Biology subjects

Sensi, S. L.

Publications and source records attributed to Sensi, S. L..

3 recordsLinked to original sources

bioRxiv2018

Elevated plasma ceramide levels in post-menopausal women

Circulating ceramide levels are abnormally elevated in age-dependent pathologies such as cardiovascular diseases, obesity and Alzheimers disease. Nevertheless, the potential impact of age on plasma ceramide levels has not yet been systematically examined. In the present study, we quantified a focused panel of plasma ceramides and dihydroceramides in a cohort of 164 subjects (84 women) 19 to 80 years of age. After adjusting for potential confounders, multivariable linear regression analysis revealed a positive association between age and ceramide (d18:1/24:0) ({beta} (SE) = 5.67 (2.38); p = .0198) and ceramide (d18:1/24:1) ({beta} (SE) = 2.88 (.61); p < .001) in women, and between age and ceramide (d18:1/24:1) in men ({beta} (SE) = 1.86 (.77); p = .0179). In women of all ages, but not men, plasma ceramide (d18:1/24:1) was negatively correlated with plasma estradiol (r = -0.294; p = .007). Finally, in vitro experiments in human cancer cells expressing estrogen receptors showed that incubation with estradiol (10 nM, 24 h) significantly decreased ceramide accumulation. Together, the results suggest that aging is associated with an increase in circulating ceramide levels, which in post-menopausal women may be at least partially dependent on lower estradiol levels.

biochemistry↗

bioRxiv2018

Functional signature of conversion in Mild Cognitive Impairment patients

The entorhinal-hippocampal circuit is a strategic hub for memory but also the first site to be affected in the Alzheimers Disease (AD)-related pathology. We investigated MRI patterns of brain atrophy and functional connectivity in a study cohort obtained from the Alzheimers Disease Neuroimaging Initiative database including healthy control (HC), Mild Cognitive Impairment (MCI), and AD subjects. MCI individuals were clinically evaluated 24 months after the MRI scan, and the group further divided into a subset of subjects who either did (c-MCI) or did not (nc-MCI) convert to AD. Compared to HC subjects, AD patients exhibited a collapse of long-range connectivity from the hippocampus and entorhinal cortex, pronounced cortical/sub-cortical atrophy, and a dramatic decline in cognitive performances. c-MCI patients showed entorhinal and hippocampal hypo-connectivity, no signs of cortical thinning but evidence of right hippocampus atrophy. On the contrary, nc-MCI patients showed lack of brain atrophy, largely preserved cognitive functions, hippocampal and entorhinal hyper-connectivity with selected neocortical/sub-cortical regions mainly involved in memory processing and brain meta-stability. This hyper-connectivity can represent an early compensatory strategy to overcome the progression of cognitive impairment. This functional signature can also be employed for the diagnosis of c-MCI subjects.

neuroscience↗

bioRxiv2018

The pharmacological perturbation of brain zinc impairs BDNF-related signalling and the cognitive performances of young mice

Zinc (Zn2+) is a pleiotropic modulator of the neuronal and brain activity. The disruption of intraneuronal Zn2+ levels triggers neurotoxic processes and affects neuronal functioning. In this study, we investigated how the pharmacological modulation of brain Zn2+ affects synaptic plasticity and cognition in wild-type mice. To manipulate brain Zn2+ levels, we employed the Zn2+ (and copper) chelator 5-chloro-7-iodo-8-hydroxyquinoline (clioquinol, CQ). CQ was administered for two weeks to 2.5-month-old (m.o.) mice, and effects studied on BDNF-related signalling, metalloproteinase activity as well as learning and memory performances. CQ treatment was found to negatively affect short- and long-term memory performances. The CQ-driven perturbation of brain Zn2+ was found to reduce levels of BDNF, synaptic plasticity-related proteins and dendritic spine density in vivo.\n\nOur study highlights the importance of choosing \"when\", \"where\", and \"how much\" in the modulation of brain Zn2+ levels. Our findings confirm the importance of targeting Zn2+ as a therapeutic approach against neurodegenerative conditions but, at the same time, underscore the potential drawbacks of reducing brain Zn2+ availability upon the early stages of development.

neuroscience↗