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J Neurotrauma. 2018 Dec 1;35(23):2827-2836. doi: 10.1089/neu.2017.5509. Epub 2018 Aug 13.

Lithium Improves Dopamine Neurotransmission and Increases Dopaminergic Protein Abundance in the Striatum after Traumatic Brain Injury.

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Department of Neurological Surgery, Safar Center for Resuscitation Research, VA Pittsburgh Healthcare System, University of Pittsburgh , Pittsburgh, Pennsylvania.


Experimental models of traumatic brain injury (TBI) recapitulate secondary injury sequela and cognitive dysfunction reported in patients afflicted with a TBI. Impairments in neurotransmission are reported in multiple brain regions in the weeks following experimental TBI and may contribute to behavioral dysfunction. Formation of the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex is an important mechanism for neurotransmitter exocytosis. We previously showed that lithium treatment attenuated hippocampal decreases in α-synuclein and VAMP2, enhanced SNARE complex formation, and improved cognitive performance after TBI. However, the effect of TBI on striatal SNARE complex formation is not known. We hypothesized lithium treatment would attenuate TBI-induced impairments in evoked dopamine release and increase the abundance of synaptic proteins associated with dopamine neurotransmission. The current study evaluated the effect of lithium (1 mmol/kg/day) administration on striatal evoked dopamine neurotransmission, SNARE complex formation, and proposed actions of lithium, including inhibition of GSK3β, assessment of synaptic marker protein abundance, and synaptic proteins important for dopamine synthesis and transport following controlled cortical impact (CCI). Sprague-Dawley rats were subjected to CCI or sham injury and treated daily with lithium chloride or vehicle for 7 days post-injury. We provide novel evidence that CCI reduces SNARE protein and SNARE complex abundance in the striatum at 1 week post-injury. Lithium administration improved evoked dopamine release and increased the abundance of α-synuclein, D2 receptor, and phosphorylated tyrosine hydroxylase in striatal synaptosomes post-injury. These findings show that lithium treatment attenuated dopamine neurotransmission deficits and increased the abundance of synaptic proteins important for dopamine signaling after TBI.


SNARE; alpha synuclein; dopamine; neurotransmission; striatum; traumatic brain injury

[Available on 2019-12-01]

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