Sandra Ceccatelli

Sandra Ceccatelli

Professor
Telephone: +46852487586
Visiting address: Solnavägen 9 - kvarter D7, 17165 Solna
Postal address: C4 Neurovetenskap, C4 Forskning Ceccatelli, 171 77 Stockholm
Part of:

About me

  • Personal statement


    I am Professor of Neurotoxicology at the Department of Neuroscience, Karolinska Institutet (KI), Stockholm, Sweden, and Director of the KI Ming Wai Lau Centre for Reparative Medicine. My clinical experience as an MD specialized in Child neuropsychiatry reinforced my belief in basic research as essential to move forward our understanding of neurodevelopmental disorders. My research has been developing through the last 30 years starting with a Dr Med Sci thesis on neuroendocrine mechanisms of stress hormone secretion at the Karolinska Institutet and a post-doctoral period at the Laboratory of Neurobiology and Behaviour at the Rockefeller University; New York. Upon my return to Sweden, I established my own research group at the Department of Toxicology of Karolinska Institutet and acquired a solid expertise in cellular mechanisms of neurotoxicity.  

    My group studies the impact of adverse conditions linked to environmental and/or genetic factors on neurodevelopment with special reference to molecular mechanisms and functional outcome relevant to neurodevelopmental disorders. Since the very beginning my ambition was to address the complex issue of neurodevelopmental damage by using a comprehensive strategy stretching from behavioral to cellular and molecular analyses. To identify the intracellular mechanisms leading to neuronal damage, we have implemented many in vitro cell models including cell lines and primary cultures of different cell types related to the nervous system, such as neuronal and glial cells. Being interested in developmental neurotoxicity, we put a special effort in establishing relevant models based on neural stem cells. Using these models, we have made original contributions to characterize relevant pathways activated in programmed cell death/apoptosis induced by neurotoxic stimuli. A consistent part of my research has been devoted to the investigation of the neurodevelopmental effects of relevant environmental contaminants including MeHg, PFOS/PFOA, PCBs, Dioxins.  A special focus has been on the effectes of high levels of the main stress hormones glucocorticoids (GC) on neurodevelopment.

Research

  • Research progression

    The studies I made in the frame of my Dr. Med Sci. studies provided an important basis for understanding the neurochemistry and function of specific brain regions in the regulation of the response to stress. One of my major findings was achieved by using the novel marker for neuronal activity c-Fos which allowed the visualization of specific hypothalamic neuropeptidergic neurons activated by stress.

    -Ceccatelli S, Eriksson M, Hökfelt T. Distribution and coexistence of corticotropin-releasing factor-, neurotensin-, enkephalin-, cholecystokinin-, galanin- and vasoactive intestinal polypeptide/peptide histidine isoleucine-like peptides in the parvocellular part of the paraventricular nucleus. Neuroendocrinology. 1989 Mar;49(3):309-23. doi: 10.1159/000125133. PMID: 2469987.

    -Ceccatelli S, Villar MJ, Goldstein M, Hökfelt T. Expression of c-Fos immunoreactivity in transmitter-characterized neurons after stress. Proc Natl Acad Sci U S A. 1989 Dec;86(23):9569-73. doi: 10.1073/pnas.86.23.9569. PMID: 2512584; PMCID: PMC298539.

    -Ceccatelli S, Ernfors P, Villar MJ, Persson H, Hökfelt T. Expanded distribution of mRNA for nerve growth factor, brain-derived neurotrophic factor, and neurotrophin 3 in the rat brain after colchicine treatment. Proc Natl Acad Sci U S A. 1991 Nov 15;88(22):10352-6. doi: 10.1073/pnas.

    -Ceccatelli S, Hulting AL, Zhang X, Gustafsson L, Villar M, Hökfelt T. Nitric oxide synthase in the rat anterior pituitary gland and the role of nitric oxide in regulation of luteinizing hormone secretion. Proc Natl Acad Sci U S A. 1993 Dec 1;90(23):11292-6. doi: 10.1073/pnas.90.23.11292. PMID: 7504302; PMCID: PMC47968.

    We have been the first group at Karolinska Institutet Solna that established a behavioral unit for the computerized analysis of rodent home-cage behavior, where animals are tested in their social environment with minimal stress. Our studies have clearly shown that the analysis of behavior is a first-choice approach to detect subtle modifications induced by neurodevelopmental insults induced by stress or exposure to environmental contaminants.

    -Conti M, Spulber S, Raciti M, Ceccatelli S. Depressive-like phenotype induced by prenatal dexamethasone in mice is reversed by desipramine. Neuropharmacology, 2017 Nov;126:242-249. doi: 10.1016/j.neuropharm.2017.09.015.

