Skip to main content
Top
Published in: Fluids and Barriers of the CNS 1/2009

Open Access 01-12-2009 | Research

Expression of TRPM8 in the distal cerebrospinal fluid-contacting neurons in the brain mesencephalon of rats

Authors: Jing Du, Xinwei Yang, Licai Zhang, Yin-ming Zeng

Published in: Fluids and Barriers of the CNS | Issue 1/2009

Login to get access

Abstract

Background

It has been shown that distal cerebrospinal fluid-contacting neurons (dCSF-CNs) exist near the ventral midline of the midbrain aqueduct and also in the grey matter of the inferior third ventricle and the fourth ventricle floor in the superior segment of the pons. The dCSF-CNs communicate between the cerebrospinal fluid (CSF) and the brain parenchyma and may participate in the transduction and regulation of pain signals. The cold sensation receptor channel, TRPM8 is involved in analgesia for neuropathic pain, but whether the TRPM8 receptor exists on dCSF-CNs remains unknown. However, there is preliminary evidence that TRPM8 is expressed in dCSF-CNs and may participate in the transmission and regulation of sensory information between brain parenchyma and cerebrospinal fluid (CSF) in rats.

Methods

Retrograde tracing of the cholera toxin subunit B labeled with horseradish peroxidase (CB-HRP) injected into the lateral ventricle was used to identify dCSF-CNs. A double-labeled immunofluorescent technique and laser scanning confocal microscopy were used to identify the expression of TRPM8 in dCSF-CNs. Software Image-Pro Plus was used to count the number of neurons in three sections where CB-HRP positive neurons were located in the mesencephalon of six rats.

Results

The cell bodies of CB-HRP-positive dCSF-CNs were found in the brain parenchyma near the midline of the ventral Aq, also in the grey of the 3V, and the 4V floor in the superior segment of the pons. In the mesencephalon their processes extended into the CSF. TRPM8 labeled neurons were also found in the same area as were CB-HRP/TRPM8 double-labeled neurons. CB-HRP/TRPM8 double-labeled neurons were found in 42.9 ± 2.3% of neurons labeled by TRPM8, and all CB-HRP-labeled neurons were also labeled with TPRM8.

