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Aprinda Indahlastari,1,2 Cheshire Hardcastle,1,2 Alejandro Albizu,1,3 Stacey Alvarez-Alvarado,1,2 Emanuel M Boutzoukas,1,2 Nicole D Evangelista,1,2 Hanna K Hausman,1,2 Jessica Kraft,1,3 Kailey Langer,1,2 Adam J Woods1– 3 1Center for Cognitive Aging and Memory, McKnight Brain Institute, University of Florida, Gainesville, FL, USA; 2Department of Clinical and Health Psychology, University of Florida, Gainesville, FL, USA; 3Department of Neuroscience, University of Florida, Gainesville, FL, USACorrespondence: Aprinda IndahlastariDepartment of Clinical and Health Psychology, University of Florida, Gainesville, FL, USATel +1 352-294-5842Email aprinda.indahlas@phhp.ufl.eduBackground: Transcranial direct current stimulation (tDCS) has been proposed as a possible method for remediating age-associated cognitive decline in the older adult population. While tDCS has shown potential for improving cognitive functions in healthy older adults, stimulation outcomes on various cognitive domains have been mixed.Methods: A systematic search was performed in four databases: PubMed, EMBASE, Web of Science, and PsychInfo. Search results were then screened for eligibility based on inclusion/exclusion criteria to only include studies where tDCS was applied to improve cognition in healthy older adults 65 years and above. Eligible studies were reviewed and demographic characteristics, tDCS dose parameters, study procedures, and cognitive outcomes were extracted. Reported effect sizes for active compared to sham group in representative cognitive domain were converted to Hedges’ g.Main Results: A total of thirteen studies involving healthy older adults (n=532, mean age=71.2+ 5.3 years) were included in the meta-analysis. The majority of included studies (94%) targeted the prefrontal cortex with stimulation intensity 1– 2 mA using various electrode placements with anodes near the frontal region. Across all studies, we found Hedges’ g values ranged from − 0.31 to 1.85 as reported group effect sizes of active stimulation compared to sham.Conclusion: While observed outcomes varied, overall findings indicated promising effects of tDCS to remediate cognitive aging and thus deserves further exploration. Future characterization of inter-individual variability in tDCS dose response and applications in larger cohorts are warranted to further validate benefits of tDCS for cognition in healthy older adults.Keywords: tES, tDCS, aging, cognitive decline

Dominik Gonnissen,1 Ying Qu,1,2 Klaus Langer,3 Cengiz Öztürk,4 Yuliang Zhao,2 Chunying Chen,2 Guiscard Seebohm,5 Martina Düfer,6 Harald Fuchs,1 Hans-Joachim Galla,7 Kristina Riehemann11Center for Nanotechnology, Institute of Physics, University of Münster, Münster, Germany; 2National Center for Nanoscience and Technology, Chinese Academy of Sciences, Beijing, People’s Republic of China; 3Institute of Pharmaceutical Technology and Biopharmacy, University of Münster, Münster, 4chemicell GmbH, Berlin, 5Department of Cardiovascular Medicine, Institute for Genetics of Heart Diseases, University Hospital Münster, 6Department of Pharmacology, Institute of Pharmaceutical and Medicinal Chemistry, 7Department of Cell Biology/Biophysics, Institute of Biochemistry, University of Münster, Münster, GermanyAbstract: Within the last years, progress has been made in the knowledge of the properties of medically used nanoparticles and their toxic effects, but still, little is known about their influence on cellular processes of immune cells. The aim of our comparative study was to present the influence of two different nanoparticle types on subcellular processes of primary monocytes and the leukemic monocyte cell line MM6. We used core-shell starch-coated superparamagnetic iron oxide nanoparticles (SPIONs) and matrix poly(lactic-co-glycolic acid) (PLGA) nanoparticles for our experiments. In addition to typical biocompatibility testing like the detection of necrosis or secretion of interleukins (ILs), we investigated the impact of these nanoparticles on the actin cytoskeleton and the two voltage-gated potassium channels Kv1.3 and Kv7.1. Induction of necrosis was not seen for PLGA nanoparticles and SPIONs in primary monocytes and MM6 cells. Likewise, no alteration in secretion of IL-1β and IL-10 was detected under the same experimental conditions. In contrast, IL-6 secretion was exclusively downregulated in primary monocytes after contact with both nanoparticles. Two-electrode voltage clamp experiments revealed that both nanoparticles reduce currents of the aforementioned potassium channels. The two nanoparticles differed significantly in their impact on the actin cytoskeleton, demonstrated via atomic force microscopy elasticity measurement and phalloidin staining. While SPIONs led to the disruption of the respective cytoskeleton, PLGA did not show any influence in both experimental setups. The difference in the effects on ion channels and the actin cytoskeleton suggests that nanoparticles affect these subcellular components via different pathways. Our data indicate that the alteration of the cytoskeleton and the effect on ion channels are new parameters that describe the influence of nanoparticles on cells. The results are highly relevant for medical application and further evaluation of nanomaterial biosafety. Keywords: actin cytoskeleton, cell elasticity, AFM, ion channels, patch clamp, TEVC