    -Onishchenko N, Fischer C, Wan Ibrahim WN, Negri S, Spulber S, Cottica D, Ceccatelli S. Prenatal exposure to PFOS or PFOA alters motor function in mice in a sex-related manner. Neurotox Res. 2011 Apr;19(3):452-61. doi: 10.1007/s12640-010-9200-4.

    -Onishchenko N, Karpova N, Sabri F, Castrén E, Ceccatelli S. Long-lasting depression-like behavior and epigenetic changes of BDNF gene expression induced by perinatal exposure to methylmercury. J Neurochem. 2008 Aug;106(3):1378-87. doi: 10.1111/j.14159.2008.05484.

    -Onishchenko N, Tamm C, Vahter M, Hökfelt T, Johnson JA, Johnson DA, Ceccatelli S. Developmental exposure to methylmercury alters  learning and induces depression-like behavior in male mice. Toxicol Sci. 2007, Jun;97(2):428-37. doi: 10.1093/toxsci/kfl199.

    Almost all in vivo and in vitro experimental research used to be performed in males. Our group has been among the firsts that highlighted the relevance of sex-related differences in physiological and pathological responses. 

    -Edoff K, Raciti M, Moors M, Sundström E, Ceccatelli S. Gestational Age and Sex Influence the Susceptibility of Human Neural Progenitor Cells to Low Levels of MeHg. Neurotox Res. 2017 Nov;32(4):683-693.

    -Onishchenko N, Fischer C, W an Ibrahim W N, Negri S, Spulber S, Cottica D, Ceccatelli S. Prenatal exposure to PFOS or PFOA alters motor function in mice in a sex-related manner. Neurotox Res. 2011 Apr;19(3):452-61.

    -Spulber S, Rantamäki T, Nikkilä O, Castrén E, Weihe P, Grandjean P, Ceccatelli S. Effects of maternal smoking and exposure to methylmercury on brain-derived neurotrophic factor concentrations in umbilical cord serum. Toxicol Sci. 2010 Oct;117(2):263-9.

    -Vahter M, Akesson A, Lidén C, Ceccatelli S, Berglund M. Gender differences in the disposition and toxicity of metals. Environ Res. 2007 6/39 May;104(1):85-95. doi: 10.1016/j.envres.2006.08.003. Epub 2006 Sep 22.

    -Johansson C, Castoldi AF, Onishchenko N, Manzo L, Vahter M, Ceccatelli S. Neurobehavioural and molecular changes induced by methylmercury exposure during development. Neurotox Res. 2007 Apr;11(3-4):241-60.

    -Jurewicz J, Hanke W , Johansson C, Lundqvist C, Ceccatelli S, van den Hazel P, Saunders M, Zetterström R. Adverse health effects of children's exposure to pesticides: what do we really know and what can be done about it. Acta Paediatr Suppl. 2006 Oct;95(453):71-80.

    -Lundqvist C, Zuurbier M, Leijs M, Johansson C, Ceccatelli S, Saunders M, Schoeters G, ten Tusscher G, Koppe JG. The effects of PCBs and dioxins on child health. Acta Paediatr Suppl. 2006 Oct;95(453):55-64.

    -Giménez-Llort L, Ahlbom E, Daré E, Vahter M, Ögren S, Ceccatelli S. Prenatal exposure to methylmercury changes dopamine-modulated motor activity during early ontogeny: age and gender-dependent effects. Environ Toxicol Pharmacol. 2001 Jan 1;9(3):61-70.

    -Rossi AD, Ahlbom E, Ogren SO, Nicotera P, Ceccatelli S. Prenatal exposure to methylmercury alters locomotor activity of male but not female rats. Exp Brain Res. 1997 Dec;117(3):428-36. doi: 10.1007/s002210050237.

    The identification of mechanisms of neurotoxicity has been a major objective of our research.

    -Tamm C, Ceccatelli S. Mechanistic insight into neurotoxicity induced by developmental insults. Review, Biochem Biophys Res Commun. 2017 Jan 15;482(3):408-418. doi: 10.1016/j.bbrc.2016.10.087. Epub 2017 Feb 3.

    -Ceccatelli S, Daré E, Moors M. Methylmercury-induced neurotoxicity and apoptosis. Review, Chem Biol Interact. 2010 Nov 5;188(2):301-8. 

    -Tamm C, Sabri F, Ceccatelli S. Mitochondrial-mediated apoptosis in neural stem cells exposed to manganese. Review, Toxicol Sci. 2008 Feb;101(2):310-20. doi: 10.1093/toxsci/kfm267. Epub 2007 Oct 31. PMID: 17977900

    -Ceccatelli S, Tamm C, Sleeper E, Orrenius S. Neural stem cells and cell death. Review, Toxicol Lett. 2004 Apr 1;149(1-3):59-66. 

