Direct and indirect air pollution effects on synaptic neurotransmission linked to the development of neurodegenerative disease

In recent years, human epidemiological and animal studies show how the Central Nervous System (CNS) is emerging as an important target for adverse health effects of air pollution (AP), where they may be strongly associated with neurodegenerative disorders, such as Alzheimer’s disease (AD). Specifically, different studies demonstrate how exposure to AP induces synaptic plasticity impairment, both directly and indirectly. Our first aim is to investigate how AP modifies and invalidates delicate and complex mechanisms on which synaptic plasticity depends, including multiple neurotransmission signals, whose function is at the base of memory process. For this purpose, we exposed mouse brain slices to Diesel Exhaust Particles (DEP) (Reference Material), which constitute an important component of AP and can mimic its effects on CNS. We performed electrophysiological experiments through the Whole-Cell Patch Clamp technique on pyramidal neurons of the neocortex. DEP induce a widespread decrease of spontaneous Excitatory and Inhibitory Post Synaptic Currents (sEPSCs/sIPSCs) frequency with critical alterations on the pre-synaptic neurotransmitter release. Furthermore, we executed in vitro experiments through the Calcium Imaging technique on different neuronal support cells belonging to the Neurovascular Unit (NVU), which can modulate neurotransmission indirectly. DEP cause a strong decrease of the calcium wave response in different NVU cells. Hereafter, our second aim is based on preliminary results that highlight the effects of multifunctional liposomes (mApoE-PA-LIP) as a putative therapeutic tool for AD treatment. In particular, mApoE-PA-LIP can enhance NVU cells activity and ameliorate mouse model memory impairment. Thus, we tested the direct and indirect effects of mApoE-PA-LIP on synaptic transmission before and after DEP exposure with both ex vivo and in vitro experiments. In conclusion, AP produces significant direct and indirect modifications on physiological mechanisms of neurocommunication linked to the development of AD, for which mApoE-PA-LIP could be promoted as a strategy to counteract neurotransmission impairment.