Skip to main content

Advertisement

SpringerLink
Log in

Effect of Hippocampal Overexpression of Dopamine Neurotrophic Factor (CDNF) on Behavior of Mice with Genetic Predisposition to Depressive-Like Behavior

  • Published:
Biochemistry (Moscow) Aims and scope Submit manuscript

Abstract

Cerebral dopamine neurotrophic factor (CDNF) is a promising agent for Parkinson’s disease treatment. However, its role in regulation of non-motor behavior including various psychopathologies remains unclear. In this regard, the aim of the present work was to study effect of CDNF overexpression in hippocampus on behavior of the ASC mice (Antidepressant Sensitive Cataleptics) with genetic predisposition to depressive-like behavior. CDNF overexpression in the mouse hippocampal neurons was induced using an adeno-associated viral vector. Four weeks after stereotaxic injection of the AAV-CDNF construct into the dorsal hippocampus home cage activity, exploratory, anxious and depressive-like types of behavior, as well as spatial and associative learning were assessed. We found significant improvements in the dynamics of spatial learning in the Morris water maze in the CDNF-overexpressing animals. At the same time, no effect of CDNF was found on other types of behavior under study. Behavior of the experimental animals under home cage conditions did not differ from that in the control group, except for the decrease in the total amount of food eaten and slight increase in the number of sleep episodes during the light phase of the day. In the present study we also attempted to determine molecular basis for the above-mentioned changes through assessment of the gene expression pattern. We did not find significant changes in the mRNA level of key kinases genes involved in neuroplasticity and neuronal survival, as well as genes encoding receptors for the main neurotransmitter systems. However, the CDNF-overexpressing animals showed increased level of the spliced Xbp indicating activation of the Ire1α/Xbp-1 pathway traditionally associated with ER stress. Immunohistochemical analysis showed that CDNF was co-localized with the ER marker calreticulin. Thus, the effects of endogenous CDNF on behavior that we have found could be mediated by a specific molecular cascade, which emphasizes its difference from the classical neurotrophic factors.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1.
Fig. 2.
Fig. 3.
Fig. 4.
Fig. 5.
Fig. 6.
Fig. 7.

Similar content being viewed by others

Abbreviations

AAV:

Adeno-associated virus vector

ASC:

Antidepressant Sensitive Catalepsy mice

CDNF:

cerebral dopamine neurotrophic factor

ER:

endoplasmic reticulum

Ire1 α:

endoribonuclease inositol-requiring enzyme 1 α

MANF:

mesencephalic astrocyte-derived neurotrophic factor

UPR:

unfolded protein response

XBP1:

X-box binding protein l

References

  1. Lindholm, P., Voutilainen, M. H., Laurén, J., Peränen, J., Leppänen, V.-M., Andressoo, J.-O., Lindahl, M., Janhunen, S., Kalkkinen, N., Timmusk, T., Tuominen, R. K., and Saarma, M. (2007) Novel neurotrophic factor CDNF protects and rescues midbrain dopamine neurons in vivo, Nature, 448, 73-77, https://doi.org/10.1038/nature05957.

    Article  CAS  PubMed  Google Scholar 

  2. Parkash, V., Lindholm, P., Peränen, J., Kalkkinen, N., Oksanen, E., Saarma, M., Leppänen, V.-M, and Goldman, A. (2009) The structure of the conserved neurotrophic factors MANF and CDNF explains why they are bifunctional, Protein Eng. Des. Sel., 22, 233-241, https://doi.org/10.1093/protein/gzn080.

    Article  CAS  PubMed  Google Scholar 

  3. Voutilainen, M. H., Bäck, S., Peränen, J., Lindholm, P., Raasmaja, A., Männistö, P. T., Saarma, M., and Tuominen, R. K. (2011) Chronic infusion of CDNF Prevents 6-OHDA-induced deficits in a rat model of Parkinson’s disease, Exp. Neurol., 228, 99-108, https://doi.org/10.1016/j.expneurol.2010.12.013.

    Article  CAS  PubMed  Google Scholar 

  4. Lindholm, D., Wootz, H., and Korhonen, L. (2006) ER stress and neurodegenerative diseases, Cell Death Differ., 13, 385-392, https://doi.org/10.1038/sj.cdd.4401778.

