Stress-induced anhedonia is associated with an increase in Alzheimer’s disease-related markers
Open accessAbstract
BACKGROUND AND PURPOSE: Stress is believed to be associated with the development of neuropsychiatric disorders, including Alzheimer's disease (AD). We have studied mechanisms implicated in vulnerability to stress and the relationship with changes in AD-related markers. EXPERIMENTAL APPROACH: Anhedonia induced by a chronic mild stress (CMS) procedure, applied for 6 weeks, was used to select rats vulnerable or resistant to stress. Sucrose intake, the Porsolt forced swimming test and cognitive deficits in the novel object recognition test (NORT) were used to characterize vulnerable and resilient rats. The antidepressant venlafaxine (20 mg·kg(-1) p.o.) or saline was administered daily during the last 2 weeks of CMS. Biochemical markers affected by stress, PKB, ERK and synaptophysin, and those associated with AD, amyloid β-protein (Aβ), β-secretase (BACE1) and τ phosphorylation, were measured in the hippocampus. KEY RESULTS: After CMS, 40% of rats were resistant to the development of anhedonia (CMS-resistant to stress), whereas the remaining were responsive [CMS-anhedonic (CMSA)]. Only CMSA rats displayed significant increases in immobility time in the forced swimming test and cognitive deficits in the NORT, and significant decreases in synaptophysin, phosphorylated PKB and phosphorylated ERK1/2 expression in the hippocampus. Increased levels of Aβ40, BACE1 and τ phosphorylation were also found only in CMSA rats. All these effects in CMSA rats were reverted by treatment with venlafaxine. CONCLUSIONS AND IMPLICATIONS: Vulnerability to stress might constitute a risk factor for the development of AD, and pharmacological treatment with venlafaxine may represent a therapeutic strategy for the treatment of stress-related disorders, including AD.
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?
Anhedonia can be analyzed in mice using the sucrose preference test (SPT).
“which can be analyzed in mice using a sucrose preference test (SPT) (Briones et al., 2012; Liu et al., 2018).”
From LC3-Associated Endocytosis Facilitates β-Amyloid Clearance and Mitigates Neurodegeneration in Murine Alzheimer’s Disease (2019) · cites this paper as Briones et al., 2012
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
Depression: a new animal model sensitive to antidepressant treatments
PORSOLT, R. D., LE PICHON, M., & JALFRE, M. (1977) · Nature · doi:10.1038/266730a0 · Cited by 4,451 · see citing works
Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse
McGowan, P. O., Sasaki, A., D'Alessio, A. C., Dymov, S., Labonté, B., Szyf, M., Turecki, G., & Meaney, M. J. (2009) · Nature Neuroscience · doi:10.1038/nn.2270 · Cited by 3,531 · see citing works
A new one-trial test for neurobiological studies of memory in rats. 1: behavioral data
Ennaceur, A., & Delacour, J. (1988) · Behavioural Brain Research · doi:10.1016/0166-4328(88)90157-x · Cited by 3,223 · see citing works
Krishnan, V., Han, M.-H., Graham, D. L., Berton, O., Renthal, W., Russo, S. J., LaPlant, Q., Graham, A., Lutter, M., Lagace, D. C., et al. (2007) · Cell · doi:10.1016/j.cell.2007.09.018 · Cited by 2,307 · cited 5× · see citing works
“…to the development of stressinduced behavioural alterations could be associated with alterations in brain-derived neurotrophic factor (BDNF) (Krishnan et al., 2007; Taliaz et al., 2011), apoptotic pathways ( Bergström et al., 2008; Shishkina et al., 2010), AMPA receptors (Schmidt et al.,…”
BackgroundInfluentialSTRESS AND HIPPOCAMPAL PLASTICITY
McEwen, B. S. (1999) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.22.1.105 · Cited by 2,087 · see citing works
The HPA axis in major depression: classical theories and new developments
Pariante, C. M., & Lightman, S. L. (2008) · Trends in Neurosciences · doi:10.1016/j.tins.2008.06.006 · Cited by 2,009 · see citing works
Willner, P. (1997) · Psychopharmacology · doi:10.1007/s002130050456 · Cited by 1,832 · see citing works
Cipriani, A., Furukawa, T. A., Salanti, G., Geddes, J. R., Higgins, J. P., Churchill, R., Watanabe, N., Nakagawa, A., Omori, I. M., McGuire, H., et al. (2009) · The Lancet · doi:10.1016/s0140-6736(09)60046-5 · Cited by 1,654 · see citing works
Implications of resilience concepts for scientific understanding
RUTTER, M. (2006) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1376.002 · Cited by 1,648 · see citing works
Charney, D. S. (2004) · American Journal of Psychiatry · doi:10.1176/appi.ajp.161.2.195 · Cited by 1,605 · see citing works
Ownby, R. L., Crocco, E., Acevedo, A., John, V., & Loewenstein, D. (2006) · Archives of General Psychiatry · doi:10.1001/archpsyc.63.5.530 · Cited by 1,493 · see citing works
Neuronal loss correlates with but exceeds neurofibrillary tangles in Alzheimer's disease
Gómez‐Isla, T., Hollister, R., West, H., Mui, S., Growdon, J. H., Petersen, R. C., Parisi, J. E., & Hyman, B. T. (1997) · Annals of Neurology · doi:10.1002/ana.410410106 · Cited by 1,489 · see citing works
Psychobiology and molecular genetics of resilience
Feder, A., Nestler, E. J., & Charney, D. S. (2009) · Nature Reviews Neuroscience · doi:10.1038/nrn2649 · Cited by 1,272 · see citing works
Stress and cognition: are corticosteroids good or bad guys?
