Lactational exposure of mice to low levels of non-dioxin-like polychlorinated biphenyls increases susceptibility to neuronal stress at a mature age
Introduction
Early-life exposure to certain natural and synthetic chemicals may increase the risk of neurodegenerative and other diseases later in life (Spencer, 1987, Landrigan et al., 2005, Kisby and Spencer, 2011, Fox et al., 2012). The increase in childhood pathologies, such as hyperactivity or memory alterations, and the occurrence of neurodegenerative diseases such as Alzheimer's and Parkinson's diseases in the elderly, may be due in part to the early chronic exposure of pollutants and their related impacts in early stages of life (Corrigan et al., 2000, Bihaqi et al., 2011, Bihaqi and Zawia, 2013, Bihaqi et al., 2014a, Medehouenou et al., 2011, Medehouenou et al., 2014, Jurewicz et al., 2013, Grandjean and Landrigan, 2014). Fetuses and newborn babies are particularly exposed to chemicals during their development via maternal transfer, when the central nervous system (CNS) is still in maturation. These young individuals are thought to be more susceptible than adults to environmental insults (Weiss and Landrigan, 2000).
Polychlorinated biphenyls (PCBs) are ubiquitous and persistent organic compounds that accumulate in lipid tissues of living organisms (Ogura, 2004, Hornbuckle et al., 2006). Upon ingestion, they can be stored in fatty tissues, including the brain (Dewailly et al., 1999), and it has been shown that during the perinatal stage, these xenobiotics may cross the blood–brain barrier (Kunisue et al., 2007, Montie et al., 2009). Numerous epidemiological investigations have linked PCB levels detected in human biological tissues to neurocognitive and neurobehavioral deficits in older adults (Hatcher-Martin et al., 2012, Medehouenou et al., 2014, Richardson et al., 2014), suggesting potential neurotoxicity in humans (Fonnum and Mariussen, 2009). Experimental animal and human studies have proposed that exposure to PCBs increases the risk of neurodegenerative disease (Caudle et al., 2006, Petersen et al., 2008, Hatcher-Martin et al., 2012).
Exposure to non-dioxin-like (NDL) PCBs has been shown to affect CNS development. We found previously a persistent anxious behavior from postnatal day (PND) 0 up to PND 21 in young and adult mice treated with the sum of six indicator NDL-PCBs through mother's milk during lactation (Elnar et al., 2012). Here, we ask whether such an early exposure could lead to adverse effects in cognition later in adulthood. We provide evidence for increased neuronal susceptibility to amyloid stress induced by intracerebroventricular (icv) injection of neurotoxic soluble oligomers of amyloid-beta (Aβ) peptide.
Section snippets
Lactational exposure to Σ6 NDL-PCBs
Animal studies were performed in accordance with the European Union (Directive 2010/63/EU) and approved by the local research ethics committee (CELMEA-2013-0010).
Animal treatment, as well as composition (PCBs 28, 52, 101, 138, 153 and 180, purity > 99.5%, Sigma–Aldrich) and preparation of the stock solution of Σ6 NDL-PCBs have been detailed previously (Elnar et al., 2012). Briefly, 50 sexually mature female and 40 male Swiss albino mice (OF 1, Charles River, France) aged 9 weeks (30–40 g body
Effects of early PCB exposure on cognitive capacities
These tests were conducted to determine whether early lactational exposure to Σ6 NDL-PCBs at a low level could affect learning and memory capacities at a mature age.
Discussion
Whereas developmental exposure to lead (Pb) is reported to induce cognitive impairments, to increase the expression of the Aβ precursor protein as well as Aβ levels, and to promote neurodegeneration in old age (Wu et al., 2008, Huang et al., 2011, Bihaqi and Zawia, 2013, Bihaqi et al., 2014a, Bihaqi et al., 2014b, Liu et al., 2014), little is known about the effects of early life exposure to PCBs on brain susceptibility to amyloid stress.
The aim of this study was to investigate the long-term
Conclusion
This preliminary study shows that, at maturity, early-life lactational exposure to very low levels of Σ6 NDL-PCBs increases brain susceptibility to amyloid stress and impaired long-term memory.
Conflict of interest statement
The authors have no conflict of interest to declare.
Acknowledgments
Nicolas Fischer is thanked for his skilled technical assistance in brain injection. Financial support was provided by the Agence Nationale de la Recherche (ANR-11-CESA-000) and the Région Lorraine. A. Allouche was supported by thesis fellowships from the University of Damascus, Damascus, Syria.
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These authors contributed equally to this study.