Platinum nanoparticle-based microreactors protect against the behavioral and neurobiological consequences of chronic stress exposure

© 2022 Elsevier Inc. All rights reservedExcitotoxicity is described as the exacerbated activation of glutamate AMPA and NMDA receptors that leads to neuronal damage, and ultimately to cell death. Astrocytes are responsible for the clearance of 80-90% of synaptically released glutamate, preventing excitotoxicity. Chronic stress renders neurons vulnerable to excitotoxicity and has been associated to neuropsychiatric disorders, i.e., anxiety. Microreactors containing platinum nanoparticles (Pt-NP) and glutamate dehydrogenase have shown in vitro activity against excitotoxicity. The purpose of the present study was to investigate the in vivo effects of these microreactors on the behavioral and neurobiological effects of chronic stress exposure. Rats were either unstressed or exposed for 2 weeks to an unpredictable chronic mild stress paradigm (UCMS), administered intra-ventral hippocampus with the microreactors (with or without the blockage of astrocyte functioning), and seven days later tested in the elevated T-maze (ETM; Experiment 1). The ETM allows the measurement of two defensive responses, avoidance and escape, in terms of psychopathology respectively related to generalized anxiety and panic disorder. Locomotor activity in an open field was also measured. Since previous evidence shows that stress inhibits adult neurogenesis, we evaluated the effects of the different treatments on the number of cells expressing the marker of migrating neuroblasts doublecortin (DCX) in the dorsal and ventral hippocampus (Experiment 2). Results showed that UCMS induces anxiogenic effects, increases locomotion, and decreases the number of DCX cells in the dorsal and ventral hippocampus, effects that were counteracted by microreactor administration. This is the first study to demonstrate the in vivo efficacy of Pt-NP against the behavioral and neurobiological effects of chronic stress exposure.This study was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP, number 2019/26777-8), Coordenação de Aperfeiçoamento de Pessoal de Ensino Superior (CAPES PRINT 803269P), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação para a Ciência e para a Tecnologia (FCT) (PTDC/BTM-SAL/32147/2017), and 2020-WIDESPREAD-05-2017-Twinning (EpiEpinet) under grant agreement No. 952455.