Profiles

Anna Forsby

Anna Forsby

Docent

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Works at Department of Biochemistry and Biophysics
Telephone 08-16 41 69
Email anna.forsby@dbb.su.se
Visiting address Svante Arrhenius väg 16
Room M 448
Postal address Institutionen för biokemi och biofysik 106 91 Stockholm

Research

Cellular Neurotoxicity and Nociception

The main interest of the research within the group is to study mechanisms for chemically induced acute and subchronic neurotoxicity by using different neuronal cell models. The usefulness of the cell models for risk assessment is evaluated by integrating in vitro data derived from the cell models with historic in vivo data from rat and clinical observations from exposed human in predictions models. Furthermore, mechanisms for chemically induced nociception are studied in a recombinant neuronal cell model expressing the Transient Receptor Potential Vanilloid (TRPV) ion channels.

 

Research Projects

 

1. Neurotoxicity determined in vitro

 

The development of alternative methods for studies of neurotoxicological mechanisms has gained great success during the past years. One approach is to use cell lines of neuronal origin, which under certain culture conditions can develop into highly differentiated cells expressing specific neuronal features.
 
Human neuroblastoma SH-SY5Y cells can be used to study axonopathy, which can be induced by neurotoxic chemicals (e.g. acrylamide and gliotoxin) or increased glucose concentrations. The model can also be used to study toxic insult to neurons during development, as exemplified in a study of neurite outgrowth after exposure to low dose γ-irradiation. The SH-SY5Y cells are also useful for studies on acetylcholine receptor signaling and esterase activity. These endpoints, together with noradrenalin uptake, cell membrane potential and voltage operated calcium channel function have been evaluated as neuronal markers for acute neurotoxicity in the EU-financed project ACuteTox, www.acutetox.eu.
 
The neural progenitor cell line C17.2 is derived from neonatal mouse cerebellum and immortalized by v-myc transfection. The multipotent progenitor cells can differentiate into neurons and astrocytes after 8 days in culture in serum-free medium which is supplemented with neurotrophic factors. The potential of the mixed cell culture as a substitute to primary embryonic rat brain cell cultures is investigated. The neuronal and glia phenotypes are now evaluated biochemically and functionally. Markers for cellular stress and cell-specific markers for neurons and astrocyte are analyzed by quantitative real time PCR after exposure to ACuteTox reference chemicals.
 

2. The NociOcular test: TRPV1-expressing cells as a model for eye-irritation

 

Draize’s eye irritation test is required as the principal test method for classification of eye irritation. The Draize test has been criticized because of its cruelty to the animals and the subjective judgment of eye toxicity. Large efforts have resulted in several alternative methods for estimation of ocular toxicity. However, none of these take sensory stimulation of nerves into consideration; a feature which should be correlated with mild irritation. We have developed a promising cell model, which may be useful for detection of mild eye irritation. SH-SY5Y cells are transfected with the Transient Receptor Potential Vanilloid, type 1 (TRPV1) ion channel. TRPV1 can be activated by nociceptive (pain-inducing) compounds, acidic pH and noxious heat. Our research has shown that anionic linear aliphatic detergents, which are known to induce severe ocular pain and eye irritation, also activate the receptor. There is also a strong correlation between the eye stinging potential of personal hygiene products and the lowest effective concentration determined in the NociOcular test.
 

PhD student

Kristina Attoff
 

Selected publications:

 

Bajinskis A., Lindegren H., Johansson L., Harms-Ringdahl M. and Forsby A. (2011). Low dose/dose rate γ-radiation depresses neuronal differentiation and alters protein expression profiles. Radiation Research 175(2):185-92.
 
Gustafsson H, Runesson J., Lundqvist J., Lindegren H., Axelsson V. and Forsby A. (2010). Neurofunctional endpoints assessed in human neuroblastoma SH-SY5Y cells for estimation of acute systemic toxicity. Toxicol Appl Pharmacol. 245(2):191-202.
 
Forsby A., Bal-Price A., Camins A., Coecke S., Fabre, N., Gustafsson H., Honegger P., Kinsner-Ovaskainen A., Pallas M., Rimbau V., Rodríguez-Farré E., Suñol C., Vericat J.A. and Zurich, M.G.(2009). Neuronal in vitro models for the estimation of acute systemic toxicity. Toxicology In Vitro, 23(8); 1564-9.
 