de Kloet, E. R., Oitzl, M. S., & Joëls, M. (1999) · Trends in Neurosciences · doi:10.1016/s0166-2236(99)01438-1 · Cited by 1,258 · see citing works
The Psychobiology of Depression and Resilience to Stress: Implications for Prevention and Treatment
Southwick, S. M., Vythilingam, M., & Charney, D. S. (2005) · Annual Review of Clinical Psychology · doi:10.1146/annurev.clinpsy.1.102803.143948 · Cited by 1,160 · see citing works
Competition among multiple memory systems: converging evidence from animal and human brain studies
Poldrack, R. A., & Packard, M. G. (2003) · Neuropsychologia · doi:10.1016/s0028-3932(02)00157-4 · Cited by 880 · see citing works
Sex, stress and the hippocampus: allostasis, allostatic load and the aging process
MCEWEN, B. (2002) · Neurobiology of Aging · doi:10.1016/s0197-4580(02)00027-1 · Cited by 753 · see citing works
Glucocorticoids increase amyloid-β and tau pathology in a mouse model of alzheimer’s disease
Green, K. N., Billings, L. M., Roozendaal, B., McGaugh, J. L., & LaFerla, F. M. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.2797-06.2006 · Cited by 623 · see citing works
Stress-Induced Anhedonia in Mice is Associated with Deficits in Forced Swimming and Exploration
Strekalova, T. V., Spanagel, R., Bartsch, D., Henn, F. A., & Gass, P. (2004) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300532 · Cited by 564 · see citing works
Preclinical models: status of basic research in depression
Nestler, E. J., Gould, E., & Manji, H. K. (2002) · Biological Psychiatry · doi:10.1016/s0006-3223(02)01405-1 · Cited by 559 · see citing works
Cognitive impairment associated to HPA axis hyperactivity after maternal separation in rats
Aisa, B., Tordera, R. M., Lasheras, B., Rı́o, J. D., & Ramírez, M. J. (2007) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2006.12.013 · Cited by 534 · see citing works
Self-citationGlycogen synthase kinase‐3 and the Alzheimer‐like state of microtubule‐associated protein tau
Mandelkow, E.-M., Drewes, G., Biernat, J., Gustke, N., Van Lint, J., Vandenheede, J. R., & Mandelkow, E. (1992) · FEBS Letters · doi:10.1016/0014-5793(92)81496-9 · Cited by 515 · see citing works
de Kloet, C. S., Vermetten, E., Geuze, E., Kavelaars, A., Heijnen, C. J., & Westenberg, H. G. M. (2006) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2005.08.002 · Cited by 503 · see citing works
Morris, R., Moser, E. I., Riedel, G., Martin, S. J., Sandin, J., Day, M., & O’Carroll, C. (2003) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2002.1264 · Cited by 480 · see citing works
Insulin signaling in the central nervous system: Learning to survive
van der Heide, L. P., Ramakers, G. M. J., & Smidt, M. P. (2006) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2006.06.003 · Cited by 444 · see citing works
Plasma Cortisol and Progression of Dementia in Subjects With Alzheimer-Type Dementia
Csernansky, J. G., Dong, H., Fagan, A. M., Wang, L., Xiong, C., Holtzman, D. M., & Morris, J. C. (2006) · American Journal of Psychiatry · doi:10.1176/appi.ajp.163.12.2164 · Cited by 426 · cited 1× · see citing works
“Csernansky et al. (2006) also showed that initial, higher serum glucocorticoids in the predementia clinical stage of AD predicts a more rapid cognitive decline.”