    Article  CAS  PubMed  Google Scholar 

  5. Garea-Rodríguez, E., Eesmaa, A., Lindholm, P., Schlumbohm, C., König, J., Meller, B., Krieglstein, K., Helms, G., Saarma, M., and Fuchs, E. (2016) Comparative analysis of the effects of neurotrophic factors CDNF and GDNF in a nonhuman primate model of Parkinson’s disease, PLoS One, 11, e0149776, https://doi.org/10.1371/journal.pone.0149776.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Raykhel, I., Alanen, H., Salo, K., Jurvansuu, J., Van, D. N., Latva-Ranta, M., and Ruddock, L. (2007) A molecular specificity code for the three mammalian KDEL receptors, J. Cell Biol., 179, 1193-1204, https://doi.org/10.1083/jcb.200705180.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Lindholm, P., and Saarma, M. (2010) Novel CDNF/MANF family of neurotrophic factors, Dev. Neurobiol., 70, 360-371, https://doi.org/10.1002/dneu.20760.

    Article  CAS  PubMed  Google Scholar 

  8. Apostolou, A., Shen, Y., Liang, Y., Luo, J., and Fang, S. (2008) Armet, a UPR-upregulated protein, inhibits cell proliferation and ER stress-induced cell death, Exp. Cell Res., 314, 2454-2467, https://doi.org/10.1016/j.yexcr.2008.05.001.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Bruhn, H. (2005) A short guided tour through functional and structural features of saposin-like proteins, Biochem. J., 389, 249-257, https://doi.org/10.1042/BJ20050051.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Mätlik, K., Yu, L., Eesmaa, A., Hellman, M., Lindholm, P., Peränen, J., Galli, E., Anttila, J., Saarma, M., Permi, P., Airavaara, M., and Arumäe, U. (2015) Role of two sequence motifs of mesencephalic astrocyte-derived neurotrophic factor in its survival-promoting activity, Cell Death Dis., 6, e2032, https://doi.org/10.1038/cddis.2015.371.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Božok, V., Yu, L., Palgi, J., and Arumäe, U. (2018) Antioxidative CXXC peptide motif from mesencephalic astrocyte-derived neurotrophic factor antagonizes programmed cell death, Front. Cell Dev. Biol., 6, 106, https://doi.org/10.3389/fcell.2018.00106.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Lindahl, M., Chalazonitis, A., Palm, E., Pakarinen, E., Danilova, T., Phamb, T. D., Setlikb, W., Rao, M., Võikar, V., Huotari, J., Kopra, J., Andressooa, J.-O., Piepponend, P. T., Airavaaraa, M., Panhelainen, A., Gershon, M. D., and Saarma, M. (2020) Cerebral dopamine neurotrophic factor-deficiency leads to degeneration of enteric neurons and altered brain dopamine neuronal function in mice, Neurobiol. Dis., 134, 104696, https://doi.org/10.1016/j.nbd.2019.104696.

    Article  CAS  PubMed  Google Scholar 

  13. Chen, Y.-C. C., Baronio, D., Semenova, S., Abdurakhmanova, S., and Panula, P. (2020) Cerebral dopamine neurotrophic factor regulates multiple neuronal subtypes and behavior, J. Neurosci., 40, 6146-6164, https://doi.org/10.1523/JNEUROSCI.2636-19.2020.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Kemppainen, S., Lindholm, P., Galli, E., Lahtinen, H.-M. M., Koivisto, H., Hämäläinena, E., Saarmab, M., and Tanila, H. (2015) Cerebral dopamine neurotrophic factor improves long-term memory in APP/PS1 transgenic mice modeling Alzheimer’s disease as well as in wild-type mice, Behav. Brain Res., 291, 1-11, https://doi.org/10.1016/j.bbr.2015.05.002.

