Abstract Three million people worldwide are exposed to organophosphates (OP), most of whom will survive with long term side effects. These side effects include cognitive problems, mood disorders, and other neurological issues. These side effects have underlaying molecular mechanisms which have yet to be uncovered. This knowledge gap is a direct result of a lack of research tools available, however, two new tools have recently become available to close this knowledge gap. The first is a novel mouse model, termed the KIKO mouse, which contains two key genetic modifications: 1. knock out of the OP-binding serum carboxylesterase and 2. knock in of the human acetylcholine esterase. These modifications produce a vastly improved rodent model of OP intoxication. The other is matrix assisted laser desorption ionization (MALDI) mass spectrometry imaging (MSI). MALDI MSI combines the power of mass spectrometry with spatial resolution. Briefly, discrete mass spectrometry experiments are generated across a fresh-frozen tissue section to generate ion density maps of metabolites, neurotransmitters, lipids, and N-glycans. These two novel and powerful tools will allow for unprecedented molecular information on the short- and long-term effects of OP intoxication. We hypothesize that OP intoxication generates significant molecular changes in neurotransmitters, metabolites, lipids, and N-glycans. Our preliminary data shows significant differences in metabolites, neurotransmitters, and lipid oxidation in KIKO mice fifteen minutes post-exposure. Literature data supports changes in N-glycans associated with neuroinflammation. To test this hypothesis, in Aims 1 and 2, we will expose KIKO mice to 1xLD50 of sarin followed by the currently fielded countermeasure 2-PAM and atropine. Control animals will be given an equivalent volume of water for both exposure and treatment. Animals will be euthanized at 24 hours, 3-, 6-, and 12-weeks post exposure for analysis of metabolites, neurotransmitters, lipids, and N-glycans from brain, spinal cord, and blood. In Aim 3 we will expose pregnant KIKO mice to 1xLD50 of sarin followed by the currently fielded countermeasure. Dames will be allowed to continue their pregnancy and the offspring will be euthanized at early adult (8 weeks), mature adult (14 to 16 weeks), mid-life (40 weeks) and geriatric (78 weeks) of age for analysis by MALDI MSI. Brains, spines, and blood will be collected for analysis of metabolites, neurotransmitters, lipids, and N-glycans. From these data we will generate novel targets in the treatment of OP intoxication and its long term side effects.