Endogenous TRPV1 expression in the human cingulate- and medial frontal gyrus

Background: The transient receptor potential vanilloid subtype-1 (TRPV1) channel is a calcium selective ion channel that responds to various stimuli such as heat, low pH, and capsaicin. Recently this channel was studied as an actuator for wireless neuromodulation in rodents, e.g., heat-induced activation of TRPV1 resulted in neuronal excitation. From a translational perspective, we addressed if TRPV1 is endogenously expressed in the human medial frontal gyms (MFG) and cingulate gyrus (CG) in depressed and control subjects and if it can be used as a means for neuromodulation in mood and other neuropsychiatric disorders.Methods: We assessed TRPV1 expression levels by Western blotting and evaluated its tissue and cellular distribution by means of immunohistochemistry.Results: TRPV1 was observed in all tissue samples, i.e., depressed and control, MFG and CG, yet the expression level as assessed by Western blotting varied between individuals. No intra-individual differences were seen between the MFG and CG. Immunohistochemistry showed that TRPV1 was expressed by glial-like cells but also in neurites, endothelial cells, and to a lesser extent in neuronal cell bodies. Fluorescent co-labeling of TRPV1 and glial fibrillary acidic protein (GFAP) identified most glial cells expressing TRPV1 to be astrocytes.Conclusion: These findings indicate that TRPV1 is endogenously expressed in the human CG and MFG. As TRPV1 is predominantly expressed by glial cells, this may suggest an opportunity for non-neuronal network modulation.