    Article  CAS  PubMed  Google Scholar 

  15. Voutilainen, M. H., De Lorenzo, F., Stepanova, P., Bäck, S., Yu, L.-Y., Lindholm, P., Pörsti, E., Saarma, M., Männistö, P. T., and Tuominen, R. K. (2017) Evidence for an additive neurorestorative effect of simultaneously administered CDNF and GDNF in hemiparkinsonian rats: implications for different mechanism of action, eNeuro, 4, ENEURO.0117-16.2017, https://doi.org/10.1523/ENEURO.0117-16.2017.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Kesner, R. P. (2018) An analysis of dentate gyrus function (an update), Behav. Brain Res., 354, 84-91, https://doi.org/10.1016/J.BBR.2017.07.033.

    Article  PubMed  Google Scholar 

  17. Papp, G., Witter, M. P., and Treves, A. (2007) The CA3 network as a memory store for spatial representations, Learn. Mem., 14, 732-744, https://doi.org/10.1101/LM.687407.

    Article  PubMed  Google Scholar 

  18. Fredes, F., and Shigemoto, R. (2021) The role of hippocampal mossy cells in novelty detection, Neurobiol. Learn. Mem., 183, 107486, https://doi.org/10.1016/J.NLM.2021.107486.

    Article  PubMed  Google Scholar 

  19. Sun, D., Mei, L., and Xiong, W. C. (2023) Dorsal dentate gyrus, a key regulator for mood and psychiatric disorders, Biol. Psychiatry, 93, 1071-1080, https://doi.org/10.1016/J.BIOPSYCH.2023.01.005.

    Article  PubMed  Google Scholar 

  20. Kondaurova, E. M., Bazovkina, D. V., Kulikov, A. V., and Popova, N. K. (2006) Selective Breeding for catalepsy changes the distribution of microsatellite D13Mit76 alleles linked to the 5-HT1A serotonin receptor gene in mice, Genes, Brain Behav., 5, 596-601, https://doi.org/10.1111/j.1601-183X.2006.00212.x.

    Article  CAS  PubMed  Google Scholar 

  21. Kulikov, A. V., Bazovkina, D. V., Kondaurova, E. M., and Popova, N. K. (2008) Genetic structure of hereditary catalepsy in mice, Genes Brain Behav., 7, 506-512, https://doi.org/10.1111/j.1601-183X.2008.00387.x.

    Article  CAS  PubMed  Google Scholar 

  22. Kulikov, A. V., Kozlachkova, E. Y., Maslova, G. B., and Popova, N. K. (1993) Inheritance of predisposition to catalepsy in mice, Behav. Genet., 23, 379-384, https://doi.org/10.1007/BF01067439.

    Article  CAS  PubMed  Google Scholar 

  23. Tikhonova, M. A., Lebedeva, V. V., Kulikov, A. V., Bazovkina, D. V., and Popova, N. K. (2006) Effect of imipramine on the behavior and cerebral 5-HT1A serotonin receptors in mice genetically predisposed to catalepsy, Bull. Exp. Biol. Med., 141, 48-50, https://doi.org/10.1007/s10517-006-0090-7.

    Article  CAS  PubMed  Google Scholar 

  24. Tikhonova, M. A., Alperina, E. L., Tolstikova, T. G., Bazovkina, D. V., Di, V. Y., Idova, G. V., Kulikov, A. V., and Popova, N. K. (2010) Effects of chronic fluoxetine treatment on catalepsy and the immune response in mice with a genetic predisposition to freezing reactions: the roles of types 1A and 2A serotonin receptors and the Tph2 and SERT genes, Neurosci. Behav. Physiol., 40, 521-527, https://doi.org/10.1007/s11055-010-9291-7.

    Article  CAS  PubMed  Google Scholar 

  25. Bazovkina, D. V., Kulikov, A. V., Kondaurova, E. M., and Popova, N. K. (2005) Selection for the predisposition to catalepsy enhances depressive-like traits in mice, Russ. J. Genet., 41, 1002-1007, https://doi.org/10.1007/s11177-005-0191-9.

    Article  CAS  Google Scholar 

  26. Naumenko, V. S., Kondaurova, E. M., Bazovkina, D. V., Tsybko, A. S., Tikhonova, M. A., Kulikov, A. V., and Popova, N. K. (2012) Effect of brain-derived neurotrophic factor on behavior and key members of the brain serotonin system in genetically predisposed to behavioral disorders mouse strains, Neuroscience, 214, 59-67, https://doi.org/10.1016/j.neuroscience.2012.04.031.

