Whole-body vibration ameliorates glial pathological changes in the hippocampus of hAPP transgenic mice, but does not affect plaque load

Abstract

Background Alzheimer’s disease (AD) is the core cause of dementia in elderly populations. One of the main hallmarks of AD is extracellular amyloid beta (Aβ) accumulation (APP-pathology) associated with glial-mediated neuroinflammation. Whole-Body Vibration (WBV) is a passive form of exercise, but its effects on AD pathology are still unknown. Methods Five months old male J20 mice (n = 26) and their wild type (WT) littermates (n = 24) were used to investigate the effect of WBV on amyloid pathology and the healthy brain. Both J20 and WT mice underwent WBV on a vibration platform or pseudo vibration treatment. The vibration intervention consisted of 2 WBV sessions of 10 min per day, five days per week for five consecutive weeks. After five weeks of WBV, the balance beam test was used to assess motor performance. Brain tissue was collected to quantify Aβ deposition and immunomarkers of astrocytes and microglia. Results J20 mice have a limited number of plaques at this relatively young age. Amyloid plaque load was not affected by WBV. Microglia activation based on IBA1-immunostaining was significantly increased in the J20 animals compared to the WT littermates, whereas CD68 expression was not significantly altered. WBV treatment was effective to ameliorate microglia activation based on morphology in both J20 and WT animals in the Dentate Gyrus, but not so in the other subregions. Furthermore, GFAP expression based on coverage was reduced in J20 pseudo-treated mice compared to the WT littermates and it was significantly reserved in the J20 WBV vs. pseudo-treated animals. Further, only for the WT animals a tendency of improved motor performance was observed in the WBV group compared to the pseudo vibration group. Conclusion In accordance with the literature, we detected an early plaque load, reduced GFAP expression and increased microglia activity in J20 mice at the age of ~ 6 months. Our findings indicate that WBV has beneficial effects on the early progression of brain pathology. WBV restored, above all, the morphology of GFAP positive astrocytes to the WT level that could be considered the non-pathological and hence “healthy” level. Next experiments need to be performed to determine whether WBV is also affective in J20 mice of older age or other AD mouse models.

Physical exercise regulates microglia in health and disease

“…In terms of specific microglial parameters, conflicting evidence exists regarding the impact of exercise on microglial numbers in AD mice. Some studies suggest that exercise leads to a decrease in microglial numbers ( Ke et al, 2011 ; Leem et al, 2011 ; Rodríguez et al, 2015 ; Wang Y. et al, 2023 ; Yang et al, 2023 ), while others indicate an increase ( Elahi et al, 2016 ; Xu et al, 2016 ; Hashiguchi et al, 2020 ; Zhang S. et al, 2022 ; Campos et al, 2023 ), and some findings show no significant change in microglial density in AD mice ( Xu et al, 2018 ; Zhang J. et al, 2018 ; Ziegler-Waldkirch et al, 2018 ; Oroszi et al, 2023 ). In terms of microglial phenotype, exercise can regulate CD68+ ( Ziegler-Waldkirch et al, 2018 ; Zhang S. et al, 2022 ; Oroszi et al, 2023 ; Wang Y. et al, 2023 ), CD86+ ( Lu et al, 2017 ; Zhang et al, 2019 ; Feng et al, 2023 ; Yang et al, 2023 ), triggering receptor expressed on myeloid cells 2 (TREM2) ( Zhang L. et al, 2022 ) and inflammatory molecules ( Xu et al, 2016 , 2018 ; Nakanishi et al, 2021 ; Han et al, 2023 ) in AD rodent models.…”

“…Some studies suggest that exercise leads to a decrease in microglial numbers ( Ke et al, 2011 ; Leem et al, 2011 ; Rodríguez et al, 2015 ; Wang Y. et al, 2023 ; Yang et al, 2023 ), while others indicate an increase ( Elahi et al, 2016 ; Xu et al, 2016 ; Hashiguchi et al, 2020 ; Zhang S. et al, 2022 ; Campos et al, 2023 ), and some findings show no significant change in microglial density in AD mice ( Xu et al, 2018 ; Zhang J. et al, 2018 ; Ziegler-Waldkirch et al, 2018 ; Oroszi et al, 2023 ). In terms of microglial phenotype, exercise can regulate CD68+ ( Ziegler-Waldkirch et al, 2018 ; Zhang S. et al, 2022 ; Oroszi et al, 2023 ; Wang Y. et al, 2023 ), CD86+ ( Lu et al, 2017 ; Zhang et al, 2019 ; Feng et al, 2023 ; Yang et al, 2023 ), triggering receptor expressed on myeloid cells 2 (TREM2) ( Zhang L. et al, 2022 ) and inflammatory molecules ( Xu et al, 2016 , 2018 ; Nakanishi et al, 2021 ; Han et al, 2023 ) in AD rodent models. Microglia morphology can also be regulated by physical exercise in AD mice, with most studies reporting that exercise reduces the numbers of reactive microglia and increases process ramification ( Ke et al, 2011 ; Leem et al, 2011 ; Xiong et al, 2015 ; Xu et al, 2016 ; Lu et al, 2017 ; Zhang S. et al, 2022 ; Feng et al, 2023 ; Oroszi et al, 2023 ).…”

“…In terms of microglial phenotype, exercise can regulate CD68+ ( Ziegler-Waldkirch et al, 2018 ; Zhang S. et al, 2022 ; Oroszi et al, 2023 ; Wang Y. et al, 2023 ), CD86+ ( Lu et al, 2017 ; Zhang et al, 2019 ; Feng et al, 2023 ; Yang et al, 2023 ), triggering receptor expressed on myeloid cells 2 (TREM2) ( Zhang L. et al, 2022 ) and inflammatory molecules ( Xu et al, 2016 , 2018 ; Nakanishi et al, 2021 ; Han et al, 2023 ) in AD rodent models. Microglia morphology can also be regulated by physical exercise in AD mice, with most studies reporting that exercise reduces the numbers of reactive microglia and increases process ramification ( Ke et al, 2011 ; Leem et al, 2011 ; Xiong et al, 2015 ; Xu et al, 2016 ; Lu et al, 2017 ; Zhang S. et al, 2022 ; Feng et al, 2023 ; Oroszi et al, 2023 ). However, one study utilizing 3XTg-AD mice, which exhibit plaque pathology and tau pathology at later stages, showed that 9 months of exercise increased hippocampal microglial hypertrophy (microglia surface, volume and somata volume) ( Rodríguez et al, 2015 ), indicating prolonged exercise may have differential regulatory effects compared to exercise of shorter durations.…”

Broadband vibroacoustic fingerprint of a historic building chamber concert room in Napoli (Italy)

“…In fact, airborne and ground-borne infra-sound vibrations with a frequency below 20 Hz can be perceived through human bodies, producing feelings of discomfort, which we often do not know how to rationally explain. On the other hand, sitting on the sand near the seashore, listening to the breaking of the waves or to the slow motion of the trees due to wind, produces feelings, often capable to generate an increased level of well-being in individuals, as proved by the positive results in using infrasound vibration therapy in the case of patients affected by neurodegenerative diseases [7,8]. This is why a previous study extended the domain of investigation of intangible cultural heritage to the vibroacoustic landscape [9], defined as the totality of mechanical vibrations generated by natural and anthropogenic sources, characterizing a certain place.…”