Effects of Different Continuous Aerobic Training Protocols in a Heterozygous Mouse Model of Niemann-Pick Type C Disease

Abstract

The positive effects of physical activity on cognitive functions are widely known. Aerobic training is known to promote the expression of neurotrophins, thus inducing an increase in the development and survival of neurons, as well as enhancing synaptic plasticity. Based on this evidence, in the present study, we analyze the effects of two different types of aerobic training, progressive continuous (PC) and varying continuous (VC), on synaptic and muscular plasticity in heterozygous mice carrying the genetic mutation for Niemann-Pick type C disease. We also analyze the effects on synaptic plasticity by extracellular recordings in vitro in mouse hippocampal slices, while the morphological structure of muscle tissue was studied by transmission electron microscopy. Our results show a modulation of synaptic plasticity that varies according to the type of training protocol used, and only the VC protocol administered twice a week, has a significantly positive effect on long-term potentiation. On the contrary, ultrastructural analysis of muscle tissue shows an improvement in cellular conditions in all trained mice. These results confirm the beneficial effects of exercise on quality of life, supporting the hypothesis that physical activity could represent an alternative therapeutic strategy for patients with Niemann-Pick type C disease.

Neurodegeneration in Niemann–Pick Type C Disease: An Updated Review on Pharmacological and Non-Pharmacological Approaches to Counteract Brain and Cognitive Impairment

“…Since the UC protocol was not found to be effective in Npc1 +/− mice, probably because it was too weak and not demanding enough, we more recently evaluated the influence of exercise on neuroplasticity by subjecting Npc1 +/− mice to more challenging training protocols over a longer period [ 122 ]. Specifically, we administered two aerobic training protocols, progressive continuous (PC) and varying continuous (VC), which differed in terms of speed and velocity changes, as described previously [ 123 ] ( Table 1 ).…”

“…Both protocols had a total duration of 18 min. In addition, training sessions were conducted three times per week for twelve weeks (PCt and VCt, respectively) and, in the case of the VC protocol, also twice per week (VCb) [ 122 ]. Our results showed that the PCt protocol was not efficient enough as demonstrated by impairment in the LTP induction phase, whereas the VCt protocol was even more stressful and completely inhibited synaptic plasticity.…”

“…Our results showed that the PCt protocol was not efficient enough as demonstrated by impairment in the LTP induction phase, whereas the VCt protocol was even more stressful and completely inhibited synaptic plasticity. Surprisingly, the VCb protocol exerted a positive effect on LTP maintenance phase ( Figure 3 ), since we measured higher PS amplitude values in Npc1 +/− trained mice than in the control sedentary group [ 122 ].…”

“…Bars in the plot are means ± SEM of values obtained from different slices. Only the VCb protocol positively modulates synaptic plasticity, since the LTP maintenance phase was characterized by higher PS amplitude values compared with those in experimental groups (** p < 0.01) [ 122 ].…”

Dose–Response Effect of Vibratory Stimulus on Synaptic and Muscle Plasticity in a Middle-Aged Murine Model

“…One mm 3 of muscle tissue from left quadriceps biopsies were fixed in 4% paraformaldehyde and post-fixed in 2% osmium tetroxide (Cariati et al, 2020). After washing with 0.1 M phosphate buffer, the sample was dehydrated by a series of incubations in 30, 50, and 70% ethanol.…”