LAUSR

Trace elements such as copper (Cu) and arsenic (As) are two of the major contaminants and well-known inducers of cognitive deficits and neurobehavioral changes. This study evaluated the immunotoxicity of their individual or combined exposure on different brain regions in chickens. Consequently, nuclear damage and organelle lesions, especially mitochondria were observed under Cu or/and As stress, in which positive regulation of key proteins, dynamin-related protein 1 (Drp1), Cytochrome C (Cyt c), BCL2-associated X (Bax), Caspases 3 and P53 was detected by qRCR and Western blot analyses, indicating disturbed mitochondrial dynamic equilibrium and apoptosis execution. In addition, qRCR analysis confirmed the involvement of cytokines secreted by different populations of helper T cells, indicative of cellular immunity. Gene expression studies showed marked up regulation of Th1/Th17 cytokines along with heat shock protein (HSP) 70, a synergism was noted in co-administration group. Interesting, lower apoptosis index was noted in brainstem compared to cerebrum and cerebellum. An intense immunosuppression and heat shock response against Cu or/and As was also seen in cerebrum and cerebellum but not in brainstem. In conclusion, our study suggests a synergistic neurotoxicity in chickens under Cu and As exposure. These findings provide a basic understanding of mitochondrial abnormality-initiated neuropathology in response to environmental pollutant mixtures, suggesting an adaptive response to the frangibility of the central nerve system.