PPAR-Alpha Agonists as Novel Antiepileptic Drugs: Preclinical Findings
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{"title"=>"PPAR-Alpha Agonists as Novel Antiepileptic Drugs: Preclinical Findings", "type"=>"journal", "authors"=>[{"first_name"=>"Monica", "last_name"=>"Puligheddu", "scopus_author_id"=>"6602663838"}, {"first_name"=>"Giuliano", "last_name"=>"Pillolla", "scopus_author_id"=>"13605492200"}, {"first_name"=>"Miriam", "last_name"=>"Melis", "scopus_author_id"=>"7102493419"}, {"first_name"=>"Salvatore", "last_name"=>"Lecca", "scopus_author_id"=>"35233959300"}, {"first_name"=>"Francesco", "last_name"=>"Marrosu", "scopus_author_id"=>"14048747500"}, {"first_name"=>"Maria Graziella", "last_name"=>"De Montis", "scopus_author_id"=>"7004644054"}, {"first_name"=>"Simona", "last_name"=>"Scheggi", "scopus_author_id"=>"6603202432"}, {"first_name"=>"Gianfranca", "last_name"=>"Carta", "scopus_author_id"=>"7101609523"}, {"first_name"=>"Elisabetta", "last_name"=>"Murru", "scopus_author_id"=>"6603655261"}, {"first_name"=>"Sonia", "last_name"=>"Aroni", "scopus_author_id"=>"55750130300"}, {"first_name"=>"Anna Lisa", "last_name"=>"Muntoni", "scopus_author_id"=>"35591621700"}, {"first_name"=>"Marco", "last_name"=>"Pistis", "scopus_author_id"=>"6701636492"}], "year"=>2013, "source"=>"PLoS ONE", "identifiers"=>{"sgr"=>"84878319533", "doi"=>"10.1371/journal.pone.0064541", "pui"=>"369013299", "pmid"=>"23724059", "scopus"=>"2-s2.0-84878319533", "issn"=>"19326203", "isbn"=>"1932-6203 (Electronic)\\n1932-6203 (Linking)"}, "id"=>"25d374da-f6dd-300d-8a10-ba7deada1fa8", "abstract"=>"Nicotinic acetylcholine receptors (nAChRs) are involved in seizure mechanisms. 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To this aim we utilized behavioral and electroencephalographic (EEG) experiments in C57BL/J6 mice and in vitro patch clamp recordings from mice and rats. Convulsive doses of nicotine evoked severe seizures and bursts of spike-waves discharges in ∼100% of mice. A single dose of the synthetic PPARα agonist WY14643 (WY, 80 mg/kg, i.p.) or chronic administration of fenofibrate, clinically available for lipid metabolism disorders, in the diet (0.2%) for 14 days significantly reduced or abolished behavioral and EEG expressions of nicotine-induced seizures. Acute WY effects were reverted by the PPARα antagonist MK886 (3 mg/kg, i.p.). Since neocortical networks are crucial in the generation of ictal activity and synchrony, we performed patch clamp recordings of spontaneous inhibitory postsynaptic currents (sIPSCs) from frontal cortex layer II/III pyramidal neurons. We found that both acute and chronic treatment with PPARα agonists abolished nicotine-induced sIPSC increases. PPARα within the CNS are key regulators of neuronal activity through modulation of nAChRs. These effects might be therapeutically exploited for idiopathic or genetically determined forms of epilepsy where nAChRs play a major role.", "link"=>"http://www.mendeley.com/research/pparalpha-agonists-novel-antiepileptic-drugs-preclinical-findings", "reader_count"=>30, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>4, "Researcher"=>9, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>5, "Other"=>5, "Student > Master"=>3, "Student > Bachelor"=>2}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>4, "Researcher"=>9, "Student > Doctoral Student"=>2, "Student > Ph. D. 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