pr5009493_si_003.xlsx (60.06 kB)
A Targeted Multiplexed Proteomic Investigation Identifies Ketamine-Induced Changes in Immune Markers in Rat Serum and Expression Changes in Protein Kinases/Phosphatases in Rat Brain
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posted on 2015-01-02, 00:00 authored by Hendrik Wesseling, Hassan Rahmoune, Mark Tricklebank, Paul C. Guest, Sabine BahnThere
is substantial interest in the N-methyl-d-aspartate (NMDA) receptor antagonist ketamine in psychiatric
research because it exerts acute psychotomimetic and rapid antidepressant
effects in rodents and humans. Here, we investigated proteomic changes
in brain and serum after acute treatment of rats with ketamine using
two targeted proteomic profiling methods. Multiplex immunoassay profiling
of serum identified altered levels of interleukin 4, tumor necrosis
factor alpha, and fibroblast growth factor 9, suggesting a link between
ketamine exposure and peripheral inflammation and growth factor dysregulation.
Selected reaction monitoring mass spectrometry profiling of rat brain
tissue found that proteomic changes occurred in the frontal cortex
and to a greater extent in the hippocampus. This involved changes
in signaling kinases and proteases such as protein kinase C beta,
neurochondrin (NCDN), calcineurin, extracellular signal-regulated
kinsase 1 (ERK1), and mammalian target of rapamycin (MTOR). Furthermore,
altered levels were found for proteins associated with neurotransmitter
metabolism (mitochondrial aspartate aminotransferase, catechol O-methyl transferase, synaptic vesicle endo-/exocytosis
(vesicle fusing ATPase (NSF), synapsin 1 (SYN1), syndapin-1 (PACN1)).
Consistent with previous global proteomic studies, we confirmed known
changes in mitochondrial complex I, prohibitin (PHB) and neurofilament
proteins (neurofilament light chain and α-internexin (AINX)).
Taken together, the proteomic changes parallel those described in
human psychiatric pathology. The results will help to elucidate ketamine’s
mechanism of action, which will facilitate development of novel drugs
for the treatment of schizophrenia and major depressive disorder.