    Article  CAS  PubMed  Google Scholar 

  27. Björkholm, C., and Monteggia, L. M. (2016) BDNF – a key transducer of antidepressant effects, Neuropharmacology, 102, 72-79, https://doi.org/10.1016/j.neuropharm.2015.10.034.

    Article  CAS  PubMed  Google Scholar 

  28. Caviedes, A., Lafourcade, C., Soto, C., and Wyneken, U. (2017) BDNF/NF-ΚB signaling in the neurobiology of depression, Curr. Pharm. Des., 23, 3154-3163, https://doi.org/10.2174/1381612823666170111141915.

    Article  CAS  PubMed  Google Scholar 

  29. Mondal, A. C., and Fatima, M. (2019) Direct and indirect evidences of BDNF and NGF as key modulators in depression: role of antidepressants treatment, Int. J. Neurosci., 129, 283-296, https://doi.org/10.1080/00207454.2018.1527328.

    Article  CAS  PubMed  Google Scholar 

  30. Naumenko, V. S., Bazovkina, D. V., Semenova, A. A., Tsybko, A. S., Il’chibaeva, T. V., Kondaurova, E. M., and Popova, N. K. (2013) Effect of glial cell line-derived neurotrophic factor on behavior and key members of the brain serotonin system in mouse strains genetically predisposed to behavioral disorders, J. Neurosci. Res., 91, 1628-1638, https://doi.org/10.1002/jnr.23286.

    Article  CAS  PubMed  Google Scholar 

  31. Chen, S.-H., Haam, J., Walker, M., Scappini, E., Naughton, J., and Martin, N. P. (2019) Recombinant viral vectors as neuroscience tools, Curr. Protoc. Neurosci., 87, e67, https://doi.org/10.1002/cpns.67.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Kondaurova, E. M., Plyusnina, A. V., Ilchibaeva, T. V., Eremin, D. V., Rodnyy, A. Y., Grygoreva, Y. D., and Naumenko, V. S. (2021) Effects of a Cc2d1a/Freud-1 knockdown in the hippocampus on behavior, the serotonin system, and BDNF, Int. J. Mol. Sci., 22, 13319, https://doi.org/10.3390/ijms222413319.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Kondaurova, E. M., Belokopytova, I. I., Kulikova, E. A., Khotskin, N. V., Ilchibaeva, T. V., Tsybko, A. S., Popova, N. K., and Naumenko, V. S. (2023) On the role of serotonin 5-HT(1A) receptor in autistic-like behavior: cross talk of 5-HT and BDNF systems, Behav. Brain Res., 438, 114168, https://doi.org/10.1016/j.bbr.2022.114168.

    Article  CAS  PubMed  Google Scholar 

  34. Kulikov, A. V., Naumenko, V. S., Voronova, I. P., Tikhonova, M. A., and Popova, N. K. (2005) Quantitative RT-PCR assay of 5-HT1A and 5-HT2A serotonin receptor MRNAs using genomic DNA as an external standard, J. Neurosci. Methods, 141, 97-101, https://doi.org/10.1016/J.JNEUMETH.2004.06.005.

    Article  CAS  PubMed  Google Scholar 

  35. Naumenko, V. S., and Kulikov, A. V. (2006) Quantitative assay of 5-HT1A receptor gene expression in the brain, Mol. Biol., 40, 30-36, https://doi.org/10.1134/S0026893306010067.

    Article  CAS  Google Scholar 

  36. Naumenko, V. S., Osipova, D. V., Kostina, E. V., and Kulikov, A. V. (2008) Utilization of a two-standard system in real-time PCR for quantification of gene expression in the brain, J. Neurosci. Methods, 170, 197-203, https://doi.org/10.1016/j.jneumeth.2008.01.008.

    Article  CAS  PubMed  Google Scholar 

  37. Kulikov, A. V., Tikhonova, M. A., and Kulikov, V. A. (2008) Automated measurement of spatial preference in the open field test with transmitted lighting, J. Neurosci. Methods, 170, 345-351, https://doi.org/10.1016/j.jneumeth.2008.01.024.

