by Keyword: Neuroprotection
Bravo, J, Ribeiro, I, Terceiro, AF, Andrade, EB, Portugal, CC, Lopes, IM, Azevedo, MM, Sousa, M, Lopes, CDF, Lobo, AC, Canedo, T, Relvas, JB, Summavielle, T, (2022). Neuron-Microglia Contact-Dependent Mechanisms Attenuate Methamphetamine-Induced Microglia Reactivity and Enhance Neuronal Plasticity Cells 11, 355
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.
JTD Keywords: cd200, contact-dependent, methamphetamine, neuron-to-microglia, psd95, Activation, Cd200, Contact-dependent, Expression, Glutamate, Methamphetamine, Neuron-to-microglia, Neuroprotection, Platform, Psd95
Gavín, Rosalina, Lidón, Laia, Ferrer, Isidre, del Río, José Antonio, (2020). The quest for cellular prion protein functions in the aged and neurodegenerating brain Cells 9, (3), 591
Cellular (also termed ‘natural’) prion protein has been extensively studied for many years for its pathogenic role in prionopathies after misfolding. However, neuroprotective properties of the protein have been demonstrated under various scenarios. In this line, the involvement of the cellular prion protein in neurodegenerative diseases other than prionopathies continues to be widely debated by the scientific community. In fact, studies on knock-out mice show a vast range of physiological functions for the protein that can be supported by its ability as a cell surface scaffold protein. In this review, we first summarize the most commonly described roles of cellular prion protein in neuroprotection, including antioxidant and antiapoptotic activities and modulation of glutamate receptors. Second, in light of recently described interaction between cellular prion protein and some amyloid misfolded proteins, we will also discuss the molecular mechanisms potentially involved in protection against neurodegeneration in pathologies such as Alzheimer’s, Parkinson’s, and Huntington’s diseases.
JTD Keywords: Prion, Tau, Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, Neuroprotection
Llorens, F., Del Rio, J. A., (2012). Unraveling the neuroprotective mechanisms of PrPC in excitotoxicity Prion , 6, (3), 245-251
Knowledge of the natural roles of cellular prion protein (PrPC) is essential to an understanding of the molecular basis of prion pathologies. This GPIanchored protein has been described in synaptic contacts, and loss of its synaptic function in complex systems may contribute to the synaptic loss and neuronal degeneration observed in prionopathy. In addition, Prnp knockout mice show enhanced susceptibility to several excitotoxic insults, GABAA receptor-mediated fast inhibition was weakened, LTP was modified and cellular stress increased. Although little is known about how PrPC exerts its function at the synapse or the downstream events leading to PrPCmediated neuroprotection against excitotoxic insults, PrPC has recently been reported to interact with two glutamate
receptor subunits (NR2D and GluR6/7). In both cases the presence of PrPC blocks the neurotoxicity induced by NMDA and Kainate respectively. Furthermore, signals for seizure and neuronal cell death in response to Kainate in Prnp knockout mouse are associated with JNK3 activity, through enhancing the interaction of GluR6 with PSD-95. In combination with previous data, these results shed light on the molecular mechanisms behind the role of PrPC in excitotoxicity. Future experimental approaches are suggested and discussed.
JTD Keywords: Prion protein, Excitotoxicity, Neuroprotection, Glutamate receptors, Synapse, prionopathy