A proteomic approach to investigate enhanced responsiveness in rechallenged adult rats prenatally exposed to lindane

• Published in: Neurotoxicology (Park Forest South) 2019-09, Vol.74, p.184-195
• Main Authors: Srivastava, Ankita, Srivastava, Ankur Kumar, Mishra, Manisha, Shankar, Jai, Agrahari, Anita, Kamthan, Mohan, Singh, Pradhyumna K., Yadav, Sanjay, Parmar, Devendra
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; Axons - drug effects; Behavior, Animal - drug effects; Brain; Brain Chemistry - drug effects; Cognitive ability; Disruption; DNA fragmentation; Electrophoresis; Energy metabolism; Energy Metabolism - drug effects; Exposure; Female; Gel electrophoresis; Gestation; Hexachlorocyclohexane - toxicity; Hippocampus - drug effects; Hippocampus - growth & development; Insecticides - toxicity; Lindane; Male; Mitochondria; Mitochondria - drug effects; Mitochondria - metabolism; Nerve Tissue Proteins - biosynthesis; Nerve Tissue Proteins - genetics; Nervous system; Neurodegeneration; Neurotoxicity Syndromes - pathology; Neurotoxicity Syndromes - psychology; Offspring; Oxidative stress; Oxidative Stress - drug effects; Pregnancy; Prenatal experience; Prenatal exposure; Prenatal Exposure Delayed Effects; Proteasome Endopeptidase Complex - drug effects; Proteasomes; Proteins; Proteomic; Proteomics - methods; Rat; Rats; Rats, Wistar; Rechallenge; Substantia nigra; Substantia Nigra - drug effects; Substantia Nigra - growth & development; Ubiquitin; Western blotting
• ISSN: 0161-813X; 1872-9711
• DOI: 10.1016/j.neuro.2019.07.004

[Display omitted] •Rechallenge of lindane induces different expression of proteins in brain regions of prenatally exposed offspring.•TEM analysis demonstrated apoptotic nuclei and necrotic structures in Hi and SNi of rechallenged offspring.•The data suggests increased vulnerability to neurodegeneration in rechallenged offspring. Proteomic analysis was carried out in substantia nigra (SNi) and hippocampus (Hi) isolated from rat offspring born to mothers exposed to lindane (orally; 0.25 mg/kg) from gestation day 5 (GD5) to GD 21 and subsequently rechallenged (orally; 2.5 mg/kg X 21 days) at adulthood (12 weeks). 2D gel electrophoresis revealed no significant differences in the expression of proteins in brain regions isolated from prenatally exposed offspring at adulthood. Significantly greater magnitude of alterations was observed in the expression of proteins related to mitochondrial and energy metabolism, ubiquitin-proteasome pathway, structural and axonal growth leading to increased oxidative stress in Hi and SNi isolated from rechallenged offspring when compared to control offspring treated postnatally with lindane. Western blotting and DNA laddering showed a greater magnitude of increase in apoptosis in the Hi and SNi of rechallenged offspring. Ultrastructural analysis demonstrated disrupted mitochondrial integrity, synaptic disruption and necrotic structures in the brain region of rechallenged offspring. Neurobehavioral studies also demonstrated a greater magnitude of alterations in cognitive and motor functions in rechallenged rats. The data suggest that prenatal exposure of lindane induces persistent molecular changes in the nervous system of offspring which are unmasked leading to neurodegeneration following rechallenge at adulthood.