    We have been pioneering the use of neural stem cells to study the mechanisms behind neurodevelopmental insults induced by low levels of environmental contaminants and to implement neurodevelopmental toxicity testing.

    -Bose R, Spulber S, Ceccatelli S. The Threat Posed by Environmental Contaminants on Neurodevelopment: What Can We Learn from Neural Stem Cells? Int J Mol Sci. 2023 Feb 22;24(5):4338. doi: 10.3390/ijms24054338. PMID: 36901772; PMCID: PMC10002364.

    -Reis L, Raciti M, Rodriguez PG, Joseph B, Al Rayyes I, Uhlén P, Falk A, da Cunha Lima ST, Ceccatelli S. Glyphosate-based herbicide induces long-lasting impairment in neuronal and glial differentiation. Environ Toxicol. 2022 Aug;37(8):2044-2057. doi: 10.1002/tox.23549.

    -Gliga AR, Edoff K, Caputo F, Källman T, Blom H, Karlsson HL, Ghibelli L, Traversa E, Ceccatelli S, Fadeel B. Cerium oxide nanoparticles inhibit differentiation of neural stem cells. Sci Rep. 2017 Aug 24;7(1):9284.

    -Wan Ibrahim WN, Tofighi R, Onishchenko N, Rebellato P, Bose R, Uhlén P, Ceccatelli S. Perfluorooctane sulfonate induces neuronal and oligodendrocytic differentiation in neural stem cells and alters the expression of PPARγ in vitro and in vivo. Toxicol Appl Pharmacol. 2013 May 15;269(1):51-60. doi: 10.1016/j.taap.2013.03.003. Epub 2013 Mar 14. PMID: 23500012.

    -Ceccatelli S, Bose R, Edoff K, Onishchenko N, Spulber S. Long-lasting neurotoxic effects of exposure to methylmercury during development. J Intern Med. 2013 May;273(5):490-7. doi: 10.1111/joim.12045. PMID: 23600401.

    -Bose R, Onishchenko N, Edoff K, Janson Lang AM, Ceccatelli S. Inherited effects of low-dose exposure to methylmercury in neural stem cells. Toxicol Sci. 2012 Dec;130(2):383-90. doi: 10.1093/toxsci/kfs257. Epub 2012 Aug 23. PMID: 22918959.

    -Moors M, Bose R, Johansson-Haque K, Edoff K, Okret S, Ceccatelli S. Dickkopf 1 mediates glucocorticoid-induced changes in human neural progenitor cell proliferation and differentiation. Toxicol Sci. 2012 Feb;125(2):488-95. doi:10.1093/toxsci/kfr304. Epub 2011 Nov 1.

    -Tofighi R, Wan Ibrahim WN, Rebellato P, Andersson PL, Uhlén P, Ceccatelli S. Non-dioxin-like polychlorinated biphenyls interfere with neuronal differentiation of embryonic neural stem cells. Toxicol Sci. 2011 Nov;124(1):192-201. doi: 10.1093/toxsci/kfr221.

    -Tofighi R, Moors M, Bose R, Ibrahim WN, Ceccatelli S. Neural stem cells for developmental neurotoxicity studies. Methods Mol Biol. 2011;758:67-80. doi:10.1007/978-1-61779-170-3_5. PMID: 21815059.

    -Akanda N, Tofighi R, Brask J, Tamm C, Elinder F, Ceccatelli S. Voltage-dependent anion channels (VDAC) in the plasma membrane play a critical role in apoptosis in differentiated hippocampal neurons but not in neural stem cells. Cell Cycle. 2008 Oct;7(20):3225-34.

    -Tamm C, Zhivotovsky B, Ceccatelli S. Caspase-2 activation in neural stem cells undergoing oxidative stress-induced apoptosis. Apoptosis. 2008 Mar;13(3):354-63. doi: 10.1007/s10495-007-0172-7. PMID: 18181021.

    -Tamm C, Duckworth JK, Hermanson O, Ceccatelli S. Methylmercury inhibits differentiation of rat neural stem cells via Notch signalling. Neuroreport. 2008 Feb 12;19(3):339-43. doi: 10.1097/WNR.0b013e3282f50ca4. PMID: 18303578.

    -Tamm C, Sabri F, Ceccatelli S. Mitochondrial-mediated apoptosis in neural stem cells exposed to manganese. Toxicol Sci. 2008 Feb;101(2):310-20. doi:10.1093/toxsci/kfm267. Epub 2007 Oct 31. PMID: 17977900.

    -Tamm C, Duckworth J, Hermanson O, Ceccatelli S. High susceptibility of neural stem cells to methylmercury toxicity: effects on cell survival and neuronal differentiation. J Neurochem. 2006 Apr;97(1):69-78. doi:10.1111/j.1471-4159.2006.03718.x. Epub 2006 Mar 8.

