Transcriptional expression of serotonergic regulators in laser‐captured microdissected dorsal raphe neurons of subjects with major depressive disorder: sex‐specific differences
Open accessAbstract
The relationship between serotonin (5‐HT) and major depressive disorder (MDD) has been extensively studied but certain aspects are still ambiguous. Given the evidence that 5‐HT neurotransmission is reduced in depressed subjects, it is possible that one or more of the 5‐HT regulators may be altered in the dorsal raphe nucleus (DR) of depressed subjects. Candidates that regulate 5‐HT synthesis and neuronal activity of 5‐HT neurons include intrinsic regulators such as tryptophan hydroxylase 2, 5‐HT autoreceptors, 5‐HT transporter and transcription factors, as well as afferent regulators such as estrogen and brain‐derived neurotrophic factor. The present study was designed to quantify mRNA concentrations of the above 5‐HT regulators in an isolated population of 5‐HT‐containing DR neurons of MDD subjects and gender‐matched psychiatrically normal control subjects. We found that mRNA concentrations of the 5‐HT1D receptor and the transcription factors, NUDR and REST, were significantly increased in DR‐captured neurons of female MDD subjects compared to female control subjects. No significant differences were found for the transcripts in male MDD subjects compared to male controls. This study reveals sex‐specific alterations in gene expression of the pre‐synaptic 5‐HT1D autoreceptors and 5‐HT‐related transcription factors, NUDR and REST, in DR neurons of women with MDD.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In postmortem brain specimens, there were no transcription differences between MDD men and controls, and levels of 5-HT1D receptors and transcription factors NUDR and REST in 5-HT-containing neurons in the ventral raphe nuclei were higher in MDD females.
“In postmortem brain specimens, there were no transcription differences between MDD men and controls, and the levels of 5-HT 1D receptors and the transcription factors NUDR and REST, which regulate 5-HT activity, in 5-HT-containing neurons in the ventral raphe nuclei were found to be higher in MDD females. 452”
From Major depressive disorder: hypothesis, mechanism, prevention and treatment (2024) · cites this paper as [452]
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT Method
Livak, K. J., & Schmittgen, T. D. (2001) · Methods · doi:10.1006/meth.2001.1262 · Cited by 180,860 · see citing works
Vandesompele, J., De Preter, K., Pattyn, F., Poppe, B., Van Roy, N., De Paepe, A., & Speleman, F. (2002) · Genome Biology · doi:10.1186/gb-2002-3-7-research0034 · Cited by 20,038 · see citing works
Diagnostic and Statistical Manual of Mental Disorders (DSM-IV)
Hu, R. J. (2003) · Elsevier eBooks · doi:10.1016/b0-12-226870-9/01070-4 · Cited by 9,167 · see citing works
Endicott, J. (1978) · Archives of General Psychiatry · doi:10.1001/archpsyc.1978.01770310043002 · Cited by 5,686 · see citing works
The RIN: an RNA integrity number for assigning integrity values to RNA measurements
Schroeder, A., Mueller, O., Stocker, S., Salowsky, R., Leiber, M., Gassmann, M., Lightfoot, S., Menzel, W., Granzow, M., & Ragg, T. (2006) · BMC Molecular Biology · doi:10.1186/1471-2199-7-3 · Cited by 2,623 · see citing works
Epidemiology of women and depression
Kessler, R. (2003) · Journal of Affective Disorders · doi:10.1016/s0165-0327(02)00426-3 · Cited by 2,006 · see citing works
Guideline to reference gene selection for quantitative real-time PCR
Radonić, A., Thulke, S., Mackay, I. M., Landt, O., Siegert, W., & Nitsche, A. (2003) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2003.11.177 · Cited by 1,645 · see citing works
RNA integrity and the effect on the real-time qRT-PCR performance
