Early postnatal exposure to lithium in vitro induces changes in AMPAR mEPSCs and vesicular recycling at hippocampal glutamatergic synapses.
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Date
2015-06
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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-3β 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.
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Keywords
AMPARs, FM1-43, hippocampal glutamatergic synapses, lithium side effects, mEPSCs, rectification index, synaptic recycling
Citation
Ankolekar Shreya M, Sikdar Sujit K. Early postnatal exposure to lithium in vitro induces changes in AMPAR mEPSCs and vesicular recycling at hippocampal glutamatergic synapses. Journal of Biosciences. 2015 June; 40(2): 339-354.