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Chronic infection of Toxoplasma gondii downregulates miR-132 expression in multiple brain regions in a sex-dependent manner

Published online by Cambridge University Press:  29 October 2014

YE LI ,
GEETHA KANNAN ,
MIKHAIL V. PLETNIKOV ,
ROBERT H. YOLKEN  and
JIANCHUN XIAO
YE LI
Affiliation:
Stanley Division of Developmental Neurovirology, Department of Pediatrics, Johns Hopkins School of Medicine, Baltimore, Maryland 21287, USA Department of Psychiatry, Renmin Hospital, Wuhan University, Wuhan, PR China
GEETHA KANNAN
Affiliation:
Division of Neurobiology, Department of Psychiatry, Johns Hopkins School of Medicine, Baltimore, Maryland 21287, USA
MIKHAIL V. PLETNIKOV
Affiliation:
Division of Neurobiology, Department of Psychiatry, Johns Hopkins School of Medicine, Baltimore, Maryland 21287, USA
ROBERT H. YOLKEN
Affiliation:
Stanley Division of Developmental Neurovirology, Department of Pediatrics, Johns Hopkins School of Medicine, Baltimore, Maryland 21287, USA
JIANCHUN XIAO*
Affiliation:
Stanley Division of Developmental Neurovirology, Department of Pediatrics, Johns Hopkins School of Medicine, Baltimore, Maryland 21287, USA
*
*Corresponding author: Stanley Division of Developmental Neurovirology, Department of Pediatrics, Johns Hopkins School of Medicine, Baltimore, Maryland 21287, USA. E-mail: [email protected]
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Summary

MicroRNA-132 (miR-132) has been demonstrated to affect multiple neuronal functions and its dysregulation is linked to several neurological disorders. We previously showed that acute Toxoplasma gondii infection induces miR-132 expression both in vitro and in vivo. To investigate the impact of chronic infection on miR-132, we infected mice with T. gondii PRU strain and performed assessment 5 months later in six brain regions (cortex, hypothalamus, striatum, cerebellum, olfactory bulb and hippocampus) by qPCR. We found that while acute infection of T. gondii increases the expression of miR-132, chronic infection has the opposite effect. The effect varied amongst different regions of the brain and presented in a sex-dependent manner, with females exhibiting more susceptibility than males. MiR-132 and brain-derived neurotrophic factor (BDNF, an inducer of miR-132) were not co-varies in the brain areas of infected mice. T. gondii DNA/RNA was found in all tested brain regions and a selective tropism towards the hippocampus, based on bradyzoite density, was observed in both males and females. However, the expressions of miR-132 or BDNF were poorly reflected by the density of T. gondii in brain areas. Our findings highlight the importance of investigating the miR-132-mediated neuronal function in mice infected with T. gondii.

Keywords

Toxoplasma gondiimiR-132BDNFbradyzoite densityhippocampushost sex
Type
Research Article
Information
Parasitology , Volume 142 , Issue 4 , April 2015 , pp. 623 - 632
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Copyright
Copyright © Cambridge University Press 2014 

