Artboard 2 copy 35Artboard 64 copy 13Artboard 2 copy 19Artboard 2 copy 31Artboard 64 copy 18Artboard 64 copy 10Artboard 64 copy 11Artboard 64 copy 15Artboard 64 copy 12Artboard 64 copy 13Artboard 64 copy 14Artboard 2 copy 34Artboard 64 copy 19Artboard 64 copy 16MinusArtboard 2 copy 44Artboard 2 copy 38Artboard 2 copy 36PlusArtboard 64 copy 17Artboard 2 copy 43Artboard 2 copy 45Artboard 2 copy 46Artboard 64 copy 16Artboard 64 copy 18Artboard 64 copy 19Artboard 64 copy 17

Maternal inhalation of carbon black nanoparticles induces neurodevelopmental changes in mouse offspring

Tidsskriftartikel - 2018

Resume

BACKGROUND: Engineered nanoparticles are smaller than 100 nm and designed to improve or creating even new physico-chemical properties. Consequently, toxicological properties of materials may change as size reaches the nm size-range. We examined outcomes related to the central nervous system in the offspring following maternal inhalation exposure to nanosized carbon black particles (Printex 90).

METHODS: Time-mated mice (NMRI) were exposed by inhalation, for 45 min/day to 0, 4.6 or 37 mg/m3 aerosolized carbon black on gestation days 4-18, i.e. for a total of 15 days. Outcomes included maternal lung inflammation (differential cell count in bronchoalveolar lavage fluid and Saa3 mRNA expression in lung tissue), offspring neurohistopathology and behaviour in the open field test.

RESULTS: Carbon black exposure did not cause lung inflammation in the exposed females, measured 11 or 28-29 days post-exposure. Glial fibrillary acidic protein (GFAP) expression levels were dose-dependently increased in astrocytes around blood vessels in the cerebral cortex and hippocampus in six weeks old offspring, indicative of reactive astrogliosis. Also enlarged lysosomal granules were observed in brain perivascular macrophages (PVMs) in the prenatally exposed offspring. The number of parvalbumin-positive interneurons and the expression levels of parvalbumin were decreased in the motor and prefrontal cortices at weaning and 120 days of age in the prenatally exposed offspring. In the open field test, behaviour was dose-dependently altered following maternal exposure to Printex 90, at 90 days of age. Prenatally exposed female offspring moved a longer total distance, and especially males spent significantly longer time in the central zone of the maze. In the offspring, the described effects were long-lasting as they were present at all time points investigated.

CONCLUSION: The present study reports for the first time that maternal inhalation exposure to Printex 90 carbon black induced dose-dependent denaturation of PVM and reactive astrocytes, similarly to the findings observed following maternal exposure to Printex 90 by airway instillation. Of note, some of the observed effects have striking similarities with those observed in mouse models of neurodevelopmental disorders.

Reference

Umezawa M, Onoda A, Korshunova I, Jensen ACØ, Koponen IK, Jensen KA, Khodosevich K, Vogel U, Hougaard KS. Maternal inhalation of carbon black nanoparticles induces neurodevelopmental changes in mouse offspring. Particle and Fibre Toxicology 2018;15.
doi: 10.1186/s12989-018-0272-2

Gå til Tidsskriftartikel