Calorie restriction (CR) is neuroprotective in

The aims of this study were to evaluate the physical and chemical properties, cytotoxicity and dentinal tubule penetration of a new calcium silicate-based root canal dressing. For pH and calcium ion release evaluation (1, 24, 72 and 168 h) were used a pH meter and colorimetric spectrophotometer, respectively. Radiopacity evaluation followed the ISO 6876:2012. Cytotoxicity was evaluated by the percentage of cell viability using MTT assay. Illustrative images of dentinal tubule penetration were obtained using confocal laser scanning microscopy (CLSM). Data from pH and calcium ion release were statistically analyzed by two-way analysis of variance and Tukey test. Radiopacity was analyzed using the Student t-test. The statistical tests for cytotoxicity results were the one-way analysis of variance and Tukey test. Both materials showed alkaline pH in all experimental times. The pH values for calcium hydroxide paste were higher than bioceramic paste at 1, 24, and 72 h (p<0.05). The calcium ion release of bioceramic was lower than the calcium hydroxide paste only at 24 h (p<0.05). The bioceramic was more radiopaque than the calcium hydroxide paste (p<0.05). Bioceramic paste presented a dose and time-dependent cytotoxic effect after MTT assay. CLSM images showed absence of tubule penetration for both pastes. The new calcium silicate-based canal dressing presented alkaline pH, high calcium release, and acceptable radiopacity. Bio C Temp showed a dose and time-dependent cytotoxic and absence of dentinal tubule penetration.

The gut hormone ghrelin is widely beneficial in many disease states. However, ghrelin exists in two distinctive isoforms, each with its own metabolic profile. In Parkinson's Disease (PD) acylated ghrelin administration is neuroprotective, however, the role of des-acylated ghrelin remains unknown. In this study, we wanted to identify the relative contribution each isoform plays using the MPTP model of PD. Chronic administration of acylated ghrelin in mice lacking both isoforms of ghrelin (Ghrelin KO) attenuated the MPTP-induced loss on tyrosine hydroxylase (TH) neuronal number and volume and TH protein expression in the nigrostriatal pathway. Moreover, acylated ghrelin reduced the increase in glial fibrillary acidic protein and Ionized calcium binding adaptor molecule 1 microglia in the substantia nigra. However, injection of acylated ghrelin also elevated plasma des-acylated ghrelin, indicating in vivo deacetylation. Next, we chronically administered des-acylated ghrelin to Ghrelin KO mice and observed no neuroprotective effects in terms of TH cell number, TH protein expression, glial fibrillary acidic protein and ionized calcium binding adaptor molecule 1 cell number. The lack of a protective effect was mirrored in ghrelin-O-acyltransferase KO mice, which lack the ability to acylate ghrelin and consequently these mice have chronically increased plasma des-acyl ghrelin. Plasma corticosterone was elevated in ghrelin-O-acyltransferase KO mice and with des-acylated ghrelin administration. Overall, our studies suggest that acylated ghrelin is the isoform responsible for in vivo neuroprotection and that pharmacological approaches preventing plasma conversion from acyl ghrelin to des-acyl ghrelin may have clinical efficacy to help slow or prevent the debilitating effects of PD.

Summary Blood-borne factors regulate adult hippocampal neurogenesis and cognition in mammals. We report that elevating circulating unacylated-ghrelin (UAG), using both pharmacological and genetic methods, reduced hippocampal neurogenesis and plasticity in mice. Spatial memory impairments observed in ghrelin-O-acyl transferase-null (GOAT −/− ) mice that lack acyl-ghrelin (AG) but have high levels of UAG were rescued by acyl-ghrelin. Acyl-ghrelin-mediated neurogenesis in vitro was dependent on non-cell-autonomous BDNF signaling that was inhibited by UAG. These findings suggest that post-translational acylation of ghrelin is important to neurogenesis and memory in mice. To determine relevance in humans, we analyzed circulating AG:UAG in Parkinson disease (PD) patients diagnosed with dementia (PDD), cognitively intact PD patients, and controls. Notably, plasma AG:UAG was only reduced in PDD. Hippocampal ghrelin-receptor expression remained unchanged; however, GOAT + cell number was reduced in PDD. We identify UAG as a regulator of hippocampal-dependent plasticity and spatial memory and AG:UAG as a putative circulating diagnostic biomarker of dementia.