Fleige, S., & Pfaffl, M. W. (2006) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2005.12.003 · Cited by 1,488 · see citing works
Schoenherr, C. J., & Anderson, D. J. (1995) · Science · doi:10.1126/science.7871435 · Cited by 1,088 · see citing works
Validation of housekeeping genes for normalizing RNA expression in real-time PCR
Dheda, K. U. J., Huggett, J. F., Bustin, S. A., Johnson, M. A., Rook, G. A. W., & Zumla, A. I. (2004) · BioTechniques · doi:10.2144/04371rr03 · Cited by 1,025 · see citing works
BDNF and 5-HT: a dynamic duo in age-related neuronal plasticity and neurodegenerative disorders
Mattson, M. P., Maudsley, S., & Martin, B. (2004) · Trends in Neurosciences · doi:10.1016/j.tins.2004.08.001 · Cited by 942 · see citing works
Interaction between BDNF and Serotonin: Role in Mood Disorders
Martinowich, K., & Lu, B. (2008) · Neuropsychopharmacology · doi:10.1038/sj.npp.1301571 · Cited by 793 · see citing works
Lemonde, S., Turecki, G., Bakish, D., Du, L., Hrdina, P. D., Bown, C. D., Sequeira, A., Kushwaha, N., Morris, S. J., Basak, A., et al. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-25-08788.2003 · Cited by 733 · see citing works
Cellular changes in the postmortem hippocampus in major depression
Stockmeier, C. A., Mahajan, G. J., Konick, L. C., Overholser, J. C., Jurjus, G. J., Meltzer, H. Y., Uylings, H. B. M., Friedman, L., & Rajkowska, G. (2004) · Biological Psychiatry · doi:10.1016/j.biopsych.2004.08.022 · Cited by 732 · see citing works
Self-citationTricarico, C., Pinzani, P., Bianchi, S., Paglierani, M., Distante, V., Pazzagli, M., Bustin, S. A., & Orlando, C. (2002) · Analytical Biochemistry · doi:10.1016/s0003-2697(02)00311-1 · Cited by 581 · see citing works
Anatomy of the Serotonergic Systema
Törk, I. (1990) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1990.tb16870.x · Cited by 557 · see citing works
Stockmeier, C. A., Shapiro, L. A., Dilley, G. E., Kolli, T. N., Friedman, L., & Rajkowska, G. (1998) · Journal of Neuroscience · doi:10.1523/jneurosci.18-18-07394.1998 · Cited by 429 · see citing works
Self-citationThe influence of ovarian steroids on hypothalamic-pituitary-adrenal regulation in the female rat
Carey, M. P., Deterd, C. H., de Koning, J., Helmerhorst, F., & de Kloet, E. R. (1995) · Journal of Endocrinology · doi:10.1677/joe.0.1440311 · Cited by 385 · see citing works
Arango, V (2001) · Neuropsychopharmacology · doi:10.1016/s0893-133x(01)00310-4 · Cited by 368 · see citing works
Estrogen, serotonin, and mood disturbance: where is the therapeutic bridge?
Joffe, H., & Cohen, L. S. (1998) · Biological Psychiatry · doi:10.1016/s0006-3223(98)00169-3 · Cited by 284 · see citing works
Anatomic and functional topography of the dorsal raphe nucleus
ABRAMS, J. K., JOHNSON, P. L., HOLLIS, J. H., & LOWRY, C. A. (2004) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1296.005 · Cited by 284 · see citing works
Serotonergic Systems, Anxiety, and Affective Disorder
Lowry, C. A., Hale, M. W., Evans, A. K., Heerkens, J., Staub, D. R., Gasser, P. J., & Shekhar, A. (2008) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1410.004 · Cited by 265 · see citing works
Poul, E. L., Boni, C., Hanoun, N., Laporte, A., Laaris, N., Chauveau, J., Hamon, M., & Lanfumey, L. (2000) · Neuropharmacology · doi:10.1016/s0028-3908(99)00088-x · Cited by 238 · see citing works
Baker, K. G., Halliday, G. M., Hornung, J., Geffen, L. B., Cotton, R. G. H., & To¨rk, I. (1991) · Neuroscience · doi:10.1016/0306-4522(91)90043-n · Cited by 217 · see citing works
Serotonin-1A autoreceptor binding in the dorsal raphe nucleus of depressed suicides
Boldrini, M., Underwood, M. D., Mann, J. J., & Arango, V. (2008) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2007.05.004 · Cited by 190 · see citing works