BackgroundPlasma Cortisol and Progression of Dementia in Subjects With Alzheimer-Type Dementia
Csernansky, J. G., Dong, H., Fagan, A. M., Wang, L., Xiong, C., Holtzman, D. M., & Morris, J. C. (2006) · American Journal of Psychiatry · doi:10.1176/ajp.2006.163.12.2164 · Cited by 421 · see citing works
Deletion of the background potassium channel TREK-1 results in a depression-resistant phenotype
Heurteaux, C., Lucas, G., Guy, N., Yacoubi, M. E., Thümmler, S., Peng, X.-D., Noble, F., Blondeau, N., Widmann, C., Borsotto, M., et al. (2006) · Nature Neuroscience · doi:10.1038/nn1749 · Cited by 375 · see citing works
Synaptophysin: leading actor or walk‐on role in synaptic vesicle exocytosis?
Valtorta, F., Pennuto, M., Bonanomi, D., & Benfenati, F. (2004) · BioEssays · doi:10.1002/bies.20012 · Cited by 346 · see citing works
Circadian oscillation of hippocampal MAPK activity and cAMP: implications for memory persistence
Eckel‐Mahan, K. L., Phan, T., Han, S., Wang, H., Chan, G. C. ‐., Scheiner, Z. S., & Storm, D. R. (2008) · Nature Neuroscience · doi:10.1038/nn.2174 · Cited by 344 · see citing works
Kumar‐Singh, S., Theuns, J., Broeck, B. V., Pirici, D. N., Vennekens, K., Corsmit, E., Cruts, M., Dermaut, B., Wang, R., & Broeckhoven, C. V. (2006) · Human Mutation · doi:10.1002/humu.20336 · Cited by 320 · see citing works
Soluble Aβ Inhibits Specific Signal Transduction Cascades Common to the Insulin Receptor Pathway
Townsend, M., Mehta, T., & Selkoe, D. J. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m610390200 · Cited by 318 · see citing works
Resilience to Chronic Stress Is Mediated by Hippocampal Brain-Derived Neurotrophic Factor
Taliaz, D., Loya, A., Gersner, R., Haramati, S., Chen, A., & Zangen, A. (2011) · The Journal of Neuroscience · doi:10.1523/jneurosci.5725-10.2011 · Cited by 311 · see citing works
Bremner, J. D., Vythilingam, M., Vermetten, E., Southwick, S. M., McGlashan, T., Staib, L. H., Soufer, R., & Charney, D. S. (2003) · Biological Psychiatry · doi:10.1016/s0006-3223(02)01891-7 · Cited by 299 · see citing works
Rénéric, J.-P., & Lucki, I. (1998) · Psychopharmacology · doi:10.1007/s002130050555 · Cited by 249 · see citing works
Jeong, Y. H., Park, C. H., Yoo, J., Shin, K. Y., Ahn, S., Kim, H., Lee, S. H., Emson, P. C., & Suh, Y. (2006) · The FASEB Journal · doi:10.1096/fj.05-4265fje · Cited by 241 · see citing works
Vulnerability to stress, anxiety, and development of dementia in old age
Wilson, R. S., Begeny, C. T., Boyle, P. A., Schneider, J. A., & Bennett, D. A. (2011) · The American Journal of Geriatric Psychiatry · doi:10.1097/jgp.0b013e31820119da · Cited by 208 · see citing works
Proneness to psychological distress and risk of Alzheimer disease in a biracial community
Wilson, R. S., Barnes, L. L., Bennett, D. A., Li, Y., Bienias, J. L., de Leon, C. F. M., & Evans, D. A. (2005) · Neurology · doi:10.1212/01.wnl.0000149525.53525.e7 · Cited by 201 · see citing works
BREMNER, J. D., & NARAYAN, M. (1998) · Development and Psychopathology · doi:10.1017/s0954579498001916 · Cited by 201 · see citing works
Numakawa, T., Kumamaru, E., Adachi, N., Yagasaki, Y., Izumi, A., & Kunugi, H. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0800888106 · Cited by 200 · see citing works
Elizalde, N., Gil-Bea, F. J., Ramírez, M. J., Aisa, B., Lasheras, B., del Rı́o, J. A., & Tordera, R. M. (2008) · Psychopharmacology · doi:10.1007/s00213-007-1035-1 · Cited by 195 · see citing works
Self-citationBergström, A., Jayatissa, M. N., Mørk, A., & Wiborg, O. (2007) · Brain Research · doi:10.1016/j.brainres.2007.12.025 · Cited by 195 · see citing works
Gene structure and organization of the human β‐secretase ( BACE ) promoter
Sambamurti, K., Kinsey, R., Maloney, B., Ge, Y., & Lahiri, D. K. (2004) · The FASEB Journal · doi:10.1096/fj.03-1378fje · Cited by 179 · see citing works