Conclusion

This study has demonstrated that the cold sensation receptor channel, TRPM8, is localised within the dCSF-CNs of the mesencephalon. TRPM8 acts as receptor of dCSF-CNs for sensation transmission and pain regulation.
Appendix
Available only for authorised users
Literature
2.
go back to reference Frederick J, Buck ME, Matson DJ, Cortright DN: Increased TRPA1, TRPM8, and TRPV2 expression in dorsal root ganglia by nerve injury. Biochem Biophys Res Commun. 2007, 358: 1058-1064.CrossRefPubMed Frederick J, Buck ME, Matson DJ, Cortright DN: Increased TRPA1, TRPM8, and TRPV2 expression in dorsal root ganglia by nerve injury. Biochem Biophys Res Commun. 2007, 358: 1058-1064.CrossRefPubMed
3.
go back to reference Bautista DM, Siemens J, Glazer JM, Tsuruda PR, Basbaum AI, Stucky CL: The menthol receptor TRPM8 is the principal detector of environmental cold. Nature. 2007, 448: 204-208.CrossRefPubMed Bautista DM, Siemens J, Glazer JM, Tsuruda PR, Basbaum AI, Stucky CL: The menthol receptor TRPM8 is the principal detector of environmental cold. Nature. 2007, 448: 204-208.CrossRefPubMed
4.
go back to reference Dhaka A, Murray AN, Mathur J, Earley TJ, Petrus MJ, Patapoutian A: TRPM8 is required for cold sensation in mice. Neuron. 2007, 54: 371-378.CrossRefPubMed Dhaka A, Murray AN, Mathur J, Earley TJ, Petrus MJ, Patapoutian A: TRPM8 is required for cold sensation in mice. Neuron. 2007, 54: 371-378.CrossRefPubMed
5.
go back to reference Proudfoot CJ, Garry EM, Cottrell DF, Rosie R, Anderson H, Robertson DC: Analgesia mediated by the TRPM8 cold receptor in chronic neuropathic pain. Curr Biol. 2006, 16: 1591-1605.CrossRefPubMed Proudfoot CJ, Garry EM, Cottrell DF, Rosie R, Anderson H, Robertson DC: Analgesia mediated by the TRPM8 cold receptor in chronic neuropathic pain. Curr Biol. 2006, 16: 1591-1605.CrossRefPubMed
6.
go back to reference Vígh B, Silva MJM, Frank CL, Vincze C, Czirok SJ, Szabó A: The system of cerebrospinal fluid-contacting neurons. Its supposed role in the nonsynaptic signal transmission of the brain. Histol Histopathol. 2004, 19: 607-628.PubMed Vígh B, Silva MJM, Frank CL, Vincze C, Czirok SJ, Szabó A: The system of cerebrospinal fluid-contacting neurons. Its supposed role in the nonsynaptic signal transmission of the brain. Histol Histopathol. 2004, 19: 607-628.PubMed
7.
go back to reference Zhang LC, Zeng YM, Ting J, Cao JP, Wang MS: The distributions and signaling directions of the cerebrospinal fluid contacting neurons in the parenchyma of a rat brain. Brain Res. 2003, 989: 1-8.CrossRefPubMed Zhang LC, Zeng YM, Ting J, Cao JP, Wang MS: The distributions and signaling directions of the cerebrospinal fluid contacting neurons in the parenchyma of a rat brain. Brain Res. 2003, 989: 1-8.CrossRefPubMed
8.
go back to reference Lu X, Geng X, Zhang L, Zeng Y: The methodology for labeling the distal cerebrospinal fluid-contacting neurons in rats. J Neurosci Methods. 2008, 168: 98-103.CrossRefPubMed Lu X, Geng X, Zhang L, Zeng Y: The methodology for labeling the distal cerebrospinal fluid-contacting neurons in rats. J Neurosci Methods. 2008, 168: 98-103.CrossRefPubMed
10.
go back to reference Tsavaler L, Shapero MH, Morkowski S, Laus R: Trp-p8, a novel prostate-specific gene, is up-regulated in prostate cancer and other malignancies and shares high homology with transient receptor potential calcium channel proteins. Cancer Res. 2001, 61: 3760-3769.PubMed Tsavaler L, Shapero MH, Morkowski S, Laus R: Trp-p8, a novel prostate-specific gene, is up-regulated in prostate cancer and other malignancies and shares high homology with transient receptor potential calcium channel proteins. Cancer Res. 2001, 61: 3760-3769.PubMed
11.
go back to reference Peier AM, Moqrich A, Hergarden AC, Reeve AJ, Andersson DA, Story GM: A TRP channel that senses cold stimuli and menthol. Cell. 2002, 108: 705-715.CrossRefPubMed Peier AM, Moqrich A, Hergarden AC, Reeve AJ, Andersson DA, Story GM: A TRP channel that senses cold stimuli and menthol. Cell. 2002, 108: 705-715.CrossRefPubMed
12.