Bach, H., Underwood, M. D., Kassir, S. A., Bakalian, M. J., Sibille, E. L., Tamir, H., Mann, J. J., & Arango, V. (2005) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300897 · Cited by 190 · see citing works
Serotonin 1A Receptor Binding and Treatment Response in Late-Life Depression
MELTZER, C. C., Price, J. C., Mathis, C. A., Butters, M. A., Ziolko, S. K., Moses‐Kolko, E. L., Mazumdar, S., Mulsant, B. H., Houck, P. R., Lopresti, B. J., et al. (2004) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300556 · Cited by 183 · see citing works
More tryptophan hydroxylase in the brainstem dorsal raphe nucleus in depressed suicides
Boldrini, M., Underwood, M. D., Mann, J. J., & Arango, V. (2005) · Brain Research · doi:10.1016/j.brainres.2005.01.083 · Cited by 174 · see citing works
Cytoarchitecture of the human dorsal raphe nucleus
Baker, K. G., Halliday, G. M., & Törk, I. (1990) · The Journal of Comparative Neurology · doi:10.1002/cne.903010202 · Cited by 174 · see citing works
Morphometry of the dorsal raphe nucleus serotonergic neurons in suicide victims
Underwood, M. D., Khaibulina, A. A., Ellis, S. P., Moran, A., Rice, P. M., Mann, J. J., & Arango, V. (1999) · Biological Psychiatry · doi:10.1016/s0006-3223(99)00043-8 · Cited by 165 · see citing works
Hiroi, R., McDevitt, R. A., & Neumaier, J. F. (2006) · Biological Psychiatry · doi:10.1016/j.biopsych.2005.10.019 · Cited by 161 · see citing works
Davidson, C., & Stamford, J. A. (1995) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.1995.tb13321.x · Cited by 157 · see citing works
Serotonin Receptors in Suicide Victims with Major Depression
Stockmeier, C. A. (1997) · Neuropsychopharmacology · doi:10.1016/s0893-133x(96)00170-4 · Cited by 153 · see citing works
Self-citationBach-Mizrachi, H., Underwood, M. D., Tin, A., Ellis, S. P., Mann, J. J., & Arango, V (2008) · Molecular Psychiatry · doi:10.1038/sj.mp.4002143 · Cited by 153 · see citing works
Anisman, H., Du, L., Palkovits, M., Faludi, G., Kovács, G. G., Szontagh-Kisházi, P., Merali, Z., & Poulter, M. O. (2008) · Journal of Psychiatry and Neuroscience · doi:10.1139/jpn.0815 · Cited by 143 · see citing works
Czesak, M., Lemonde, S., Peterson, E. A., Rogaeva, A., & Albert, P. R. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.2643-05.2006 · Cited by 138 · see citing works
Neumaier, J. (1996) · Neuropsychopharmacology · doi:10.1016/s0893-133x(96)00095-4 · Cited by 133 · see citing works
Xie, Z., Lee, S. P., O’Dowd, B. F., & George, S. R. (1999) · FEBS Letters · doi:10.1016/s0014-5793(99)00918-7 · Cited by 124 · see citing works
Bonaventure, P., Voorn, P., Luyten, W. H. M. L., Jurzak, M., Schotte, A., & Leysen, J. E. (1997) · Neuroscience · doi:10.1016/s0306-4522(97)00302-3 · Cited by 124 · see citing works
Brain 5-HT1A, 5-HT1D, and 5-HT2 Receptors in suicide victims
Arranz, B., Eriksson, A., Mellerup, E. T., Plenge, P., & Marcusson, J. O. (1994) · Biological Psychiatry · doi:10.1016/0006-3223(94)90044-2 · Cited by 120 · see citing works
Baca, E., García-García, M., & Porras-Chavarino, A. (2003) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/s0278-5846(03)00177-5 · Cited by 116 · see citing works
Jones, M. D., & Lucki, I. (2005) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300664 · Cited by 115 · see citing works
Hahm, K., Sum, E. Y. M., Fujiwara, Y., Lindeman, G. J., Visvader, J. E., & Orkin, S. H. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.5.2074-2082.2004 · Cited by 112 · see citing works
Moderate degradation does not preclude microarray analysis of small amounts of RNA
Schoor, O., Weinschenk, T., Hennenlotter, J., Corvin, S., Stenzl, A., Rammensee, H., & Stevanović, S. (2003) · BioTechniques · doi:10.2144/03356rr01 · Cited by 111 · see citing works