The amyloidogenic potential and behavioral correlates of stress
Catania, C., Sotiropoulos, I., Silva, R., Onofri, C., Breen, K. C., Sousa, N., & Almeida, O. F. X. (2007) · Molecular Psychiatry · doi:10.1038/sj.mp.4002101 · Cited by 175 · see citing works
Larsen, M. H., Mikkelsen, J. D., Hay-Schmidt, A., & Sandi, C. (2010) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2010.01.005 · Cited by 165 · see citing works
Cognitive Dysfunction, Hippocampal Atrophy and Glucocorticoid Feedback in Alzheimer’s Disease
Elgh, E., Åstot, A. L., Fagerlund, M., Eriksson, S., Olsson, T., & Näsman, B. (2005) · Biological Psychiatry · doi:10.1016/j.biopsych.2005.06.017 · Cited by 156 · see citing works
Corticotropin-Releasing Factor Receptors Differentially Regulate Stress-Induced Tau Phosphorylation
Rissman, R. A., Lee, K., Vale, W., & Sawchenko, P. E. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.5173-06.2007 · Cited by 150 · see citing works
Increased Vulnerability to Depressive-Like Behavior of Mice with Decreased Expression of VGLUT1
Garcia‐García, Á. L., Elizalde, N., Matrov, D., Harro, J., Wojcik, S. M., Venzala, E., Ramírez, M. J., Rı́o, J. D., & Tordera, R. M. (2009) · Biological Psychiatry · doi:10.1016/j.biopsych.2009.02.027 · Cited by 127 · see citing works
Self-citationInteractions Between Age, Stress and Insulin on Cognition: Implications for Alzheimer's Disease
Solas, M., Aisa, B., Mugueta, M. C., Del Río, J., Tordera, R. M., & Ramírez, M. J. (2010) · Neuropsychopharmacology · doi:10.1038/npp.2010.13 · Cited by 124 · see citing works
Self-citationHenningsen, K., Andreasen, J. T., Bouzinova, E. V., Jayatissa, M. N., Jensen, M. S., Redrobe, J. P., & Wiborg, O. (2008) · Behavioural Brain Research · doi:10.1016/j.bbr.2008.10.039 · Cited by 124 · see citing works
Bauer, M., Tharmanathan, P., Volz, H., Moeller, H., & Freemantle, N. (2009) · European Archives of Psychiatry and Clinical Neuroscience · doi:10.1007/s00406-008-0849-0 · Cited by 109 · see citing works
Schmidt, M. V., Trümbach, D., Weber, P., Wagner, K., Scharf, S. H., Liebl, C., Datson, N., Namendorf, C., Gerlach, T., Kühne, C., et al. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.4668-10.2010 · Cited by 91 · see citing works
CSF cortisol in Alzheimer's disease and mild cognitive impairment
Popp, J., Schaper, K., Kölsch, H., Cvetanovska, G., Rommel, F., Klingmüller, D., Dodel, R. C., Wüllner, U., & Jessen, F. (2007) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2007.07.007 · Cited by 83 · see citing works
HPA Axis Dysregulation Associated to Apolipoprotein E4 Genotype in Alzheimer's Disease
Gil-Bea, F. J., Aisa, B., Solomon, A., Solas, M., Mugueta, C., Winblad, B. G., Kivipelto, M., Cedazo-Mı́nguez, Á., & Ramírez, M. J. (2010) · Journal of Alzheimer s Disease · doi:10.3233/jad-2010-100663 · Cited by 80 · see citing works
Self-citationCzubak, A., Nowakowska, E., Kus, K., Burda, K., Metelska, J., Baer‐Dubowska, W., & Cichocki, M. (2009) · Pharmacological Reports · doi:10.1016/s1734-1140(09)70163-x · Cited by 71 · see citing works
Shishkina, G. T., Kalinina, T. S., Berezova, I. V., Bulygina, V. V., & Дыгало, Н. Н. (2010) · Behavioural Brain Research · doi:10.1016/j.bbr.2010.05.003 · Cited by 61 · see citing works
Dhikav, V., & Anand, K. S. (2007) · Medical Hypotheses · doi:10.1016/j.mehy.2006.09.038 · Cited by 50 · see citing works
Andreasen, J. T., Henningsen, K., Bate, S., Christiansen, S., & Wiborg, O. (2011) · Journal of Psychopharmacology · doi:10.1177/0269881110391831 · Cited by 46 · see citing works
Zhang, L., Shi, L., Liu, H., Meng, F., Liu, Y., Wu, H., Du, X., & Zhou, J. (2011) · The International Journal of Neuropsychopharmacology · doi:10.1017/s1461145711000411 · Cited by 45 · see citing works
Stress-Induced Tau Phosphorylation: Functional Neuroplasticity or Neuronal Vulnerability?
