Dopamine D1 and Glutamate Receptors Co-operate With Brain-Derived Neurotrophic Factor (BDNF) and TrkB to Modulate ERK Signaling in Adult Striatal Slices

Abstract

In the striatum, the input nucleus of the basal ganglia, the extracellular-signal-regulated kinase (ERK) pathway, necessary for various forms of behavioral plasticity, is triggered by the combined engagement of dopamine D1 and ionotropic glutamate receptors. In this study, we investigated the potential crosstalk between glutamatergic, dopaminergic, and brain-derived neurotrophic factor (BDNF)-TrkB inputs to ERK cascade by using an ex vivo model of mouse striatal slices. Our results confirmed that the concomitant stimulation of D1 and glutamate receptors is necessary to activate ERK in striatal medium spiny neurons (MSNs). Moreover, we found that ERK activation is significantly enhanced when BDNF is co-applied either with glutamate or the D1 agonist SKF38393, supporting the idea of possible integration between BDNF, glutamate, and D1R-mediated signaling. Interestingly, ERK activation via BDNF-TrkB is upregulated upon blockade of either AMPAR/NMDAR or D1 receptors, suggesting a negative regulatory action of these two neurotransmitter systems on BDNF-mediated signaling. However, the observed enhancement of ERK1/2 phosphorylation does not result in corresponding downstream signaling changes at the nuclear level. Conversely, the TrkB antagonist cyclotraxin B partially prevents glutamate- and D1-mediated ERK activation. Altogether, these results suggest a complex and unexpected interaction among dopaminergic, glutamatergic, and BDNF receptor systems to modulate the ERK pathway in striatal neurons.

Dopamine Suppresses Osteogenic Differentiation of Rat Bone Marrow-Derived Mesenchymal Stem Cells via AKT/GSK-3β/β-Catenin Signaling Pathway

“…Third, DA might activate or inactivate different signaling pathways that lead to opposite effects. DA has been shown to exert biological effects through various signaling pathways including cAMP/PKA pathway, AKT/GSK-3 β pathway, Wnt/ β -catenin pathway, and ERK pathway [ 36 – 39 ]. It was found that DA could enhance the osteogenic differentiation of BMSCs by modulating the ERK signaling pathway [ 14 ], whereas our results showed that DA suppressed the osteogenic differentiation of rBMSCs by modulating the AKT/GSK-3 β / β -catenin signaling pathway.…”

Hyperoside Attenuate Inflammation in HT22 Cells via Upregulating SIRT1 to Activities Wnt/β-Catenin and Sonic Hedgehog Pathways

“…BDNF enhances neuronal survival and protects synaptic function by binding to tropomyosin receptor kinase B (TrkB) [ 33 , 34 ]. Simultaneously, BDNF promotes neuronal outward growth and recombination of dendritic spines, thereby improving neuronal connectivity [ 35 ]. NGF is a nerve cell growth regulator with dual biological functions of neuron nutrition and neurite outgrowth promotion.…”

Nicotine self-administration and ERK signaling are altered in RasGRF2 knockout mice

“…Previous studies have implicated ERK as a coincident detector of D1R-mediated signaling and NMDA receptor activation in the striatum critical to the regulation of drugdependent synaptic plasticity in the striatum (Zhang et al, 2004;Valjent et al, 2005;Jiao et al, 2007;Bertran-Gonzalez et al, 2008;Fasano et al, 2009;Ren et al, 2010;Morella et al, 2020). For example, both NMDA and D1 antagonists have been shown to block ERK phosphorylation in the striatum in response to a variety of drugs of abuse (Valjent et al, 2000;Valjent et al, 2004;Valjent et al, 2005).…”