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, 2016, 1568145

Perspectives of TRPV1 Function on the Neurogenesis and Neural Plasticity


Perspectives of TRPV1 Function on the Neurogenesis and Neural Plasticity

R Ramírez-Barrantes et al. Neural Plast.


The development of new strategies to renew and repair neuronal networks using neural plasticity induced by stem cell graft could enable new therapies to cure diseases that were considered lethal until now. In adequate microenvironment a neuronal progenitor must receive molecular signal of a specific cellular context to determine fate, differentiation, and location. TRPV1, a nonselective calcium channel, is expressed in neurogenic regions of the brain like the subgranular zone of the hippocampal dentate gyrus and the telencephalic subventricular zone, being valuable for neural differentiation and neural plasticity. Current data show that TRPV1 is involved in several neuronal functions as cytoskeleton dynamics, cell migration, survival, and regeneration of injured neurons, incorporating several stimuli in neurogenesis and network integration. The function of TRPV1 in the brain is under intensive investigation, due to multiple places where it has been detected and its sensitivity for different chemical and physical agonists, and a new role of TRPV1 in brain function is now emerging as a molecular tool for survival and control of neural stem cells.


Figure 1
Figure 1
Diagram of regions involved in TRPV1 function. (a) The primary structure involves six transmembrane segments (S1–S6) with a pore domain between the fifth (S5) and sixth (S6) segment, and both C and N termini are located intracellularly. The functional TRPV1 receptor is believed to form a homotetramer. Amino acid residues involved in the binding of chemical and physical activation/modulation of TRPV1 activity are indicated in a color scheme. Vanilloid compounds, as the activators capsaicin and resiniferatoxin, as well as inhibitor capsazepine share the same binding site, while cholesterol-binding site is composed of a promiscuous hydrophobic pocket in S5. (b) Model for hydrophobic pocket in S5 linker with the binding of lipidic molecules such as cholesterol (chol), PIP2, and capsaicin (CAP) generated by molecular dynamics. In this binding conformation, all the molecules occupy a groove formed between S5 and C-terminal of the subunit.
Figure 2
Figure 2
TRPV1 detected by immunofluorescence. (a) Methodology proposed for detection of TRPV1 by immunofluorescence. Using two antibodies against different epitopes of the channel allows corroborating the expression of the channel. In this case, we showed an antibody against the C-terminal and another against the N-terminal. As both antibodies bind to intracellular epitopes, it is advisable to use as internal control of the technique a sample without permeabilization of the plasma membrane, which prevents the entry of the antibody into the cell. One added strategy to improve signal sensitivity was the use of a blocking peptide, in this case, for the C-terminal or N-terminal. The competition of the blocking peptide with the epitope of the channel should diminish the intensity of the signal indicating the specificity of the technique. (b) Detection of TRPV1 in heterologous expression system using antibodies against the N-terminal and C-terminal of TRPV1. (c) Detection of TRPV1 in primate prefrontal cortex, using an antibody against the N-terminal and another against the C-terminal.
Figure 3
Figure 3
Expression of TRPV1 in neuronal differentiation process derived from LYON-ES. Determination of expression of TRPV1 by immunofluorescence staining for undifferentiated monkey ESCs stably expressing Tau-GFP (TAU-GFP LYON-ES1 line, a–d), NSCs (NS, e–h), neurons (i–l), and glial cells (m–p) derived from TAU-GFP-LYON-ES1 cells. At each stage, we performed immunofluorescence with antibodies against Oct4 (c) to identify LYON-ESCs, Pax6 for NSCs (g), β-III-tubulin for neurons (k), glial fibrillary acid protein (GFAP) for glial cells (o), and TRPV1 (d, h, l, p). Each experiment was accompanied by nuclear staining with DAPI (a, e, i, m), all the cells having a GFP fused to the microtubule-associated protein tau (b, f, j, n). The magnification of images was 20x for LYON-ESCs and neurons, and 40x for NSCs and glia cells.

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