title: Canadian boreal pulp and paper feedstocks contain neuroactive substances that interact in vitro with GABA and dopaminergic systems in the brain.
abstract: Pulp and paper wood feedstocks have been previously implicated as a source of chemicals with the ability to interact with or disrupt key neuroendocrine endpoints important in the control of reproduction. We tested nine Canadian conifers commonly used in pulp and paper production as well as 16 phytochemicals that have been observed in various pulp and paper mill effluent streams for their ability to interact in vitro with the enzymes monoamine oxidase (MAO), glutamic acid decarboxylase (GAD), and GABA-transaminase (GABA-T), and bind to the benzodiazepine-binding site of the GABA(A) receptor (GABA(A)-BZD). These neuroendocrine endpoints are also important targets for treatment of neurological disorders such as anxiety, epilepsy, or depression. MAO and GAD were inhibited by various conifer extracts of different polarities, including major feedstocks such as balsam fir, black spruce, and white spruce. MAO was selectively stimulated or inhibited by many of the tested phytochemicals, with inhibition observed by a group of phenylpropenes (e.g. isoeugenol and vanillin). Selective GAD inhibition was also observed, with all of the resin acids tested being inhibitory. GABA(A)-BZD ligand displacement was also observed. We compiled a table identifying which of these phytochemicals have been described in each of the species tested here. Given the diversity of conifer species and plant chemicals with these specific neuroactivities, it is reasonable to propose that MAO and GAD inhibition reported in effluents is phytochemical in origin. We propose disruption of these neuroendocrine endpoints as a possible mechanism of reproductive inhibition, and also identify an avenue for potential research and sourcing of conifer-derived neuroactive natural products.
authors.affiliation: Department of Biology, University of Ottawa, 30 Marie-Curie, Ottawa, Ontario K1N 6N5, Canada.
authors.forename: Andrew
authors.initials: A
authors.lastname: Waye
authors.forename: Malar
authors.initials: M
authors.lastname: Annal
authors.forename: Andrew
authors.initials: A
authors.lastname: Tang
authors.forename: Gabriel
authors.initials: G
authors.lastname: Picard
authors.forename: Frédéric
authors.initials: F
authors.lastname: Harnois
authors.forename: José A
authors.initials: JA
authors.lastname: Guerrero-Analco
authors.forename: Ammar
authors.initials: A
authors.lastname: Saleem
authors.forename: L Mark
authors.initials: LM
authors.lastname: Hewitt
authors.forename: Craig B
authors.initials: CB
authors.lastname: Milestone
authors.forename: Deborah L
authors.initials: DL
authors.lastname: MacLatchy
authors.forename: Vance L
authors.initials: VL
authors.lastname: Trudeau
authors.forename: John T
authors.initials: JT
authors.lastname: Arnason
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002170:Canada; D059290:Dopaminergic Neurons / Q000378:metabolism*; D005968:Glutamate Decarboxylase / Q000037:antagonists & inhibitors / Q000378:metabolism; D006054:Goldfish; D008995:Monoamine Oxidase / Q000378:metabolism; D009490:Neurosecretory Systems / Q000187:drug effects*; D010209:Paper; D010936:Plant Extracts / Q000494:pharmacology*; D051381:Rats; D012588:Scintillation Counting; D064028:Tracheophyta / Q000737:chemistry*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D010936:Plant Extracts; D005680:gamma-Aminobutyric Acid; D008995:Monoamine Oxidase; D005968:Glutamate Decarboxylase
keywords: DA; Dopamine; GABA; GABA(A) receptor benzodiazepine-binding site; GABA(A)-BZD; GABA-T; GABA-transaminase; GAD; Gamma-aminobutyric acid; GnRH; LH; MAO; Natural products; Neuroendocrine disruption; Phytochemistry; Pulp and paper conifer feedstocks; dopamine; gamma-aminobutyric acid; glutamic acid decarboxylase; gonadotropin-releasing hormone; luteinizing hormone; monoamine oxidase