Neuron-Microglia Contact-Dependent Mechanisms Attenuate Methamphetamine-Induced Microglia Reactivity and Enhance Neuronal Plasticity

• Type: Article in International Scientific Journal
• Date: 2022

Authors

Bravo, J (Author) Other; Ribeiro, I (Author) Other; Terceiro, AF (Author) Other; Andrade, EB (Author) Other; Portugal, CC (Author) Other; Lopes, IM (Author) Other; Azevedo, MM (Author) Other; Sousa, M (Author) Other; Lopes, CDF (Author) Other; Lobo, AC (Author) Other; Canedo, T (Author) Other; Relvas, JB (Author) FMUP; Summavielle, T (Author) Other

Journal

Title: Cells

Vol. 11

ISSN: 2073-4409

Publisher: MDPI

Indexing

ISI Web of Knowledge - 0 Citations

Scopus - 0 Citations

Other information

Authenticus ID: P-00W-624

DOI: 10.3390/cells11030355

Abstract (EN): Exposure to methamphetamine (Meth) has been classically associated with damage to neuronal terminals. However, it is now becoming clear that addiction may also result from the interplay between glial cells and neurons. Recently, we demonstrated that binge Meth administration promotes microgliosis and microglia pro-inflammation via astrocytic glutamate release in a TNF/IP(3)R2-Ca2+-dependent manner. Here, we investigated the contribution of neuronal cells to this process. As the crosstalk between microglia and neurons may occur by contact-dependent and/or contact-independent mechanisms, we developed co-cultures of primary neurons and microglia in microfluidic devices to investigate how their interaction affects Meth-induced microglia activation. Our results show that neurons exposed to Meth do not activate microglia in a cell-autonomous way but require astrocyte mediation. Importantly, we found that neurons can partially prevent Meth-induced microglia activation via astrocytes, which seems to be achieved by increasing arginase 1 expression and strengthening the CD200/CD200r pathway. We also observed an increase in synaptic individual area, as determined by co-localization of pre- and post-synaptic markers. The present study provides evidence that contact-dependent mechanisms between neurons and microglia can attenuate pro-inflammatory events such as Meth-induced microglia activation.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 17