Recent human and rodent brain imaging studies have shown that the shape of the brain can be changed by experience. These mesoscopic alterations in neuroanatomy are hypothesized to be driven by changes at the level of neuronal processes. To examine whether the shape of the brain changes rapidly, we used MRI to examine changes in the volume of the hippocampus across the 4-6 day estrous cycle in the female mouse. It is well known that changing steroid levels across the cycle influence dendritic spine maturation and alter synapse density in the hippocampus; our results show that the estrous cycle is associated with approximately 2-3% changes in hippocampal volume as seen by high-resolution ex-vivo MRI. Changes in hippocampal volume are, moreover, associated with a switch between hippocampal and striatal based navigation strategies in solving the dual choice T-maze in the same mice. A second experiment, using in-vivo MRI, suggests that these changes in hippocampal volume can occur over a 24 hour period. In summary, we show that the brain is highly plastic at a mesoscopic level of resolution detectable by MRI, that volumetric increases and decreases in hippocampal volume follow previously established patterns of changes in neuropil, and that these changes in volume predict changes in cognition.
With the most recent releases of the Drosophila melanogaster genome sequences, much of the previously absent heterochromatic sequences have now been annotated. We undertook an extensive genetic analysis of existing lethal mutations, as well as molecular mapping and sequence analysis (using a candidate gene approach) to identify as many essential genes as possible in the centromeric heterochromatin on the right arm of the second chromosome (2Rh) of D. melanogaster. We also utilized available RNA interference lines to knock down the expression of genes in 2Rh as another approach to identifying essential genes. In total, we verified the existence of eight novel essential loci in 2Rh: CG17665, CG17683, CG17684, CG17883, CG40127, CG41265, CG42595, and Atf6. Two of these essential loci, CG41265 and CG42595, are synonymous with the previously characterized loci l(2)41Ab and unextended, respectively. The genetic and molecular analysis of the previously reported locus, l(2)41Ae, revealed that this is not a single locus, but rather it is a large region of 2Rh that extends from unextended (CG42595) to CG17665 and includes four of the novel loci uncovered here.
Maternal diabetes and high-fat feeding during pregnancy have been linked to later life outcomes in offspring. To investigate the effects of both maternal and paternal hyperglycemia on offspring phenotypes, we utilized an autosomal dominant mouse model of diabetes (hypoinsulinemic hyperglycemia in Akita mice). We determined metabolic and skeletal phenotypes in wildtype offspring of Akita mothers and fathers.
Genome-wide association studies recently identified 32 loci that associate with the age at menarche (AAM) in humans. Because the locus most robustly associated with AAM is in/near LIN28B, the goal of this study was to investigate how the Lin28 pathway might modulate pubertal timing by examining expression of Lin28b, and its homologue, Lin28a, across the pubertal transition in female mice. Quantitative reverse-transcriptase PCR data indicate that, prior to the onset of puberty, expression of both Lin28b and Lin28a decreases in the ovary, while expression of only Lin28a decreases in the hypothalamus; the expression of Lin28a increases after the onset of puberty in the pituitary. Immunohistochemistry in ovarian tissue verified that Lin28a protein levels decreased in parallel with gene expression. Although these data do not demonstrate cause and effect, they do suggest that decreased expression of Lin28a/Lin28b may facilitate the transition into puberty, consistent with previous data showing that overexpression of Lin28a in transgenic mice leads to delayed puberty. In addition, although Lin28b and/or Lin28a expression significantly decreased prior to puberty, neither Let-7a nor Let-7g miRNA levels changed significantly, raising the possibility that some effects of Lin28b and Lin28a within the hypothalamic-pituitary-gonadal (HPG) axis may be Let-7 miRNA independent. Subsequent studies, such as tissue and age specific modulation of Lin28b and Lin28a expression, could determine whether the expression patterns observed are responsible for modulating the onset of puberty and delineate further the role of this pathway in the HPG axis.
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