title: Lithium increases hippocampal SNARE protein abundance after traumatic brain injury.
abstract: Rodent models of traumatic brain injury (TBI) reproduce secondary injury sequela and cognitive impairments observed in patients afflicted by a TBI. Impaired neurotransmission has been reported in the weeks following experimental TBI, and may be a contributor to behavioral dysfunction. The soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex, the machinery facilitating vesicular docking and fusion, is a highly-conserved mechanism important for neurotransmission. Following TBI, there is a reduction in both the formation of the SNARE complex and the abundance of multiple SNARE proteins, including the chaperone protein cysteine string protein α (CSPα). Treatment with lithium in naïve rats reportedly increases the expression of CSPα. In the context of TBI, brain-injured rats treated with lithium exhibit improved outcome in published reports, but the mechanisms underlying the improvement are poorly understood. The current study evaluated the effect of lithium administration on the abundance of SNARE proteins and SNARE complex formation, hemispheric tissue loss, and neurobehavioral performance following controlled cortical impact (CCI). Sprague Dawley rats were subjected to CCI or sham injury, and treated daily with lithium chloride or vehicle for up to 14days. Administration of lithium after TBI modestly improved spatial memory at 14days post-injury. Semi-quantitative immunoblot analysis of hippocampal lysates revealed that treatment with lithium attenuated reductions in key SNARE proteins and SNARE complex formation at multiple time points post-injury. These findings highlight that treatment with lithium increased the abundance of synaptic proteins that facilitate neurotransmission and may contribute to improved cognitive function after TBI.
authors.affiliation: Department of Neurosurgery, Safar Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, PA, United States; V.A. Pittsburgh Healthcare System, Pittsburgh, PA, United States.
authors.forename: Shaun W
authors.initials: SW
authors.lastname: Carlson
authors.affiliation: Department of Neurosurgery, Safar Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, PA, United States; V.A. Pittsburgh Healthcare System, Pittsburgh, PA, United States.
authors.forename: Hong
authors.initials: H
authors.lastname: Yan
authors.affiliation: Department of Neurosurgery, Safar Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, PA, United States; V.A. Pittsburgh Healthcare System, Pittsburgh, PA, United States. Electronic address: dixoec@upmc.edu.
authors.forename: C Edward
authors.initials: CE
authors.lastname: Dixon
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D018692:Antimanic Agents / Q000494:pharmacology*; D000070642:Brain Injuries, Traumatic / Q000150:complications / Q000473:pathology*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D007859:Learning Disabilities / Q000188:drug therapy / Q000209:etiology; D018021:Lithium Chloride / Q000494:pharmacology*; D008297:Male; D011596:Psychomotor Disorders / Q000188:drug therapy / Q000209:etiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D050600:SNARE Proteins / Q000378:metabolism*; D065853:Spatial Learning / Q000187:drug effects; D016708:Synaptophysin / Q000378:metabolism; D050825:Synaptosomal-Associated Protein 25 / Q000378:metabolism; D013997:Time Factors; D050988:Vesicle-Associated Membrane Protein 2 / Q000378:metabolism; D051844:alpha-Synuclein / Q000378:metabolism
chemical_list: D018692:Antimanic Agents; D050600:SNARE Proteins; C494210:Snap25 protein, rat; D016708:Synaptophysin; D050825:Synaptosomal-Associated Protein 25; D050988:Vesicle-Associated Membrane Protein 2; D051844:alpha-Synuclein; D018021:Lithium Chloride
keywords: Cognition; Hippocampus; SNARE; Synapse; Traumatic brain injury; Vesicle