ABSTRACT
Redox-altered plasticity refers to redox-dependent reversible changes in synaptic plasticity
ABSTRACT
Previous studies demonstrate that diabetes mellitus induces cognitive impairment,leading to diabetic encephalopathy(DE), which is closely related with hippocampal synaptic plasticity impairment,including synaptic structural and functional damage. Structural damage mainly embodied in the synapse degeneration.Functional damage mainly reflects in the LTP damage, including the composition variation and functional lesions of N-methyl-D-aspartate receptors(NMDARs), α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs) and patassium channels.Abnormal synaptic plasticity may be critical in the pathogenesis of diabetic encephalopathy. In this review, we summarized the relationship between DE and synaptic plasticity impairment.
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.