go back to reference McKemy DD, Neuhausser WM, Julius D: Identification of a cold receptor reveals a general role for TRP channels in thermosensation. Nature. 2002, 416: 52-58.CrossRefPubMed McKemy DD, Neuhausser WM, Julius D: Identification of a cold receptor reveals a general role for TRP channels in thermosensation. Nature. 2002, 416: 52-58.CrossRefPubMed
13.
go back to reference Nealen ML, Gold MS, Thut PD, Caterina MJ: TRPM8 mRNA is expressed in a subset of cold-responsive trigeminal neurons from rat. J Neurophysiol. 2003, 90: 515-520.CrossRefPubMed Nealen ML, Gold MS, Thut PD, Caterina MJ: TRPM8 mRNA is expressed in a subset of cold-responsive trigeminal neurons from rat. J Neurophysiol. 2003, 90: 515-520.CrossRefPubMed
14.
go back to reference Zhang L, Jones S, Brody K, Costa M, Brookes SJ: Thermosensitive transient receptor potential channels in vagal afferent neurons of the mouse. Am J Physiol Gastrointest Liver Physiol. 2004, 286 (6): G983-G991.CrossRefPubMed Zhang L, Jones S, Brody K, Costa M, Brookes SJ: Thermosensitive transient receptor potential channels in vagal afferent neurons of the mouse. Am J Physiol Gastrointest Liver Physiol. 2004, 286 (6): G983-G991.CrossRefPubMed
15.
go back to reference Mustafa S, Oriowo M: Cooling-induced contraction of the rat gastric fundus: mediation via transient receptor potential (TRP) cation channel TRPM8 receptor and Rho-kinase activation. Clin Exp Pharmacol Physiol. 2005, 32: 832-838.CrossRefPubMed Mustafa S, Oriowo M: Cooling-induced contraction of the rat gastric fundus: mediation via transient receptor potential (TRP) cation channel TRPM8 receptor and Rho-kinase activation. Clin Exp Pharmacol Physiol. 2005, 32: 832-838.CrossRefPubMed
16.
go back to reference Yang XR, Lin MJ, McIntosh LS, Sham JS: Functional expression of transient receptor potential melastatin-(TRPM) and vanilloid-related (TRPV) channels in pulmonary arterial and aortic smooth muscle. Am J Physiol Lung Cell Mol Physiol. 2006, 290: L1267-L1276.CrossRefPubMed Yang XR, Lin MJ, McIntosh LS, Sham JS: Functional expression of transient receptor potential melastatin-(TRPM) and vanilloid-related (TRPV) channels in pulmonary arterial and aortic smooth muscle. Am J Physiol Lung Cell Mol Physiol. 2006, 290: L1267-L1276.CrossRefPubMed
17.
go back to reference Henshall SM, Afar DE, Hiller J, Horvath LG, Quinn DI, Rasiah KK: Survival analysis of genome-wide gene expression profiles of prostate cancers identifies new prognostic targets of disease relapse. Cancer Res. 2003, 63: 4196-4203.PubMed Henshall SM, Afar DE, Hiller J, Horvath LG, Quinn DI, Rasiah KK: Survival analysis of genome-wide gene expression profiles of prostate cancers identifies new prognostic targets of disease relapse. Cancer Res. 2003, 63: 4196-4203.PubMed
18.
go back to reference Stein RJ, Santos S, Nagatomi J, Hayashi Y, Minnery BS, Xavier M: Cool (TRPM8) and hot (TRPV1) receptors in the bladder and male genital tract. J Urol. 2004, 172: 1175-1178.CrossRefPubMed Stein RJ, Santos S, Nagatomi J, Hayashi Y, Minnery BS, Xavier M: Cool (TRPM8) and hot (TRPV1) receptors in the bladder and male genital tract. J Urol. 2004, 172: 1175-1178.CrossRefPubMed
19.
go back to reference Segen J, Kemmler JE: Increased levels of Met-enkephalin-like immunoreactivity in the spinal cord CSF of rats with adrenal medullary transplants. Brain Res. 1989, 502: 1-10.CrossRef Segen J, Kemmler JE: Increased levels of Met-enkephalin-like immunoreactivity in the spinal cord CSF of rats with adrenal medullary transplants. Brain Res. 1989, 502: 1-10.CrossRef
20.
go back to reference Spaziante R, Merola B, Colao A: Beta-endorphin concentrations both in plasma and in cerebrospinal fluid in response to acute painful stimuli. J Neurosurg Sci. 1990, 34: 99-106.PubMed Spaziante R, Merola B, Colao A: Beta-endorphin concentrations both in plasma and in cerebrospinal fluid in response to acute painful stimuli. J Neurosurg Sci. 1990, 34: 99-106.PubMed
21.
go back to reference Strittmatter M, Grauer M, Isenberg E: Cerebrospinal fluid neuropeptides and monoaminergic transmitters in patients with trigeminal neuralgia. Headache. 1997, 37: 211-216.CrossRefPubMed Strittmatter M, Grauer M, Isenberg E: Cerebrospinal fluid neuropeptides and monoaminergic transmitters in patients with trigeminal neuralgia. Headache. 1997, 37: 211-216.CrossRefPubMed
