title: Minocycline ameliorates prenatal valproic acid induced autistic behaviour, biochemistry and blood brain barrier impairments in rats.
abstract: Autism is a neurodevelopment disorder. One percent worldwide population suffers with autism and males suffer more than females. Microglia plays an important role in neurodevelopment, neuropsychiatric and neurodegenerative disorders. The present study has been designed to investigate the role of minocycline in prenatal valproic acid induced autism in rats. Animals with prenatal valproic acid have reduced social interaction (three chamber social behaviour apparatus), spontaneous alteration (Y-Maze), exploratory activity (Hole board test), intestinal motility, serotonin levels (both in prefrontal cortex and ileum) and prefrontal cortex mitochondrial complex activity (complexes I, II, IV). Furthermore, prenatal valproic acid treated animals have shown an increase in locomotion (actophotometer), anxiety (elevated plus maze), brain oxidative stress (thiobarbituric acid reactive species, glutathione, catalase), nitrosative stress (nitrite/nitrate), inflammation (both in brain and ileum myeloperoxidase activity), calcium and blood brain barrier permeability. Treatment with minocycline significantly attenuated prenatal valproic acid induced reduction in social interaction, spontaneous alteration, exploratory activity intestinal motility, serotonin levels and prefrontal cortex mitochondrial complex activity. Furthermore, minocycline has also attenuated prenatal valproic acid induced increase in locomotion, anxiety, brain oxidative and nitrosative stress, inflammation, calcium and blood brain barrier permeability. Thus, it may be concluded that prenatal valproic acid has induced autistic behaviour, biochemistry and blood brain barrier impairment in animals, which were significantly attenuated by minocycline. Minocycline should be explored further for its therapeutic benefits in autism.
authors.affiliation: CNS Research Lab., Department of Pharmacology, School of Pharmacy, Bharat Institute of Technology, Partapur Bypass, Meerut, Uttar Pradesh, India. Electronic address: sharmaslab7@gmail.com.
authors.forename: Hariom
authors.initials: H
authors.lastname: Kumar
authors.affiliation: Department of Pharmacology, Amity Institute of Pharmacy, Amity University, Sector-125, Noida, Uttar Pradesh, India; CNS Pharmacology, Conscience Research, Pocket F-233, B, Dilshad Garden, Delhi 110095, India. Electronic address: drbhupeshresearch@gmail.com.
authors.forename: Bhupesh
authors.initials: B
authors.lastname: Sharma
mesh_terms: D000818:Animals; D001321:Autistic Disorder / Q000188:drug therapy* / Q000503:physiopathology; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002199:Capillary Permeability / Q000187:drug effects / Q000502:physiology; D002491:Central Nervous System Agents / Q000494:pharmacology*; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000187:drug effects; D005260:Female; D007422:Intestines / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D008911:Minocycline / Q000494:pharmacology*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009043:Motor Activity / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism; D012919:Social Behavior; D014635:Valproic Acid / Q000633:toxicity*
chemical_list: D002491:Central Nervous System Agents; D012701:Serotonin; D014635:Valproic Acid; D008911:Minocycline
keywords: Autism; Blood brain barrier permeability; Intestinal motility; Microglia inhibition; Mitochondrial complex; Serotonin