title: Early postnatal exposure to lithium in vitro induces changes in AMPAR mEPSCs and vesicular recycling at hippocampal glutamatergic synapses.
abstract: Lithium is an effective mood stabilizer but its use is associated with many side effects. Electrophysiological recordings of miniature excitatory postsynaptic currents (mEPSCs) mediated by glutamate receptor AMPA-subtype (AMPARs) in hippocampal pyramidal neurons revealed that CLi (therapeutic concentration of 1 mM lithium, from days in vitro 4-10) decreased the mean amplitude and mean rectification index (RI) of AMPAR mEPSCs. Lowered mean RI indicate that contribution of Ca2+ -permeable AMPARs in synaptic events is higher in CLi neurons (supported by experiments sensitive to Ca2+ -permeable AMPAR modulation). Co-inhibiting PKA, GSK-3 beta and glutamate reuptake was necessary to bring about changes in AMPAR mEPSCs similar to that seen in CLi neurons. FM1-43 experiments revealed that recycling pool size was affected in CLi cultures. Results from minimum loading, chlorpromazine treatment and hyperosmotic treatment experiments indicate that endocytosis in CLi is affected while not much difference is seen in modes of exocytosis. CLi cultures did not show the high KCl associated presynaptic potentiation observed in control cultures. This study, by calling attention to long-term lithium-exposure-induced synaptic changes, might have implications in understanding the side effects such as CNS complications occurring in perinatally exposed babies and cognitive dulling seen in patients on lithium treatment.
authors.affiliation: Molecular Biophysics Unit, Indian Institute of Science, Bangalore 560 012, India.
authors.forename: Shreya M
authors.initials: SM
authors.lastname: Ankolekar
authors.forename: Sujit K
authors.initials: SK
authors.lastname: Sikdar
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002746:Chlorpromazine / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D004705:Endocytosis / Q000502:physiology; D004781:Environmental Exposure / Q000009:adverse effects; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects*; D018698:Glutamic Acid / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors; D000071679:Glycogen Synthase Kinase 3 beta; D006624:Hippocampus / Q000166:cytology; D047908:Intracellular Signaling Peptides and Proteins / Q000494:pharmacology; D008094:Lithium / Q000494:pharmacology / Q000633:toxicity*; D055369:Miniature Postsynaptic Potentials / Q000187:drug effects*; D011726:Pyridinium Compounds / Q000494:pharmacology; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017470:Receptors, Glutamate / Q000187:drug effects*; D013569:Synapses / Q000378:metabolism*
chemical_list: C073804:FM1 43; D047908:Intracellular Signaling Peptides and Proteins; D011726:Pyridinium Compounds; D000644:Quaternary Ammonium Compounds; D017470:Receptors, Glutamate; C015482:protein kinase modulator; D018698:Glutamic Acid; D008094:Lithium; D000071679:Glycogen Synthase Kinase 3 beta; D017868:Cyclic AMP-Dependent Protein Kinases; D038362:Glycogen Synthase Kinase 3; D002746:Chlorpromazine