Abstract
Transient receptor potential vanilloid type-1 (TRPV1) is a ligand-gated nonselective cation channel that has been well characterized in peripheral pain pathway. Recent evidence from animal models of temporal lobe epilepsy (TLE) has supported the important role of TRPV1 in epileptogenesis. In this study, we investigated the expression and cellular distribution of TRPV1 in the temporal cortex (CTX) and hippocampus (HPC) from 26 patients with mesial TLE (MTLE) compared with 12 histologically normal samples. Reverse transcription-PCR and Western blotting revealed up-regulated mRNA and protein levels of TRPV1 in the MTLE group versus the control group. Immunohistochemistry data demonstrated that TRPV1 was mainly distributed in the cell bodies and dendrites of neurons. Double-labeled immunofluorescence further revealed that TRPV1 was localized on NeuN-positive neurons and GFAP-positive astrocytes, but not on HLA-positive microglia. In addition, its co-localization with glutamate and gamma-aminobutyric acid (GABA) indicated that TRPV1 was distributed on both glutamatergic and GABAergic neurons. Moreover, nerve growth factor, a sensitizing factor for TRPV1, was showed a higher expression pattern in MTLE patients. Taken together, our findings suggest that the overexpression and distribution patterns of TRPV1 might be involved in the pathogenesis and epileptogenesis of human MTLE.
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References
Adams B, Sazgar M, Osehobo P et al (1997) Nerve growth factor accelerates seizure development, enhances mossy fiber sprouting, and attenuates seizure-induced decreases in neuronal density in the kindling model of epilepsy. J Neurosci 17(14):5288–5296
Al-Hayani A, Wease KN, Ross RA, Pertwee RG, Davies SN (2001) The endogenous cannabinoid anandamide activates vanilloid receptors in the rat hippocampal slice. Neuropharmacology 41(8):1000–1005
Amaya F, Shimosato G, Nagano M et al (2004) NGF and GDNF differentially regulate TRPV1 expression that contributes to development of inflammatory thermal hyperalgesia. Eur J Neurosci 20(9):2303–2310
Bae EK, Jung KH, Chu K et al (2010) Neuropathologic and clinical features of human medial temporal lobe epilepsy. J Clin Neurol 6(2):73–80
Bhaskaran MD, Smith BN (2010) Effects of TRPV1 activation on synaptic excitation in the dentate gyrus of a mouse model of temporal lobe epilepsy. Exp Neurol 223(2):529–536
Blumcke I, Pauli E, Clusmann H et al (2007) A new clinico-pathological classification system for mesial temporal sclerosis. Acta Neuropathol 113(3):235–244
Caterina MJ, Schumacher MA, Tominaga M, Rosen TA, Levine JD, Julius D (1997) The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature 389(6653):816–824
Caterina MJ, Rosen TA, Tominaga M, Brake AJ, Julius D (1999) A capsaicin-receptor homologue with a high threshold for noxious heat. Nature 398(6726):436–441
Cavus I, Kasoff WS, Cassaday MP et al (2005) Extracellular metabolites in the cortex and hippocampus of epileptic patients. Ann Neurol 57(2):226–235
Chabardes S, Kahane P, Minotti L et al (2005) The temporopolar cortex plays a pivotal role in temporal lobe seizures. Brain 128(Pt 8):1818–1831
Clement AB, Hawkins EG, Lichtman AH, Cravatt BF (2003) Increased seizure susceptibility and proconvulsant activity of anandamide in mice lacking fatty acid amide hydrolase. J Neurosci 23(9):3916–3923