Clemedson C., Kolman A. and Forsby A. (2007). Integrated acute systemic toxicity project (Acutetox) for optimization and validation of alternative in vitro tests. ATLA, 35(1): 33-38.
 
Forsby A. and Blaauboer B. (2007). Integration of In Vitro Neurotoxicity Data with Biokinetic Modeling for the Estimation of In Vivo Neurotoxicity. Human & Experimental Toxicology, 26(4): 333-338.
 
Nordin Andersson M., Walum E., Kjellstrand P. and Forsby A. (2003). Acrylamide-induced effects on general and neurospecific cellular functions during exposure and recovery. Cell Biol Toxicol, 19, 43-51.
 
DeJongh J., Nordin Andersson M., Ploeger B.A. and Forsby A. (1999). Estimation of systemic toxicity of acrylamide by integration of in vitro toxicity data with kinetic simulations. Toxicology and Applied Pharmacology, 13, 261-268.
 
DeJongh J., Forsby A., Houston B.J., Beckman M., Combes R. and Blaauboer BJ. (1999). An integrated approach to the prediction of systemic toxicity using computer-based biokinetic models and biological in vitro test methods: overview of a prevalidation study based on the ECITTS project. Toxicology in Vitro, 13, 549-554.
 
WenehedV., SolyakovA., Thylin I., Häggblom P. and Forsby A. (2003). Cytotoxic response of Aspergillus fumigatus-produced mycotoxins in broth, maize and commercial animal feed substrates. Food Chem Toxicol, 41, 395-403.
 
Lilja J. and Forsby A. (2004). Development of a sensory neuronal method for the estimation of mild eye irritation. ATLA. 32, 339-343.
 
Lilja J., Lindegren H. and Forsby A. (2007). Surfactant-Induced TRPV1 Activity A Novel Mechanism for Eye Irritation? Toxicol Sci . Sep;99(1):174-80.
 
Lindegren H., Mogren H., El Andaloussi-Lilja J., Lundqvist J., and Forsby A. (2009). Anionic linear aliphatic surfactants activate the TRPV1: A possible endpoint for estimation of detergent-induced eye nociception? Toxicology In Vitro, 23(8); 1472-6.
 
EL Andaloussi-Lilja L., Lundqvist J. and Forsby A. (2009). TRPV1 expression and activity during retinoic acid-induced neuronal differentiation. Neurochemistry International. 55, 768-774.
 
Lilja J., Laulund F. and Forsby A. (2007) Insulin and insulin like growth factor type-I up-regulate vanilloid receptor-1 (TRPV1) in stably TRPV1-expressing SH-SY5Y neuroblastoma cells. J. Neurosci. Res. 85(7):1413-1419
 
Gustafsson H., Söderdahl T., Jönsson G., Bratteng J.-O. and Forsby A. (2004) Insulin-like growth factor type 1 prevents hyperglycemia-induced uncoupling protein 3 down-regulation and oxidative stress. J Neurosci Res. 15; 77(2):285-91.
 
Gustafsson H., Adamsson L., Hedander J., Walum E. and Forsby A. (2001). Insulin-like growth factor type I up-regulates uncoupling protein 3. Biochem. Biophys. Research. Comm., 287, 1105-1111.
 
Gustafsson H. Tamm C. and Forsby A. (2004). Signalling pathways for insulin-like growth factor type 1-mediated expression of uncoupling protein 3. J. Neurochem, 88, 462-468.
 
Axelsson V., Pirkkannen K. and Forsby A. (2006). Glutathione intensifies the cytotoxic effects of gliotoxin in human neuroblastoma SH-SY5Y cells. Cell Biol Toxicol. 22, 127-136.
 
Axelsson V., Holback S., Sjögren M., Gustafsson H. and Forsby A. (2006). Gliotoxin induces caspase-dependent neurite degeneration and calpain-mediated general cytotoxicity in differentiated human neuroblastoma SH-SY5Y cells. BBRC, 7;345(3), 1068-74.

Last updated: April 24, 2018

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