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References

REFERENCES

Airan, R. D., Meltzer, L. A., Roy, M., Gong, Y., Chen, H. and Deisseroth, K. (2007). High-speed imaging reveals neurophysiological links to behavior in an animal model of depression. Science 317, 819–823.CrossRefGoogle ScholarPubMed
Benraiss, A., Chmielnicki, E., Lerner, K., Roh, D. and Goldman, S. A. (2001). Adenoviral brain-derived neurotrophic factor induces both neostriatal and olfactory neuronal recruitment from endogenous progenitor cells in the adult forebrain. The Journal of Neuroscience 21, 6718–6731.Google Scholar
Berenreiterová, M., Flegr, J., Kuběna, A. A. and Němec, P. (2011). The distribution of Toxoplasma gondii cysts in the brain of a mouse with latent toxoplasmosis: implications for the behavioral manipulation hypothesis. PLoS ONE 6, e28925.Google Scholar
Gulinello, M., Acquarone, M., Kim, J. H., Spray, D. C., Barbosa, H. S., Sellers, R., Tanowitz, H. B. and Weiss, L. M. (2010). Acquired infection with Toxoplasma gondii in adult mice results in sensorimotor deficits but normal cognitive behavior despite widespread brain pathology. Microbes and Infection 12, 528–537.Google Scholar
Hansen, K. F., Sakamoto, K., Wayman, G. A., Impey, S. and Obrietan, K. (2010). Transgenic miR132 alters neuronal spine density and impairs novel object recognition memory. PLoS ONE 5, e15497.Google Scholar
Hansen, K. F., Karelina, K., Sakamoto, K., Wayman, G. A., Impey, S. and Obrietan, K. (2013). miRNA-132: a dynamic regulator of cognitive capacity. Brain Structure and Function 218, 817–831.CrossRefGoogle ScholarPubMed
Haroon, F., Händel, U., Angenstein, F., Goldschmidt, J., Kreutzmann, P., Lison, H., Fischer, K. D., Scheich, H., Wetzel, W., Schlüter, D. and Budinger, E. (2012). Toxoplasma gondii actively inhibits neuronal function in chronically infected mice. PLoS One 7, e35516.CrossRefGoogle ScholarPubMed
Hermes, G., Ajioka, J. W., Kelly, K. A., Mui, E., Roberts, F., Kasza, K., Mayr, T., Kirisits, M. J., Wollmann, R., Ferguson, D. J., Roberts, C. W., Hwang, J. H., Trendler, T., Kennan, R. P., Suzuki, Y., Reardon, C., Hickey, W. F., Chen, L. and McLeod, R. (2008). Neurological and behavioral abnormalities, ventricular dilatation, altered cellular functions, inflammation, and neuronal injury in brains of mice due to common, persistent, parasitic infection. Journal of Neuroinflammation 5, 48.Google Scholar
Hourez, R., Servais, L., Orduz, D., Gall, D., Millard, I., de Kerchove d'Exaerde, A., Cheron, G., Orr, H. T., Pandolfo, M. and Schiffmann, S. N. (2011). Aminopyridines correct early dysfunction and delay neurodegeneration in a mouse model of spinocerebellar ataxia type 1. The Journal of Neuroscience 31, 11795–11807.CrossRefGoogle Scholar
Ingram, W. M., Goodrich, L. M., Robey, E. A., Eisen, M. B. (2013). Mice infected with low-virulence strains of Toxoplasma gondii lose their innate aversion to cat urine, even after extensive parasite clearance. PLoS One 8, e75246.Google Scholar
Lambert, T. J., Storm, D. R. and Sullivan, J. M. (2010). MicroRNA132 modulates short-term synaptic plasticity but not basal release probability in hippocampal neurons. PLoS ONE 5, e15182.Google Scholar
Lazarov, O., Robinson, J., Tang, Y. P., Hairston, I. S., Korade-Mirnics, Z., Lee, V. M., Hersh, L. B., Sapolsky, R. M., Mirnics, K. and Sisodia, S. S. (2005). Environmental enrichment reduces Abeta levels and amyloid deposition in transgenic mice. Cell 120, 701–713.Google Scholar
Lindová, J., Kubena, A. A., Sturcová, H., Krivohlavá, R., Novotná, M., Rubesová, A., Havlícek, J., Kodym, P. and Flegr, J. (2010). Pattern of money allocation in experimental games supports the stress hypothesis of gender differences in Toxoplasma gondii-induced behavioural changes. Folia Parasitologica (Praha) 57, 136–142.Google Scholar
Magill, S. T., Cambronne, X. A., Luikart, B. W., Lioy, D. T., Leighton, B. H., Westbrook, G. L., Mandel, G. and Goodman, R. H. (2010). microRNA-132 regulates dendritic growth and arborization of newborn neurons in the adult hippocampus. Proceedings of the National Academy of Sciences of the USA 107, 20382–20387.Google Scholar