Davies JW, Hainsworth AH, Guerin CJ, Lambert DG (2010) Pharmacology of capsaicin-, anandamide-, and N-arachidonoyl-dopamine-evoked cell death in a homogeneous transient receptor potential vanilloid subtype 1 receptor population. Br J Anaesth 104(5):596–602
Davis JB, Gray J, Gunthorpe MJ et al (2000) Vanilloid receptor-1 is essential for inflammatory thermal hyperalgesia. Nature 405(6783):183–187
Devane WA, Hanus L, Breuer A et al (1992) Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science 258(5090):1946–1949
During MJ, Spencer DD (1993) Extracellular hippocampal glutamate and spontaneous seizure in the conscious human brain. Lancet 341(8861):1607–1610
Ermolinsky BS, Skinner F, Garcia I et al (2011) Upregulation of STREX splice variant of the large conductance Ca2+-activated potassium (BK) channel in a rat model of mesial temporal lobe epilepsy. Neurosci Res 69(1):73–80
Fu M, Xie Z, Zuo H (2009) TRPV1: a potential target for antiepileptogenesis. Med Hypotheses 73(1):100–102
Gibson HE, Edwards JG, Page RS, Van Hook MJ, Kauer JA (2008) TRPV1 channels mediate long-term depression at synapses on hippocampal interneurons. Neuron 57(5):746–759
Ji RR, Samad TA, Jin SX, Schmoll R, Woolf CJ (2002) p38 MAPK activation by NGF in primary sensory neurons after inflammation increases TRPV1 levels and maintains heat hyperalgesia. Neuron 36(1):57–68
Karlsson U, Sundgren-Andersson AK, Johansson S, Krupp JJ (2005) Capsaicin augments synaptic transmission in the rat medial preoptic nucleus. Brain Res 1043(1–2):1–11
Kauer JA, Gibson HE (2009) Hot flash: TRPV channels in the brain. Trends Neurosci 32(4):215–224
Kim SR, Bok E, Chung YC, Chung ES, Jin BK (2008) Interactions between CB(1) receptors and TRPV1 channels mediated by 12-HPETE are cytotoxic to mesencephalic dopaminergic neurons. Br J Pharmacol 155(2):253–264
Langlois M, Polack PO, Bernard H et al (2010) Involvement of the thalamic parafascicular nucleus in mesial temporal lobe epilepsy. J Neurosci 30(49):16523–16535
Leite JP, Neder L, Arisi GM, Carlotti CG Jr, Assirati JA, Moreira JE (2005) Plasticity, synaptic strength, and epilepsy: what can we learn from ultrastructural data? Epilepsia 46(Suppl 5):134–141
Li HB, Mao RR, Zhang JC, Yang Y, Cao J, Xu L (2008) Antistress effect of TRPV1 channel on synaptic plasticity and spatial memory. Biol Psychiatry 64(4):286–292
Lizanecz E, Bagi Z, Pasztor ET et al (2006) Phosphorylation-dependent desensitization by anandamide of vanilloid receptor-1 (TRPV1) function in rat skeletal muscle arterioles and in Chinese hamster ovary cells expressing TRPV1. Mol Pharmacol 69(3):1015–1023
Meador KJ (2007) The basic science of memory as it applies to epilepsy. Epilepsia 48(Suppl 9):23–25
Mezey E, Toth ZE, Cortright DN et al (2000) Distribution of mRNA for vanilloid receptor subtype 1 (VR1), and VR1-like immunoreactivity, in the central nervous system of the rat and human. Proc Natl Acad Sci U S A 97(7):3655–3660
Montell C (2001) Physiology, phylogeny, and functions of the TRP superfamily of cation channels. Sci STKE 2001(90):re1
Mori F, Ribolsi M, Kusayanagi H et al (2012) TRPV1 channels regulate cortical excitability in humans. J Neurosci 32(3):873–879
Oliveira MS, Pacheco LF, Mello CF, Cavalheiro EA, Garrido-Sanabria ER (2011) Epileptiform activity in the limbic system. Front Biosci (Schol Ed) 3:565–593
Olney JW, Collins RC, Sloviter RS (1986) Excitotoxic mechanisms of epileptic brain damage. Adv Neurol 44:857–877