22.
go back to reference Zubrzycka M, Janecka A: Substance P content in the cerebrospinal fluid and fluid perfusing cerebral ventricles during elicitation and inhibition of trigemino-hypoglossal reflex in rats. Brain Res. 2002, 941: 29-33.CrossRefPubMed Zubrzycka M, Janecka A: Substance P content in the cerebrospinal fluid and fluid perfusing cerebral ventricles during elicitation and inhibition of trigemino-hypoglossal reflex in rats. Brain Res. 2002, 941: 29-33.CrossRefPubMed
23.
go back to reference Marchand JE, Hagino N: Afferents to the periaqueductal gray in the rat. Neuroscience. 1983, 9: 95-106.CrossRefPubMed Marchand JE, Hagino N: Afferents to the periaqueductal gray in the rat. Neuroscience. 1983, 9: 95-106.CrossRefPubMed
24.
go back to reference Saka K, Salvert D, Touret M: Afferent connections of the nucleus raphe dorsalis in the cat as visualized by the horseradish peroxidase technique. Brain Res. 1977, 137: 11-35.CrossRef Saka K, Salvert D, Touret M: Afferent connections of the nucleus raphe dorsalis in the cat as visualized by the horseradish peroxidase technique. Brain Res. 1977, 137: 11-35.CrossRef
25.
go back to reference Gottschlich KW, Werner J: Effects of medial midbrain lesions on thermoresponsive neurons in the thalamus of the rat. Exp Brain Res. 1985, 57: 355-361.CrossRefPubMed Gottschlich KW, Werner J: Effects of medial midbrain lesions on thermoresponsive neurons in the thalamus of the rat. Exp Brain Res. 1985, 57: 355-361.CrossRefPubMed
26.
go back to reference Gao J, Zhang JX, Xu TL: Modulation of serotonergic projection from dorsal raphe nucleus to basolateral amygdala sleep-waking cycle of rats. Brain Res. 2002, 945: 60-70.CrossRefPubMed Gao J, Zhang JX, Xu TL: Modulation of serotonergic projection from dorsal raphe nucleus to basolateral amygdala sleep-waking cycle of rats. Brain Res. 2002, 945: 60-70.CrossRefPubMed
27.
go back to reference Monti JM, Jantos H, Monti D: Increased REM sleep after intra-dorsal raphe nucleus injection of foesinoxan or 8-OHDPAT: prevention with WAY 100635. Eur Neuropsychopharmacol. 2002, 12: 47-55.CrossRefPubMed Monti JM, Jantos H, Monti D: Increased REM sleep after intra-dorsal raphe nucleus injection of foesinoxan or 8-OHDPAT: prevention with WAY 100635. Eur Neuropsychopharmacol. 2002, 12: 47-55.CrossRefPubMed
28.
go back to reference Shima K, Nakahama H, Yamamoto M: Firing properties of two types of nucleus raphe dorsalis neurons during the sleep-waking cycle and their responses to sensory stimuli. Brain Res. 1986, 399: 317-326.CrossRefPubMed Shima K, Nakahama H, Yamamoto M: Firing properties of two types of nucleus raphe dorsalis neurons during the sleep-waking cycle and their responses to sensory stimuli. Brain Res. 1986, 399: 317-326.CrossRefPubMed
29.
go back to reference Morilak DA, Fornal C, Jacobs BL: Single unit activity of noradrenergic neurons in locus coerleus and serotonergic neurons in the nucleus raphe dorsalis of freely moving cats in relation to the cardiac cycle. Brain Res. 1986, 399: 262-270.CrossRefPubMed Morilak DA, Fornal C, Jacobs BL: Single unit activity of noradrenergic neurons in locus coerleus and serotonergic neurons in the nucleus raphe dorsalis of freely moving cats in relation to the cardiac cycle. Brain Res. 1986, 399: 262-270.CrossRefPubMed
30.
go back to reference Han FY, Xu YZ: Morphological observation in the median rapheal nuclei of the rabbit. Acta of 2nd Academiae medicine. Beijing. 1981, 4: 93-106. Han FY, Xu YZ: Morphological observation in the median rapheal nuclei of the rabbit. Acta of 2nd Academiae medicine. Beijing. 1981, 4: 93-106.
31.
go back to reference Koibuchi N, Kato M, Egawa TK: Suppression of human growth hormone (GH)-releasing hormone induced Gh secretion in pentobarbital-anesthetized tars after electrical stimulation of the midbrain central gray and several raphe nuclei. Endocrinology. 1988, 122: 659-664.CrossRefPubMed Koibuchi N, Kato M, Egawa TK: Suppression of human growth hormone (GH)-releasing hormone induced Gh secretion in pentobarbital-anesthetized tars after electrical stimulation of the midbrain central gray and several raphe nuclei. Endocrinology. 1988, 122: 659-664.CrossRefPubMed
