Age-associated bidirectional modulation of gene expression in single identified R15 neuron of Aplysia.

BACKGROUND: Despite the advances in our understanding of aging-associated behavioral decline, relatively little is known about how aging affects neural circuits that regulate specific behaviors, particularly the expression of genes in specific neural circuits during aging. We have addressed this by exploring a peptidergic neuron R15, an identified neuron of the marine snail Aplysia californica. R15 is implicated in reproduction and osmoregulation and responds to neurotransmitters such as acetylcholine, serotonin and glutamate and is characterized by its action potential bursts. RESULTS: We examined changes in gene expression in R15 neurons during aging by microarray analyses of RNAs from two different age groups, mature and old animals. Specifically we find that 1083 ESTs are differentially regulated in mature and old R15 neurons. Bioinformatics analyses of these genes have identified specific biological pathways that are up or downregulated in mature and old neurons. Comparison with human signaling networks using pathway analyses have identified three major networks [(1) cell signaling, cell morphology, and skeletal muscular system development (2) cell death and survival, cellular function maintenance and embryonic development and (3) neurological diseases, developmental and hereditary disorders] altered in old R15 neurons. Furthermore, qPCR analysis of single R15 neurons to quantify expression levels of candidate regulators involved in transcription (CREB1) and translation (S6K) showed that aging is associated with a decrease in expression of these regulators, and similar analysis in three other neurons (L7, L11 and R2) showed that gene expression change during aging could be bidirectional. CONCLUSIONS: We find that aging is associated with bidirectional changes in gene expression. Detailed bioinformatics analyses and human homolog searches have identified specific biological processes and human-relevant signaling pathways in R15 that are affected during aging. Evaluation of gene expression changes in different neurons suggests specific transcriptomic signature of single neurons during aging.

The effects of dietary silver on larval growth in the echinoderm Lytechinus variegatus.

Previous studies have demonstrated that the euryhaline copepod Acartia tonsa is extremely sensitive to dietborne silver (Ag) exposure, with a 20 % inhibition (EC(20)) of survival occurring when copepods are fed algae with 1.6 µg g(-1) dry weight (dw) Ag, corresponding to a waterborne Ag concentration of 0.46 µg l(-1) Ag. In contrast, 43 µg l(-1) Ag is required to elicit similar effects in copepods exposed to Ag by way of water. In the current study, we investigated whether another planktonic marine organism might also be sensitive to dietary Ag. Specifically, we tested larvae of the echinoderm, Lytechinus variegatus in an 18-day study in which larvae were continuously exposed to Ag-laden algae (Isochrysis galbana). After 7 days of exposure, no significant effects were observed on larval growth up to the highest concentration tested (10.68 µg g(-1) dw Ag in algae after exposure to 3.88 µg l(-1) waterborne Ag). After 18 days, significant effects were observed in all Ag treatments resulting in a lowest-observable effect concentration of 0.68 µg g(-1) dw Ag in algae and corresponding waterborne Ag concentration of 0.05-0.07 µg l(-1) Ag (depending on background Ag [see Results]). However, the dose-response relationship was quite flat with a similar level of growth inhibition (approximately 15 %) in all Ag treatments, resulting in an EC(20) of >10.68 µg g(-1) dw Ag in algae (>3.88 µg l(-1) Ag in water). This flat dose-response relationship is characteristic of dietary metal (silver, copper, cadmium, nickel, and zinc) toxicity to copepods as well, although the effect is slightly more robust (approximately 20-30 % inhibition of survival or reproduction). We conclude that echinoderm larvae may be similar to copepods in their sensitivity to dietary Ag, although a better understanding of the mechanisms underlying the apparent flat dose-response relationships is clearly needed.