Palmini A, Najm I, Avanzini G et al (2004) Terminology and classification of the cortical dysplasias. Neurology 62(6 Suppl 3):S2–S8
Pedersen SF, Owsianik G, Nilius B (2005) TRP channels: an overview. Cell Calcium 38(3–4):233–252
Peters JH, McDougall SJ, Fawley JA, Smith SM, Andresen MC (2010) Primary afferent activation of thermosensitive TRPV1 triggers asynchronous glutamate release at central neurons. Neuron 65(5):657–669
Pingle SC, Matta JA, Ahern GP (2007) Capsaicin receptor: TRPV1 a promiscuous TRP channel. Handb Exp Pharmacol 179(2):155–171
Premkumar LS, Bishnoi M (2011) Disease-related changes in TRPV1 expression and its implications for drug development. Curr Top Med Chem 11(17):2192–2209
Shetty AK, Zaman V, Shetty GA (2003) Hippocampal neurotrophin levels in a kainate model of temporal lobe epilepsy: a lack of correlation between brain-derived neurotrophic factor content and progression of aberrant dentate mossy fiber sprouting. J Neurochem 87(1):147–159
Shirakawa H, Yamaoka T, Sanpei K et al (2008) TRPV1 stimulation triggers apoptotic cell death of rat cortical neurons. Biochem Biophys Res Commun 377(4):1211–1215
Shu HF, Yu SX, Zhang CQ et al (2012) Expression of TRPV1 in cortical lesions from patients with tuberous sclerosis complex and focal cortical dysplasia type IIb. Brain Dev. doi:10.1016/j.braindev.2012.04.007
Spencer DD, Spencer SS, Mattson RH, Williamson PD, Novelly RA (1984) Access to the posterior medial temporal lobe structures in the surgical treatment of temporal lobe epilepsy. Neurosurgery 15(5):667–671
Steffens M, Schulze-Bonhage A, Surges R, Feuerstein TJ (2005) Fatty acid amidohydrolase in human neocortex-activity in epileptic and non-epileptic brain tissue and inhibition by putative endocannabinoids. Neurosci Lett 385(1):13–17
Suleiman J, Brenner T, Gill D et al (2011) VGKC antibodies in pediatric encephalitis presenting with status epilepticus. Neurology 76(14):1252–1255
Szallasi A (2002) Vanilloid (capsaicin) receptors in health and disease. Am J Clin Pathol 118(1):110–121
Szallasi A, Blumberg PM (1999) Vanilloid (Capsaicin) receptors and mechanisms. Pharmacol Rev 51(2):159–212
Toth A, Boczan J, Kedei N et al (2005) Expression and distribution of vanilloid receptor 1 (TRPV1) in the adult rat brain. Brain Res Mol Brain Res 135(1–2):162–168
Van Der Stelt M, Di Marzo V (2004) Endovanilloids. Putative endogenous ligands of transient receptor potential vanilloid 1 channels. Eur J Biochem 271(10):1827–1834
van Spronsen M, Hoogenraad CC (2010) Synapse pathology in psychiatric and neurologic disease. Curr Neurol Neurosci Rep 10(3):207–214
Volterra A, Meldolesi J (2005) Astrocytes, from brain glue to communication elements: the revolution continues. Nat Rev Neurosci 6(8):626–640
Zhang X, Huang J, McNaughton PA (2005) NGF rapidly increases membrane expression of TRPV1 heat-gated ion channels. EMBO J 24(24):4211–4223
Acknowledgment
This work was supported by National Natural Science Foundation of China (No. 81071043, 81100975), Natural Science Foundation Project of CQ CSTC (No. 2011JJ0124) and China Postdoctoral Science Foundation (NO. 20110491854).
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Sun, FJ., Guo, W., Zheng, DH. et al. Increased Expression of TRPV1 in the Cortex and Hippocampus from Patients with Mesial Temporal Lobe Epilepsy. J Mol Neurosci 49, 182–193 (2013). https://doi.org/10.1007/s12031-012-9878-2
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DOI: https://doi.org/10.1007/s12031-012-9878-2