32.
go back to reference Brown RE, Sergeeva OA, Eriksson KS, Haas HL: Convergent excitation of dorsal raphe serotonin neurons by multiple arousal systems. J Neurosci. 2002, 22: 8850-8859.PubMed Brown RE, Sergeeva OA, Eriksson KS, Haas HL: Convergent excitation of dorsal raphe serotonin neurons by multiple arousal systems. J Neurosci. 2002, 22: 8850-8859.PubMed
33.
go back to reference Ohliger FP, Horowitz J, Horwitz B: Enhanced adrenergic excitation of serotonergic dorsal raphe neurons in genetically obese rats. Neurosci Lett. 2002, 332: 107-CrossRef Ohliger FP, Horowitz J, Horwitz B: Enhanced adrenergic excitation of serotonergic dorsal raphe neurons in genetically obese rats. Neurosci Lett. 2002, 332: 107-CrossRef
34.
go back to reference Clark MS, Sexton TJ, Clain M: Overexpression of 5-HT1B receptor in dorsal raphe nucleus using Herpes Simplex Virus gene transfer increases anxiety behavior after inescapable stress. J Neurosci. 2002, 22: 4550-4562.PubMed Clark MS, Sexton TJ, Clain M: Overexpression of 5-HT1B receptor in dorsal raphe nucleus using Herpes Simplex Virus gene transfer increases anxiety behavior after inescapable stress. J Neurosci. 2002, 22: 4550-4562.PubMed
35.
go back to reference Picciotto MR, Picciotto MR, Brunzell DH, Caldarone BJ: Effect of nicotine and nicotinic receptors on anxiety and depression. Neuroreport. 2002, 13: 1097-1106.CrossRefPubMed Picciotto MR, Picciotto MR, Brunzell DH, Caldarone BJ: Effect of nicotine and nicotinic receptors on anxiety and depression. Neuroreport. 2002, 13: 1097-1106.CrossRefPubMed
36.
go back to reference Ishida Y, Hashiguchi H, Takeda R: Conditioned-fear stress in-creases Fos expression in monoaminergic and GABAergic neurons of the locus coeruleus and dorsal raphe nuclei. Synapse. 2002, 45: 46-51.CrossRefPubMed Ishida Y, Hashiguchi H, Takeda R: Conditioned-fear stress in-creases Fos expression in monoaminergic and GABAergic neurons of the locus coeruleus and dorsal raphe nuclei. Synapse. 2002, 45: 46-51.CrossRefPubMed
37.
go back to reference Keyama M, Yamanouchi K: Female sexual behaviors in male rats with dorsal raphe nucleus lesions. Brain Res Bull. 1993, 30: 705-709.CrossRef Keyama M, Yamanouchi K: Female sexual behaviors in male rats with dorsal raphe nucleus lesions. Brain Res Bull. 1993, 30: 705-709.CrossRef
38.
go back to reference Baumann B, Bielau H: Circumscribed numerical deficit of dorsal raphe neurons in mood disorders. Psychol Med. 2002, 32: 93-103.CrossRefPubMed Baumann B, Bielau H: Circumscribed numerical deficit of dorsal raphe neurons in mood disorders. Psychol Med. 2002, 32: 93-103.CrossRefPubMed
39.
go back to reference Chuma T, Taguchi K, Kato M: Modulation of noradrenergic and serotonergic transmission by noxious stimuli and intrathecal morphine differs in the dorsal raphe nucleus of anesthetized rat: in vivo voltammetric studies. Neurosci Res. 2002, 44: 37-44.CrossRefPubMed Chuma T, Taguchi K, Kato M: Modulation of noradrenergic and serotonergic transmission by noxious stimuli and intrathecal morphine differs in the dorsal raphe nucleus of anesthetized rat: in vivo voltammetric studies. Neurosci Res. 2002, 44: 37-44.CrossRefPubMed
40.
go back to reference Wang QP, Na K: The dorsal raphe: an important nucleus in pain modulation. Brain Res Bull. 1994, 34: 575-585.CrossRefPubMed Wang QP, Na K: The dorsal raphe: an important nucleus in pain modulation. Brain Res Bull. 1994, 34: 575-585.CrossRefPubMed
41.
go back to reference Wang MS, Zhang LC: Methodological comparison on the tracing CSF-CNs with HRP and CB-HRP. Acad Med. 1992, 12: 286-287. Wang MS, Zhang LC: Methodological comparison on the tracing CSF-CNs with HRP and CB-HRP. Acad Med. 1992, 12: 286-287.
Metadata
Title
Expression of TRPM8 in the distal cerebrospinal fluid-contacting neurons in the brain mesencephalon of rats
Authors
Jing Du
Xinwei Yang
Licai Zhang
Yin-ming Zeng
Publication date
01-12-2009
Publisher
BioMed Central
Published in
Fluids and Barriers of the CNS / Issue 1/2009
Electronic ISSN: 2045-8118
DOI
https://doi.org/10.1186/1743-8454-6-3

Other articles of this Issue 1/2009

Fluids and Barriers of the CNS 1/2009 Go to the issue