    Article  PubMed  Google Scholar 

  38. Khotskin, N. V., Plyusnina, A. V., Kulikova, E. A., Bazhenova, E. Y., Fursenko, D. V., Sorokin, I. E., Kolotygin, I., Mormedec, P., Tereninac, E. E., Sheveleva, O. B., and Kulikov, A. V. (2019) On association of the lethal yellow (AY) mutation in the agouti gene with the alterations in mouse brain and behavior, Behav. Brain Res., 359, 446-456, https://doi.org/10.1016/j.bbr.2018.11.013.

    Article  CAS  PubMed  Google Scholar 

  39. Kulikov, A. V., Morozova, M. V., Kulikov, V. A., Kirichuk, V. S., and Popova, N. K. (2010) Automated analysis of antidepressants’ effect in the forced swim test, J. Neurosci. Methods, 191, 26-31, https://doi.org/10.1016/j.jneumeth.2010.06.002.

    Article  CAS  PubMed  Google Scholar 

  40. Hetz, C., and Saxena, S. (2017) ER stress and the unfolded protein response in neurodegeneration, Nat. Rev. Neurol., 13, 477-491, https://doi.org/10.1038/nrneurol.2017.99.

    Article  CAS  PubMed  Google Scholar 

  41. Henderson, Y. O., Smith, G. P., and Parent, M. B. (2013) Hippocampal neurons inhibit meal onset, Hippocampus, 23, 100-107, https://doi.org/10.1002/hipo.22062.

    Article  CAS  PubMed  Google Scholar 

  42. Hannapel, R., Ramesh, J., Ross, A., Lalumiere, R. T., Roseberry, A. G., and Parent, M. B. (2019) Postmeal optogenetic inhibition of dorsal or ventral hippocampal pyramidal neurons increases future intake, eNeuro, 6, 457-475, https://doi.org/10.1523/ENEURO.0457-18.2018.

    Article  Google Scholar 

  43. Dubrovina, N. I., Zinov’ev, D. R., Zinov’eva, D. V., and Kulikov, A. V. (2009) Learning and extinction of a passive avoidance response in mice with high levels of predisposition to catalepsy, Neurosci. Behav. Physiol., 39, 475-480, https://doi.org/10.1007/s11055-009-9152-4.

    Article  CAS  PubMed  Google Scholar 

  44. Sinovyev, D. R., Dubrovina, N. I., and Kulikov, A. V. (2009) Development of amnesia in different mouse strains, Bull. Exp. Biol. Med., 147, 557-559, https://doi.org/10.1007/S10517-009-0583-2.

    Article  CAS  PubMed  Google Scholar 

  45. Lohoff, F. W., Bloch, P. J., Ferraro, T. N., Berrettini, W. H., Pettinati, H. M., Dackis, C. A., O’Brien, C. P., Kampman, K. M., and Oslin, D. W. (2009) Association analysis between polymorphisms in the conserved dopamine neurotrophic factor (CDNF) gene and cocaine dependence, Neurosci. Lett., 453, 199-203, https://doi.org/10.1016/j.neulet.2009.02.026.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Choi, J. M., Hong, J. H., Chae, M. J., Hung, N. P., Kang, H. S., Ma, H.-I., and Kim, Y. J. (2011) Analysis of mutations and the association between polymorphisms in the cerebral dopamine neurotrophic factor (CDNF) gene and Parkinson’s disease, Neurosci. Lett., 493, 97-101, https://doi.org/10.1016/j.neulet.2011.02.013.

    Article  CAS  PubMed  Google Scholar 

  47. Yang, Y., Yu, H., Li, W., Liu, B., Zhang, H., Ding, S., Lu, Y., Jiang, T., and Lv, L. (2018) Association between cerebral dopamine neurotrophic factor (CDNF) 2 polymorphisms and schizophrenia susceptibility and symptoms in the han chinese population, Behav. Brain Funct., 14, 1, https://doi.org/10.1186/s12993-017-0133-4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Arancibia, D., Zamorano, P., and Andrés, M. E. (2018) CDNF Induces the adaptive unfolded protein response and attenuates endoplasmic reticulum stress-induced cell death, Biochim. Biophys. Acta Mol. Cell Res., 1865, 1579-1589, https://doi.org/10.1016/j.bbamcr.2018.08.012.

