The Endocannabinoid,Anandamide, Augments Notch-1 Signaling in Cultured Cortical Neurons Exposed to Amyloid-β and in the Cortex of Aged Rats

Aberrant Notch signaling has recently emerged as a possible mechanism for the altered neurogenesis, cognitive impairment, and learning and memory deficits associated with Alzheimer disease (AD). Recently, targeting the endocannabinoid system in models of AD has emerged as a potential approach to slow the progression of the disease process. Although studies have identified neuroprotective roles for endocannabinoids, there is a paucity of information on modulation of the pro-survival Notch pathway by endocannabinoids. In this study the influence of the endocannabinoids, anandamide (AEA) and 2-arachidonoylglycerol, on the Notch-1 pathway and on its endogenous regulators were investigated in an in vitro model of AD. We report that AEA up-regulates Notch-1 signaling in cultured neurons. We also provide evidence that although Aβ_1–42 increases expression of the endogenous inhibitor of Notch-1, numb (Nb), this can be prevented by AEA and 2-arachidonoylglycerol. Interestingly, AEA up-regulated Nct expression, a component of γ-secretase, and this was found to play a crucial role in the enhanced Notch-1 signaling mediated by AEA. The stimulatory effects of AEA on Notch-1 signaling persisted in the presence of Aβ_1–42. AEA was found to induce a preferential processing of Notch-1 over amyloid precursor protein to generate Aβ_1–40. Aging, a natural process of neurodegeneration, was associated with a reduction in Notch-1 signaling in rat cortex and hippocampus, and this was restored with chronic treatment with URB 597. In summary, AEA has the proclivity to enhance Notch-1 signaling in an in vitro model of AD, which may have relevance for restoring neurogenesis and cognition in AD.     

Aging in the colonial chordate,Botryllus schlosseri

What mechanisms underlie aging? One theory, the wear-and-tear model, attributes aging to progressive deterioration in the molecular and cellular machinery which eventually lead to death through the disruption of physiological homeostasis. The second suggests that life span is genetically programmed, and aging may be derived from intrinsic processes which enforce a non-random, terminal time interval for the survivability of the organism. We are studying an organism that demonstrates both properties: the colonial ascidian, Botryllus schlosseri. Botryllus is a member of the Tunicata, the sister group to the vertebrates, and has a number of life history traits which make it an excellent model for studies on aging. First, Botryllus has a colonial life history, and grows by a process of asexual reproduction during which entire bodies, including all somatic and germline lineages, regenerate every week, resulting in a colony of genetically identical individuals. Second, previous studies of lifespan in genetically distinct Botryllus lineages suggest that a direct, heritable basis underlying mortality exists that is unlinked to reproductive effort and other life history traits. Here we will review recent efforts to take advantage of the unique life history traits of B. schlosseri and develop it into a robust model for aging research.     

The Quasi-Biennial Oscillation and Ross River virus incidence in Queensland,Australia

Ross River virus (RRV) is the most important vector-borne disease in Australia. The National Notifiable Diseases Surveillance System has confirmed that its incidence is often greatest in the state of Queensland, where there is a clear seasonal pattern as well as interannual variability. Previous studies have examined relationships between large-scale climate fluctuations (such as El Ni?o Southern Oscillation) and vector-borne disease. No previous study has examined such relationships with the Quasi-Biennial Oscillation (QBO), another large-scale climate fluctuation. We employ time-series analysis techniques to investigate cycles inherent in monthly RRV incidence in Queensland, Australia, from January 1991 to December 1997 inclusive. The presence of a quasi-biennial cycle in the RRV time series that is out of phase with the climatic QBO is described. Quantitative analyses using correlograms and periodograms demonstrate that the quasi-biennial cycle in the RRV time series is statistically significant, at the 95% level, above the noise. Together with the seasonal cycle, the quasi-biennial cycle accounts for 77% of the variance in Queensland RRV cases. Regression analysis of QBO and summer rainfall in three climatic zones of Queensland indicates a significant association between QBO and rainfall in the subtropical southeastern part of the state. These results suggest an indirect influence of the QBO on RRV incidence in Queensland, via its influence on climate in this region. Our findings indicate that the QBO may be a useful predictor of RRV at several months lead, and might be used by public health authorities in the management and prevention of this disease.