title: Neurotoxicity and reactive astrogliosis in the anterior cingulate cortex in acute ciguatera poisoning.
abstract: Ciguatoxins (CTXs) cause long-term disturbance of cerebral functions. The primary mechanism of neurotoxicity is related to their interaction with voltage-gated sodium channels. However, until now, the neurological targets for CTXs in the brain of intact animals have not been described. In our study, 1 day following oral exposure to 0.26 ng/g of Pacific ciguatoxin 1 (P-CTX-1), we performed in vivo electrophysiological recordings in the rat anterior cingulate cortex (ACC) and identified the increase in spontaneous firings and enhanced responses to visceral noxious stimulation. Local field recordings characterized the P-CTX-1-induced synaptic potentiation and blockage of the induction of electrical stimulation-induced long-term potentiation in the medial thalamus (MT)-ACC pathway. Furthermore, intracerebroventricular administration of P-CTX-1 at doses of 1.0, 5.0, and 10 nM produced a dose-dependent increase in ACC neuronal firings and MT-ACC synaptic transmission. Further studies showed upregulated Na(+) channel expression in astrocytes under pathological conditions. We hypothesized that the astrocytes might have been activated in the ciguatera poisoning in vivo. Increases in glial fibrillary acid protein expression were detected in reactive astrocytes in the rat ACC. The activation of astroglia was further indicated by activation of the gap junction protein connexin 43 and upregulation of excitatory amino acid transporter 2 expression suggesting that glutamate was normally rapidly cleared from the synaptic cleft during acute ciguatera poisoning. However, neurotoxicity and reactive astrogliosis were not detected in the ACC after 7 days of P-CTX-1 exposure. The present results are the first characterization of P-CTX-1-invoked brain cortex neuronal excitotoxicity in vivo and supported the theme that neuron and astroglia signals might play roles in acute ciguatera poisoning.
authors.affiliation: Neuroscience Laboratory, Department of Biology and Chemistry, City University of Hong Kong, Tat Chee Avenue, Kowloon, Hong Kong, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Zhang
authors.forename: Bing
authors.initials: B
authors.lastname: Cao
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Jin
authors.initials: J
authors.lastname: Liu
authors.forename: Vivian Oi Vian
authors.initials: VO
authors.lastname: Tung
authors.forename: Paul Kwan Sing
authors.initials: PK
authors.lastname: Lam
authors.forename: Leo Lai
authors.initials: LL
authors.lastname: Chan
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000284:Administration, Oral; D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000473:pathology; D001835:Body Weight / Q000187:drug effects; D036841:Ciguatera Poisoning / Q000473:pathology* / Q000503:physiopathology; D002922:Ciguatoxins / Q000008:administration & dosage / Q000633:toxicity*; D018031:Connexin 43 / Q000378:metabolism; D003289:Convalescence; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D027342:Excitatory Amino Acid Transporter 2 / Q000378:metabolism; D005911:Gliosis / Q000209:etiology* / Q000473:pathology; D006179:Gyrus Cinguli / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D017774:Long-Term Potentiation / Q000187:drug effects; D008297:Male; D017551:Microdialysis; D009474:Neurons / Q000187:drug effects; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D009435:Synaptic Transmission / Q000187:drug effects*; D013788:Thalamus / Q000187:drug effects / Q000503:physiopathology; D061566:Voltage-Gated Sodium Channels / Q000187:drug effects
chemical_list: D018031:Connexin 43; D018691:Excitatory Amino Acid Antagonists; D027342:Excitatory Amino Acid Transporter 2; C580592:Gja1 protein, rat; C493395:Slc1a2 protein, rat; D061566:Voltage-Gated Sodium Channels; D002922:Ciguatoxins