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Daskalakis, E.

Publications and source records attributed to Daskalakis, E..

2 recordsLinked to original sources

Elevated body mass index in youth is associated with dysregulated surrogate markers of neural inhibition & excitation, and internetwork functional dysconnectivity

The developing child and adolescent brain is thought to have an increased vulnerability to the negative impact of obesity and excessive consumption of hyperpalatable and energy-rich foods. In this study, we investigated the neurophysiological effects of overweight and obesity in 30 participants spanning childhood and adolescence (8-19 years), using a naturalistic viewing paradigm with Inscapes, in a pseudo-resting-state protocol scan with magnetoencephalography (MEG). Subjects were median split on body mass indices (BMI), categorised into two groups comprising: lower <25 kg/m2 (n=15) and higher [&ge;]25 kg/m2 (n=15). We assessed spontaneous, regional neural function indexed by oscillatory activity, and functional connectivity within and between intrinsic resting brain networks, including the default mode network, dorsal and ventral attention, somatomotor, visual, language, central executive and salience networks. Elevated BMI was associated with significant reductions in activity of the posterior dominant rhythm, and gamma hyperactivity across widespread cortical areas, suggesting intrinsic neuronal hyperexcitability and disinhibition in children and adolescents. Additionally, we observed low-frequency theta hypoconnectivity between resting state networks including the salience, visual, and default mode networks, and overall reduced global efficiency in brain network structure, suggesting reduced effectiveness in neural communication. These findings underscore the neural impact of body composition on the developing brain, suggesting deleterious alterations in excitation and inhibition from surrogate neural markers associated with neurochemistry and brain networks linked with cognitive and behavioural functioning. These alterations may contribute to the persistent behavioural rigidity and difficulties in adopting healthier eating behaviours into adulthood.

neuroscience↗

Oral pyruvate prevents glaucomatous neurodegeneration

Intraocular pressure-sensitive retinal ganglion cell degeneration is a hallmark of glaucoma, the leading cause of irreversible blindness. Converging evidence indicates that age-related bioenergetic insufficiency increases the vulnerability of retinal ganglion cells to intraocular pressure. To investigate further, we used metabolomics and RNA-sequencing to examine early glaucoma in DBA/2J mice. We demonstrate an intraocular pressure-dependent decline in retinal pyruvate levels coupled to dysregulated glucose metabolism prior to detectable optic nerve degeneration. Oral supplementation of pyruvate strongly protected from neurodegeneration in pre-clinical models of glaucoma. We detected mTOR activation at the mechanistic nexus of neurodegeneration and metabolism. Rapamycin-induced inhibition of mTOR robustly prevented glaucomatous neurodegeneration. Bioenergetic enhancement, in combination with intraocular pressure reduction, therefore provides a readily translatable strategy that warrants investigation in clinical trials. FundingVetenskapsr[a]det 2018-02124 and StratNeuro StartUp grant (PAW). Pete Williams is supported by the Karolinska Institutet in the form of a Board of Research Faculty Funded Career Position and by St. Erik Eye Hospital philanthropic donations. EY011721 and the Barbra and Joseph Cohen Foundation and startup funds from Columbia University (SWMJ). Simon John is an Investigator of HHMI.

neuroscience↗