The air we breathe, the brain we have

Epidemiological studies put in evidence how the brain is emerging as an important target for adverse health effects of airborne pollutants (AP). We thus investigated the direct effect of AP on hCMEC/D3, astrocytes, microglia (MG) and neurons using the standard reference material of diesel exhaust particles (DEP). To study the DEP impact on purinergic signalling, we compared untreated primary MG with those incubated with DEP. Our data showed that DEP-activated MG generated much smaller ATP-induced Ca2+ waves, revealing a significant suppression of the receptor-evoked Ca2+ signals. The same results have been exactly replicated by hCMEC/D3. We then performed electrophysiological recordings in brain slices by means of Whole-Cell-Patch-Clamp on cortical pyramidal neurons. DEP induced a decrease of sEPSCs/sIPSCs frequency, indicating a pre-synaptic reduction of both excitatory and inhibitory neurotransmitter release. The overall outlined results stated that DEP induces Neuro-Vascular Unit dysfunctions. Finally, in light of our previous results related to the activities of multifunctional liposomes (mApoE-PA-LIP) we demonstrated the mApoE-PA-LIP induced rescue effects on DEP impaired synaptic functions. Our results clearly evidenced that DEP produces direct and indirect modifications on physiological mechanisms effectively linked to the onset and progression of neurodegenerative diseases, for which mApoE-PA-LIP could be promoted as innovative therapeutic tools.