Rissman, R. A. (2009) · Journal of Alzheimer s Disease · doi:10.3233/jad-2009-1153 · Cited by 43 · see citing works
Cuadrado‐Tejedor, M., Ricobaraza, A., Río, J. D., Frechilla, D., Franco, R., Pérez‐Mediavilla, A., & García‐Osta, A. (2011) · Behavioural Brain Research · doi:10.1016/j.bbr.2011.01.005 · Cited by 42 · see citing works
Wang, Y., Xiao, Z., Liu, X., & Berk, M. (2011) · Human Psychopharmacology Clinical and Experimental · doi:10.1002/hup.1177 · Cited by 33 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Heckmann, B. L., Teubner, B. J. W., Tummers, B., Boada-Romero, E., Harris, L., Yang, M., Guy, C. S., Zakharenko, S. S., & Green, D. R. (2019) · Cell · doi:10.1016/j.cell.2019.05.056 · Cited by 503 · see citing works
“, 2015; Reichman and Coyne, 1995), which can be analyzed in mice using a sucrose preference test (SPT) (Briones et al., 2012; Liu et al., 2018).”
InfluentialMapping inflammation onto mood: inflammatory mediators of anhedonia
Swardfager, W., Rosenblat, J. D., Benlamri, M., & McIntyre, R. S. (2016) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2016.02.017 · Cited by 125 · see citing works
- Authors
- Briones, A., Gagno, S., Martisova, E., Dobarro, M., Aisa, B., Solas, M., Tordera, R., & Ramírez, M.
- Affiliations
- Universidad Autónoma de Chiapas (MX)
- Universidad de Navarra (ES)
- Venue
- British Journal of Pharmacology
- Publisher
- Wiley
- Published
- 2012-01-25
- Volume
- 165
- Issue
- 4
- Pages
- 897-907
- ISSN
- 0007-1188 (ISSN-L)
- 1476-5381
- PMC
- PMC3312487
- OpenAlex
- W1870249730
- Cited by
- 64
- References
- 62
- Citations by year
- 2026: 1 · 2025: 3 · 2023: 7 · 2022: 2 · 2021: 5 · 2020: 2 · 2019: 4 · 2018: 7 · 2017: 4 · 2016: 6 · 2015: 9 · 2014: 8 · 2013: 3 · 2012: 2
- FWCI
- 3.05
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- British Journal of Pharmacology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Consejo Nacional de Ciencia y Tecnología
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- chronic mild stress, Alzheimer's disease, stress vulnerability, venlafaxine, amyloid-beta, BACE1, tau phosphorylation, synaptophysin, Akt, ERK1/2, hippocampus, cognitive impairment, antidepressant treatment
- MeSH terms
- Venlafaxine Hydrochloride, Alzheimer Disease, Animals, Cognition, Corticosterone, Cyclohexanols, Hippocampus, Male, Self Administration, Stress, Psychological, Sucrose, Biomarkers, Amyloid beta-Peptides, Aspartic Acid Endopeptidases, Synaptophysin, tau Proteins, Rats, Wistar, Antidepressive Agents, Second-Generation, MAP Kinase Signaling System, Vesicular Transport Proteins, Proto-Oncogene Proteins c-akt, Rats, Amyloid Precursor Protein Secretases, Anhedonia
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
