Kayla E. Rohr , Himanshu K. Mishra , Johansen Amin , Timothy Nakhla , Michael J. McCarthy
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引用次数: 0
Abstract
Bipolar disorder (BD) is a severe mental illness characterized by recurrent episodes of depression and mania. Lithium is the gold standard pharmacotherapy for BD, but outcomes are variable, and the relevant therapeutic mechanisms underlying successful treatment response remain uncertain. To identify synaptic markers of BD and lithium response, we measured the effects of lithium on induced pluripotent stem cell-derived neurons from BD patients and controls. We determined that baseline expression of synapsin I (SYN1) and PSD-95 is reduced in BD neurons compared to controls. In control neurons, lithium treatment had modest, transient effects increasing SYN1 and PSD-95 expression. In BD neurons, lithium increased SYN1 expression regardless of lithium response history. However, lithium only increased PSD-95 expression selectively in neurons from lithium-responders and not in neurons from lithium non-responders, leading to group differences in the colocalization of SYN1 and PSD-95. In conclusion, this preliminary work indicates synaptic protein markers are associated with BD pathology and correction of post-synaptic protein expression may be an important mechanism underlying lithium response.
期刊介绍:
Neuropharmacology publishes high quality, original research and review articles within the discipline of neuroscience, especially articles with a neuropharmacological component. However, papers within any area of neuroscience will be considered. The journal does not usually accept clinical research, although preclinical neuropharmacological studies in humans may be considered. The journal only considers submissions in which the chemical structures and compositions of experimental agents are readily available in the literature or disclosed by the authors in the submitted manuscript. Only in exceptional circumstances will natural products be considered, and then only if the preparation is well defined by scientific means. Neuropharmacology publishes articles of any length (original research and reviews).