McHugh, T. J., Jones, M. W., Quinn, J. J., Balthasar, N., Coppari, R., Elmquist, J. K., Lowell, B. B., Fanselow, M. S., Wilson, M. A. and Tonegawa, S. (2007). Dentate gyrus NMDA receptors mediate rapid pattern separation in the hippocampal network. Science 317, 94–99.CrossRefGoogle ScholarPubMed
Miller, B. H., Zeier, Z., Xi, L., Lanz, T. A., Deng, S., Strathmann, J., Willoughby, D., Kenny, P. J., Elsworth, J. D., Lawrence, M. S., Roth, R. H., Edbauer, D., Kleiman, R. J. and Wahlestedt, C. (2012). MicroRNA-132 dysregulation in schizophrenia has implications for both neurodevelopment and adult brain function. Proceedings of the National Academy of Sciences of the USA 109, 3125–3130.Google Scholar
Monje, M. L., Toda, H. and Palmer, T. D. (2003). Inflammatory blockade restores adult hippocampal neurogenesis. Science 302, 1760–1765.Google Scholar
Remenyi, J., Hunter, C. J., Cole, C., Ando, H., Impey, S., Monk, C. E., Martin, K. J., Barton, G. J., Hutvagner, G. and Arthur, J. S. (2010). Regulation of the miR-212/132 locus by MSK1 and CREB in response to neurotrophins. The Biochemical Journal 428, 281–291.Google Scholar
Roberts, C. W., Cruickshank, S. M. and Alexander, J. (1995). Sex-determined resistance to Toxoplasma gondii is associated with temporal differences in cytokine production. Infection and Immunity 63, 2549–2555.Google Scholar
Takahashi, M., Ishikawa, K., Sato, N., Obayashi, M., Niimi, Y., Ishiguro, T., Yamada, M., Toyoshima, Y., Takahashi, H., Kato, T., Takao, M., Murayama, S., Mori, O., Eishi, Y. and Mizusawa, H. (2012). Reduced brain-derived neurotrophic factor (BDNF) mRNA expression and presence of BDNF-immunoreactive granules in the spinocerebellar ataxia type 6 (SCA6) cerebellum. Neuropathology 32, 595–603.Google Scholar
Tomita, T., Bzik, D. J., Ma, Y. F., Fox, B. A., Markillie, L. M., Taylor, R. C., Kim, K. and Weiss, L. M. (2013). The Toxoplasma gondii cyst wall protein CST1 is critical for cyst wall integrity and promotes bradyzoite persistence. PLoS Pathogens 9, e1003823.Google Scholar
Ueno, A., Dautu, G., Munyaka, B., Carmen, G., Kobayashi, Y. and Igarashi, M. (2009). Toxoplasma gondii: identification and characterization of bradyzoite-specific deoxyribose phosphate aldolase-like gene (TgDPA). Experimental Parasitology 121, 55–63.Google Scholar
Vyas, A., Kim, S. K., Giacomini, N., Boothroyd, J. C. and Sapolsky, R. M. (2007). Behavioral changes induced by Toxoplasma infection of rodents are highly specific to aversion of cat odors. Proceedings of the National Academy of Sciences of the USA 104, 6442–6447.Google Scholar
Wanet, A., Tacheny, A., Arnould, T. and Renard, P. (2012). miR-212/132 expression and functions: within and beyond the neuronal compartment. Nucleic Acids Research 40, 4742–4753.Google Scholar
Wang, R. Y., Phang, R. Z., Hsu, P. H., Wang, W. H., Huang, H. T. and Liu, I. Y. (2013). In vivo knockdown of hippocampal miR-132 expression impairs memory acquisition of trace fear conditioning. Hippocampus 23, 625–633.CrossRefGoogle ScholarPubMed
Wibrand, K., Panja, D., Tiron, A., Ofte, M. L., Skaftnesmo, K. O., Lee, C. S., Pena, J. T., Tuschl, T. and Bramham, C. R. (2010). Differential regulation of mature and precursor microRNA expression by NMDA and metabotropic glutamate receptor activation during LTP in the adult dentate gyrus in vivo . European Journal of Neuroscience 31, 636–645.Google Scholar
Xiao, J., Jones-Brando, L., Talbot, C. C. Jr. and Yolken, R. H. (2011). Differential effects of three canonical Toxoplasma strains on gene expression in human neuroepithelial cells. Infection and Immunity 79, 1363–1373.Google Scholar
Xiao, J., Kannan, G., Jones-Brando, L., Brannock, C., Krasnova, I. N., Cadet, J. L., Pletnikov, M. and Yolken, R. H. (2012). Sex-specific changes in gene expression and behavior induced by chronic Toxoplasma infection in mice. Neuroscience 206, 39–48.Google Scholar
Xiao, J., Li, Y., Prandovszky, E., Karuppagounder, S. S., Talbot, C. C. Jr., Dawson, V. L., Dawson, T. M. and Yolken, R. H. (2014). MicroRNA-132 dysregulation in Toxoplasma gondii infection has implications for dopamine signaling pathway. Neuroscience 268, 128–138.Google Scholar