Trivedi, M. H., Lin, E. H. B., & Katon, W. J. (2007) · PubMed · Cited by 108 · see citing works
Circumscribed numerical deficit of dorsal raphe neurons in mood disorders
Baumann, B., Bielau, H., Krell, D., Agelink, M. W., Diekmann, S., Wurthmann, C., Trübner, K., Bernstein, H., Dános, P., & Bogerts, B. (2002) · Psychological Medicine · doi:10.1017/s0033291701004822 · Cited by 102 · see citing works
Wnt-1 dependent activation of the survival factor NF-?B in PC12 cells
Bournat, J. C., Brown, A. M. C., & Soler, A. P. (2000) · Journal of Neuroscience Research · doi:10.1002/1097-4547(20000701)61:1 · Cited by 100 · see citing works
Austin, M. C., Whitehead, R. E., Edgar, C. L., Janosky, J. E., & Lewis, D. A. (2002) · Neuroscience · doi:10.1016/s0306-4522(02)00289-0 · Cited by 99 · see citing works
Self-citationThe serotonin transporter in the midbrain of suicide victims with major depression
Bligh-Glover, W. Z., Kolli, T. N., Shapiro-Kulnane, L., Dilley, G. E., Friedman, L., Balraj, E. K., Rajkowska, G., & Stockmeier, C. A. (2000) · Biological Psychiatry · doi:10.1016/s0006-3223(99)00313-3 · Cited by 87 · see citing works
Self-citationSzewczyk, B., Albert, P. R., Burns, A. M., Czesak, M., Overholser, J. C., Jurjus, G. J., Meltzer, H. Y., Konick, L. C., Dieter, L., Herbst, N., et al. (2009) · The International Journal of Neuropsychopharmacology · doi:10.1017/s1461145708009012 · Cited by 87 · see citing works
Self-citationHaghighi, F., Bach, H., Huang, Y. Y., Arango, V., Shi, S., Dwork, A. J., Rosoklija, G. B., Sheng, H. T., Morozova, I., Ju, J., et al. (2008) · Molecular Psychiatry · doi:10.1038/sj.mp.4002127 · Cited by 81 · see citing works
Huggenvik, J. I., Michelson, R. J., Collard, M. W., Ziemba, A. J., Gurley, P., & Mowen, K. A. (1998) · Molecular Endocrinology · doi:10.1210/mend.12.10.0181 · Cited by 76 · see citing works
The Effects of Estradiol on Central Serotonergic Systems and Its Relationship to Mood in Women
Lasiuk, G. C., & Hegadoren, K. (2007) · Biological Research For Nursing · doi:10.1177/1099800407305600 · Cited by 68 · see citing works
Cognition, Mood Disorders, and Sex Hormone
Shively, C. A., & Bethea, C. L. (2004) · ILAR Journal · doi:10.1093/ilar.45.2.189 · Cited by 65 · see citing works
Serotonin transporter binding sites and mRNA levels in depressed persons committing suicide
Little, K. Y., McLauglin, D. P., Ranc, J., Gilmore, J. H., López, J. F., Watson, S. J., Carroll, F. I., & Butts, J. D. (1997) · Biological Psychiatry · doi:10.1016/s0006-3223(96)00301-0 · Cited by 64 · see citing works
Neumaier, J. F., Petty, F., Kramer, G. L., Szot, P., & Hamblin, M. W. (1997) · Biological Psychiatry · doi:10.1016/s0006-3223(96)00114-x · Cited by 51 · see citing works
Hiroi, R., & Neumaier, J. (2008) · Neuroscience · doi:10.1016/j.neuroscience.2008.10.016 · Cited by 50 · see citing works
Bonkale, W. L., Murdock, S., Janosky, J. E., & Austin, M. C. (2004) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2003.02225.x · Cited by 48 · see citing works
Self-citationPatel, P. D., Bochar, D. A., Turner, D. L., Meng, F., Mueller, H., & Pontrello, C. G. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m705120200 · Cited by 48 · see citing works
Lemonde, S., Rogaeva, A., & Albert, P. R. (2004) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2003.02223.x · Cited by 47 · see citing works
Stockmeier, C. A., Howley, E., Shi, X., Sobańska, A., Clarke, G. A., Friedman, L., & Rajkowska, G. (2009) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2009.01.001 · Cited by 40 · see citing works
Self-citationДыгало, Н. Н., Shishkina, G. T., Kalinina, T. S., Yudina, A., & Ovchinnikova, E. S. (2006) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2006.08.004 · Cited by 40 · see citing works
