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Published in final edited form as: Nat Rev Neurosci. 2012 Jul;13(7):465–477. doi: 10.1038/nrn3257

A: Inhibition of endogenous KYNA synthesis with the KAT II inhibitor (S)-4-(ethylsulfonyl)benzoylalanine (ESBA), administered intracerebroventricularly 90 min prior to daily training (Days 1–4), facilitates learning in a spatial working memory task (the Morris water maze test) in normal rats. Co-administration of KYNA eliminates this effect (see ⁷² for details); B: JM6, a peripherally acting pro-drug of the KMO inhibitor Ro 61-8048, prevents synaptic loss in a transgenic mouse model of Alzheimer’s disease (APPtg mice). JM6 was administered orally for 120 days, and the brain was evaluated in 8-month-old APPtg mice. Left: Representative image (630X) of serial sections of the hippocampus of wild-type or APPtg mice immunostained with an antibody for synaptophysin. Right: Quantification of synaptophysin levels in the hippocampus of APPtg mice treated with JM6. Synaptophysin levels in APPtg mice treated with JM6 are not significantly different from those found in wild-type mice (see ¹⁷² for details).

A: Inhibition of endogenous KYNA synthesis with the KAT II inhibitor (S)-4-(ethylsulfonyl)benzoylalanine (ESBA), administered intracerebroventricularly 90 min prior to daily training (Days 1–4), facilitates learning in a spatial working memory task (the Morris water maze test) in normal rats. Co-administration of KYNA eliminates this effect (see ⁷² for details); B: JM6, a peripherally acting pro-drug of the KMO inhibitor Ro 61-8048, prevents synaptic loss in a transgenic mouse model of Alzheimer’s disease (APPtg mice). JM6 was administered orally for 120 days, and the brain was evaluated in 8-month-old APPtg mice. Left: Representative image (630X) of serial sections of the hippocampus of wild-type or APPtg mice immunostained with an antibody for synaptophysin. Right: Quantification of synaptophysin levels in the hippocampus of APPtg mice treated with JM6. Synaptophysin levels in APPtg mice treated with JM6 are not significantly different from those found in wild-type mice (see ¹⁷² for details).