ABSTRACT
Title
Central effects of a local inflammation on three commonly used mouse strains with a different anxious phenotype
Authors
C. Benatti 1, S. Alboni 1, C. Montanari 1, F. Tascedda 1, N. Brunello 1, J.M.C. Blom 2
1 Department of Biomedical Sciences; University of Modena and Reggio Emilia Via Campi 287, 41100 Modena, Italy
2 Department of Paediatrics; University Hospital of Modena Via del Pozzo 71, 41100 Modena, Italy
1 Department of Biomedical Sciences; University of Modena and Reggio Emilia Via Campi 287, 41100 Modena, Italy
2 Department of Paediatrics; University Hospital of Modena Via del Pozzo 71, 41100 Modena, Italy
Abstract
Rodents represent a valuable resource to enhance our understanding of biological functions, drug actions as well as ethiopathology of several human diseases. However, in recent years the genetic background of the animals used in neuropharmacology studies has been shown to interfere with the observed outcomes, in fact each rodent strain is characterized by its unique pattern of behavior and their genetic inheritance influences behavioral traits such as sensitivity to pain and stressors as well as anxiety-related traits and depression related behaviours [1].
The first aim of our study was to better characterize three commonly used mice strains. In doing so, we evaluated anxious behavior on an elevated plus maze (EPM) and assessed heat nociception to a radiant heat source after a subplantar injection of either saline or the inflammatory agent Complete Freund’s Adjuvant (CFA).
Second aim of our research was to look for possible inter-strain molecular differences in the hippocampus. Using Real Time PCR, we investigated expression levels of BDNF (Brain Derived Neurotrophic Factor) mRNA in hippocampus of animals treated with either saline or CFA.
An outbred strain (CD1), an inbred strains (C57BL/6J) commonly used for generating genetically modified mice and for conventional experiments in pharmacology and toxicology and an hybrid strain (B6C3F1) have been selected for this experiment.
A 5 minute session on an EPM was performed at 11 weeks of age on adult male mice. At twelve weeks of age thermal nociception to a radiant heat source was measured; paw withdrawal latency (PWL) of each animal was tested 24h after an unilateral injection with either 100 μL of CFA or saline in the left hind paw. 24 hrs after measuring PWL, animals were sacrificed.
Our behavioral data showed that CD1, C57BL/6J and B6C3F1 differed when tested on an EPM with respect to anxiety related behavioral parameters. In particular, B6C3F1 mice displayed the more anxious phenotype with respect to C57BL/6J or CD1animals, with the latter being the less anxious strain.
When considering the nociceptive thresholds, animals treated with CFA were hyperalgesic with respect to saline exposed animals, irrespective of their strain. However, genetic background did not affect behavioural reactivity to a radiant heat source with or without an ongoing inflammation.
Real Time results showed a significant decrease in BDNF mRNA levels in CD1 animals treated with CFA with respect to their saline exposed counterparts, while no effect was observed in C57BL/6J and B6C3F1 animals. B6C3F1 animals treated with saline presented lower hippocampal levels of BDNF with respect to their CD1 counterparts exposed to saline.
Our data indicate that the more anxious phenotype of B6C3F1 hybrid animals is correlated to lower levels of BDNF mRNA in the hippocampus with respect to outbred CD1 animals and that with respect to BDNF no correlation seems to exists when comparing anxious phenotype to heat nociception.
Our finding highlights the need to fully characterize animal models to get a better grip on the behavioral outcome of complex gene environment interaction.
[1] C. Benatti, S. Alboni, G. Capone, D. Corsini, F.Caggia, N. Brunello, F. Tascedda, J.M.C. Blom. Early neonatal inflammation affects adult pain reactivity and anxiety related traits in mice: genetic background counts. International Journal of Developmental Neuroscience, Volume 27, Issue 7, November 2009, Pages 661-668
The first aim of our study was to better characterize three commonly used mice strains. In doing so, we evaluated anxious behavior on an elevated plus maze (EPM) and assessed heat nociception to a radiant heat source after a subplantar injection of either saline or the inflammatory agent Complete Freund’s Adjuvant (CFA).
Second aim of our research was to look for possible inter-strain molecular differences in the hippocampus. Using Real Time PCR, we investigated expression levels of BDNF (Brain Derived Neurotrophic Factor) mRNA in hippocampus of animals treated with either saline or CFA.
An outbred strain (CD1), an inbred strains (C57BL/6J) commonly used for generating genetically modified mice and for conventional experiments in pharmacology and toxicology and an hybrid strain (B6C3F1) have been selected for this experiment.
A 5 minute session on an EPM was performed at 11 weeks of age on adult male mice. At twelve weeks of age thermal nociception to a radiant heat source was measured; paw withdrawal latency (PWL) of each animal was tested 24h after an unilateral injection with either 100 μL of CFA or saline in the left hind paw. 24 hrs after measuring PWL, animals were sacrificed.
Our behavioral data showed that CD1, C57BL/6J and B6C3F1 differed when tested on an EPM with respect to anxiety related behavioral parameters. In particular, B6C3F1 mice displayed the more anxious phenotype with respect to C57BL/6J or CD1animals, with the latter being the less anxious strain.
When considering the nociceptive thresholds, animals treated with CFA were hyperalgesic with respect to saline exposed animals, irrespective of their strain. However, genetic background did not affect behavioural reactivity to a radiant heat source with or without an ongoing inflammation.
Real Time results showed a significant decrease in BDNF mRNA levels in CD1 animals treated with CFA with respect to their saline exposed counterparts, while no effect was observed in C57BL/6J and B6C3F1 animals. B6C3F1 animals treated with saline presented lower hippocampal levels of BDNF with respect to their CD1 counterparts exposed to saline.
Our data indicate that the more anxious phenotype of B6C3F1 hybrid animals is correlated to lower levels of BDNF mRNA in the hippocampus with respect to outbred CD1 animals and that with respect to BDNF no correlation seems to exists when comparing anxious phenotype to heat nociception.
Our finding highlights the need to fully characterize animal models to get a better grip on the behavioral outcome of complex gene environment interaction.
[1] C. Benatti, S. Alboni, G. Capone, D. Corsini, F.Caggia, N. Brunello, F. Tascedda, J.M.C. Blom. Early neonatal inflammation affects adult pain reactivity and anxiety related traits in mice: genetic background counts. International Journal of Developmental Neuroscience, Volume 27, Issue 7, November 2009, Pages 661-668