    Article  CAS  PubMed  Google Scholar 

  49. Martínez, G., Vidal, R. L., Mardones, P., Serrano, F. G., Ardiles, A. O., Wirth, C., Valdés, P., Thielen, P., Schneider, B. L., Kerr, B., Valdés, J. L., Palacios, A. G., Inestrosa, N. C., Glimcher, L. H., and Hetz, C. (2016) Regulation of memory formation by the transcription factor XBP1, Cell Rep., 14, 1382-1394, https://doi.org/10.1016/j.celrep.2016.01.028.

    Article  CAS  PubMed  Google Scholar 

  50. Cissé, M., Duplan, E., Lorivel, T., Dunys, J., Bauer, C., Meckler, X., Gerakis, Y., Lauritzen, I., and Checler, F. (2017) The transcription factor XBP1s restores hippocampal synaptic plasticity and memory by control of the kalirin-7 pathway in Alzheimer model, Mol. Psychiatry, 22, 1562-1575, https://doi.org/10.1038/mp.2016.152.

    Article  CAS  PubMed  Google Scholar 

  51. Zhang, G., and Stackman, R. W. (2015) The role of serotonin 5-HT2A receptors in memory and cognition, Front. Pharmacol., 6, 225, https://doi.org/10.3389/fphar.2015.00225.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Rambousek, L., Palenicek, T., Vales, K., and Stuchlik, A. (2014) The effect of psilocin on memory acquisition, retrieval, and consolidation in the rat, Front. Behav. Neurosci., 8, 180, https://doi.org/10.3389/fnbeh.2014.00180.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Lindholm, P., and Saarma, M. (2022) Cerebral dopamine neurotrophic factor protects and repairs dopamine neurons by novel mechanism, Mol. Psychiatry, 27, 1310-1321, https://doi.org/10.1038/s41380-021-01394-6.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The study was carried out in the Center for Genetic Resources of Laboratory Animals of the Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences (ICG SB RAS), supported by the Ministry of Science and Higher Education of the Russian Federation (unique project identification no. RFMEFI62119X0023).

Funding

The study was financially supported by the Russian Science Foundation (grant no. 22-15-00011). Cost of animal maintenance was supported by the basic-research project no. FWNR-2022-0023.

Author information

Authors and Affiliations

  1. Federal Research Center Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, 630090, Novosibirsk, Russia

    Yana P. Kaminskaya, Tatiana V. Ilchibaeva, Nikita V. Khotskin, Vladimir S. Naumenko & Anton S. Tsybko

Authors
  1. Yana P. Kaminskaya
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tatiana V. Ilchibaeva
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nikita V. Khotskin
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Vladimir S. Naumenko
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Anton S. Tsybko
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Y.P.K. – experiments assessment, data analysis, writing the manuscript; T.V.I. – creation of viral constructs, visualization; N.V.Kh. – experiments assessment; A.S.T. – conceptualization, experiments assessment, manuscript revision; V.S.N. – manuscript revision, project supervision.

Corresponding author

Correspondence to Anton S. Tsybko.

Ethics declarations

The authors declare have no conflict of interest in financial or any other sphere declare. All experimental procedures were in compliance with the Guide for the Care and Use of Laboratory Animals, the Eighth Edition, Committee for the Update of the Guide for the Care and Use of Laboratory Animals; National Research Council © 2020 National Academy of Sciences (USA) for animal experiments, and the study protocol was approved by the ICG SB RAS ethics committee and registered at the ICG SB RAS (Protocol No. 34 of 15 June 2016).

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kaminskaya, Y.P., Ilchibaeva, T.V., Khotskin, N.V. et al. Effect of Hippocampal Overexpression of Dopamine Neurotrophic Factor (CDNF) on Behavior of Mice with Genetic Predisposition to Depressive-Like Behavior. Biochemistry Moscow 88, 1070–1091 (2023). https://doi.org/10.1134/S0006297923080035

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S0006297923080035

Keywords

Search

Navigation