    -Tamm C, Robertson JD, Sleeper E, Enoksson M, Emgård M, Orrenius S, Ceccatelli S. Differential regulation of the mitochondrial and death receptor pathways in neural stem cells. Eur J Neurosci. 2004 May;19(10):2613-21. doi:10.1111/j.0953-816X.2004.03391.x.

    -Ceccatelli S, Tamm C, Sleeper E, Orrenius S. Neural stem cells and cell death. Toxicol Lett. 2004 Apr 1;149(1-3):59-66.

    -Sleeper E, Tamm C, Frisén J, Zhivotovsky B, Orrenius S, Ceccatelli S. Cell death in adult neural stem cells. Cell Death Differ. 2002 Dec;9(12):1377-8. 

    We have shown that high levels of glucocorticoids (GC) induce epigenetic modifications in genes critical for the regulation of cell proliferation, differentiation, migration, senescence, ion channels, mitochondrial function, and redox states. In in vivo studies in rodents, we observed alterations in hippocampal neurogenesis in male mice exposed to GC in utero, which develop depression-like behavior in adulthood. The appearance of depression is preceded by long-lasting disturbances in circadian activity and alterations in the expression of clock genes. Interestingly, our clinical investigations show that abnormal circadian activity patterns are present in depressed patients as well and the type of pattern of activity predicts the response to therapy. I and my closest collaborator, Dr. Stefan Spulber, patented this knowledge in the USA (PCT/EP2015/070644) and founded Northern Light Diagnostics AB. 

    -Stefan Spulber, Sandra Ceccatelli, Yvonne Forsell. Individual pattens of activity predict the response to physical exercise as an intervention in mild to moderate depression. medRxiv 2024.02.12.24302721

    -Stefan Spulber, Frederik Elberling, Sandra Ceccatelli, Martin Gärde, Mikael Tiger, Johan Lundberg. Correlations between patterns of activity and the response to treatment yield distinct signatures for different antidepressive treatments. medRxiv 2023.09.29.23294935

    -Elberling F, Spulber S, Bose R, Keung HY, Ahola V, Zheng Z, Ceccatelli S. Sex Differences in Long-term Outcome of Prenatal Exposure to Excess Glucocorticoids-Implications for Development of Psychiatric Disorders. Mol Neurobiol. 2023 Dec;60(12):7346-7361. 

    -Spulber S, Elberling F, Svensson J, Tiger M, Ceccatelli S, Lundberg J. Patterns of activity correlate with symptom severity in major depressive disorder patients. Transl Psychiatry. 2022 Jun 2;12(1):226. doi:10.1038/s41398-022-01989-9.

    -Spulber S, Conti M, Elberling F, Raciti M, Borroto-Escuela DO, Fuxe K, Ceccatelli S. Desipramine restores the alterations in circadian entrainment induced by prenatal exposure to glucocorticoids. Transl Psychiatry. 2019 Oct 17;9(1):263. doi: 10.1038/s41398-019-0594-3.

    -Raciti M, Ong J, Weis L, Edoff K, Battagli C, Falk A, Ceccatelli S. Glucocorticoids alter neuronal differentiation of human neuroepithelial-like cells by inducing long-lasting changes in the reactive oxygen species balance. Neuropharmacology. 2016 Aug;107:422-431.

    -Spulber S, Conti M, DuPont C, Raciti M, Bose R, Onishchenko N, Ceccatelli S. Alterations in circadian entrainment precede the onset of depression-like behavior that does not respond to fluoxetine. Transl Psychiatry. 2015 Jul 14;5(7):e603. doi: 10.1038/tp.2015.94.

    -Bose R, Spulber S, Kilian P, Heldring N, Lönnerberg P, Johnsson A, Conti M, Hermanson O, Ceccatelli S. Tet3 mediates stable glucocorticoid-induced alterations in DNA methylation and Dnmt3a/Dkk1 expression in neural progenitors. Cell Death Dis. 2015 Jun 18;6(6):e1793. 

    -Bose R, Moors M, Tofighi R, Cascante A, Hermanson O, Ceccatelli S. Glucocorticoids induce long-lasting effects in neural stem cells resulting in senescence-related alterations. Cell Death Dis. 2010 Nov 4;1(11):e92. doi:10.1038/cddis.2010.60.

    Number of publications: 217; Discipline H-index: 78; Citations: 17, 696. (Research.com).

Articles

All other publications

Employments

  • Professor, Department of Neuroscience, Karolinska Institutet, 2008-

Leadership and responsibility assignments

  • Head of department, Ming Wai Lau Centre for Reparative Medicine, Karolinska Institutet, 2021-2023

News from KI

Events from KI