CALHM2 V136G polymorphism reduces astrocytic ATP release and is associated with depressive symptoms and Alzheimer's disease risk.

INTRODUCTION: Depression is considered a prodromal state of Alzheimer's disease (AD), yet the underlying mechanism(s) by which depression increases the risk of AD are not known. METHODS: Single-nucleotide polymorphism (SNP) analysis was used to determine the CALHM2 variants in AD patients. Cellular and molecular experiments were conducted to investigate the function of CALHM2 V136G mutation. We generated a new genetically engineered Calhm2 V136G mouse model and performed behavioral tests with these mice. RESULTS: CALHM2 V136G mutation (rs232660) is significantly associated with AD. V136G mutation resulted in loss of the CALHM2 ATP-release function in astrocytes and impaired synaptic plasticity. Mice homozygous for the Calhm2 V136G allele displayed depressive-like behaviors that were rescued by administration of exogenous ATP. Moreover, Calhm2 V136G mutation predisposed mice to cognitive decline in old age. DISCUSSION: CALHM2 dysfunction is a biologically relevant mechanism that may contribute to the observed clinical correlation between depression and AD.

[Isolation, identification, and degrading effect of a pyrene-degrading strain SE12].

Using pyrene as the sole carbon and energy source, and by the method of plate sublimation, a strain SE12 was isolated from a contaminated soil near Woniushan Coking Plant in Xuzhou, China. According to the morphological, biochemical, and 16S rDNA analyses, this strain was identified as Mycobacterium sp., with 98% of homology to the rapid-growth nonpathogenic strain M. austroafricanum ATCC 33464. The optimum pH and temperature for the degradation of pyrene by SE12 were pH 9 and 30 degrees C. When the soil samples were added with 100 and 200 mg x kg(-1) of pyrene and inoculated with 10(7) CFU x g(-1) of SE12, the degradation rates of pyrene reached to 97% and 99%, respectively after 28 days incubation at 30 degrees C. By using primer-pairs nidAF/nidAR and nidBF/nidBR for amplification of ring-hydroxylating dioxygenase genes, it was shown that SE12 had the fragments of encoded large and small subunits of dioxygenase genes. Sequence analysis showed that these fragments were highly homologous to the known dioxygenase genes from pyrene-degrading Mycobacteria sp.