Similar in vitro response of rat brain nerve terminals, colon preparations and COLO 205 cells to smoke particulate matter from different types of wood.

Major source of carbon-containing air born particular matter that significantly pollutes environment and provokes development of neuropathology is forest fires and wood combustion. Here, water-suspended smoke particulate matter preparations (SPs) were synthesized from birch, pine, poplar wood, and also birch bark and pine needles. Taking into account importance of the gut-brain communication system, SP properties were compared regarding their capability to modulate functioning of nerve terminals and gut cells/preparations. In cortex nerve terminals, poplar wood SP was more effective in decreasing uptake and increasing the extracellular levels of excitatory and inhibitory neurotransmitters L-[14C]glutamate and [3H]GABA, respectively. Spontaneous and H2O2-stimulated ROS generation in nerve terminals decreased by SPs, the most efficient one was from poplar wood. SPs from birch, pine and poplar wood caused membrane depolarization, poplar wood SP effect was 5-fold higher vs. birch and pine wood ones. Functional characteristics of gut cells/preparations, which tightly related to nerve terminal experiments, were assessed. SPs increased paracellular permeability of proximal colon mucosal-submucosal preparations monitored in Ussing chamber system (FITC-dextran, 4 kDa), where the most prominent effect had poplar wood SP. The latter demonstrated more considerable influence on COLO 205 cell causing 30 % loss of cell viability. PM emitted to the environment during combustion of various wood caused similar unidirectional harmful effects on brain and gut cell functioning, thereby triggering development of pathologies in gut and brain and gut-brain communication system.

Unique features of brain metastases-targeted AGuIX nanoparticles vs their constituents: A focus on glutamate-/GABA-ergic neurotransmission in cortex nerve terminals.

Gadolinium-based radiosensitizing AGuIX nanoparticles (AGuIX) currently tested two phase 2 clinical trials in association with radiotherapy for the treatment of brain metastases. Here, excitatory/inhibitory neurotransmission was assessed in rat cortex nerve terminals in the presence of AGuIX and their constituents (DOTAGA and DOTAGA/Gd3+) at concentrations used for medical treatment, and those 5-24 times higher. The ambient level, transporter-mediated, tonic and exocytotic release of L-[14C]glutamate and [3H]GABA, the membrane potential of nerve terminals were not changed in the presence of AGuIX at concentrations used for medical treatment ([Gd3+] = 0.25 mM, corresponding to 0.25 g.L-1), and DOTAGA (0.25 mM) and DOTAGA/Gd3+ (0.25 mM/0.01 mM). Difference between AGuIX and the precursors was uncovered, when their concentrations were increased. AGuIX (1.25-6 mM) did not change any transport characteristics of L-[14C]glutamate and [3H]GABA, whereas, DOTAGA (1.25-6 mM) affected the membrane potential, ambient level, and exocytotic release of L-[14C]glutamate and [3H]GABA. Gd3+ did not mask, but even enhanced above effects of DOTAGA. Therefore, AGuIX did not influence glutamate- and GABA-ergic neurotransmission at the presynaptic site. In contrast, DOTAGA and mixture DOTAGA/Gd3+ significantly affected synaptic neurotransmission at high concentrations. AGuIX own structure that overcomes neurotoxic features of their constituents.