Klimek, V., Roberson, G., Stockmeier, C. A., & Ordway, G. A. (2003) · Journal of Psychiatric Research · doi:10.1016/s0022-3956(03)00045-1 · Cited by 33 · see citing works
Self-citationLowther, S., Katona, C., Crompton, M. R., & Horton, R. W. (1997) · Molecular Psychiatry · doi:10.1038/sj.mp.4000259 · Cited by 30 · see citing works
Localisation of mRNA for h5-HT 1B and h5-HT 1D receptors in human dorsal raphe
Bidmon, H. J., Schleicher, A., Wicke, K. M., et al. (2001) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/s002100000357 · Cited by 17 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- First MBSR Gibbon M Williams JBW 1996 Structured clinical interview for DSM-IV axis I disorders-patient edition Biometrics Research Department New York State Psychiatric Institute
Cited by
Sorted by citations
Major depressive disorder: hypothesis, mechanism, prevention and treatment
Cui, L., Li, S., Wang, S., Wu, X., Liu, Y., Yu, W., Wang, Y., Tang, Y., Xia, M., & Li, B. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01738-y · Cited by 1,061 · see citing works
Sex-specific transcriptional signatures in human depression
Labonté, B., Engmann, O., Purushothaman, I., Menard, C., Wang, J., Tan, C., Scarpa, J. R., Moy, G., Loh, Y.-H. E., Cahill, M., et al. (2017) · Nature Medicine · doi:10.1038/nm.4386 · Cited by 748 · see citing works
Sex differences: Transcriptional signatures of stress exposure in male and female brains
Brivio, E., Lopez, J. P., & Chen, A. (2020) · Genes, Brain and Behavior · doi:10.1111/gbb.12643 · Cited by 95 · see citing works
Kerman, I. A., Bernard, R., Bunney, W. E., Jones, E. G., Schatzberg, A. F., Myers, R. M., Barchas, J. D., Akil, H., Watson, S. J., & Thompson, R. C. (2012) · Frontiers in Neuroscience · doi:10.3389/fnins.2012.00135 · Cited by 59 · see citing works
Mingardi, J., La Via, L., Tornese, P., Carini, G., Trontti, K., Seguini, M., Tardito, D., Bono, F., Fiorentini, C., Elia, L., et al. (2021) · Neurobiology of Stress · doi:10.1016/j.ynstr.2021.100381 · Cited by 36 · see citing works
- Authors
- Goswami, D. B., May, W. L., Stockmeier, C. A., & Austin, M. C.
- Affiliations
- University of Mississippi Medical Center (US)
- Corresponding author
- Austin, Mark C.
- ORCID
- Stockmeier, Craig A.
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 2009-12-21
- Volume
- 112
- Issue
- 2
- Pages
- 397-409
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- PMC
- PMC3757563
- OpenAlex
- W1997782319
- Cited by
- 61
- References
- 65
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 3 · 2023: 4 · 2022: 8 · 2021: 4 · 2020: 3 · 2019: 4 · 2018: 1 · 2017: 5 · 2016: 3 · 2015: 4 · 2014: 2 · 2013: 4 · 2012: 7
- FWCI
- 3.13
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Neurochemistry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (5p20rr017701-10)
- National Center for Research Resources (P20-RR-017701, RR017701)
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- major depressive disorder, serotonin, dorsal raphe nucleus, 5-HT1D receptor, rest, sex differences, gene expression, tryptophan hydroxylase 2, 5-HT transporter, estrogen, brain-derived neurotrophic factor, laser capture microdissection
- MeSH terms
- RE1-Silencing Transcription Factor, Adult, Aged, Aged, 80 and over, Depressive Disorder, Major, Major Depressive Disorder, DNA-Binding Proteins, Female, Gene Expression Regulation, Humans, Lasers, Male, Middle Aged, Neurons, Nuclear Proteins, Raphe Nuclei, Receptors, Estrogen, Repressor Proteins, RNA, Messenger, Serotonin, Sex Factors, Transcription Factors, Tryptophan Hydroxylase, Protein Isoforms, Receptor, trkB, Microdissection, Receptor, Serotonin, 5-HT1D
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
