Table 1.

Kynurenine pathway manipulation during development: Short and long-term effects.

Manipulation Model	Age of manipulation	KP alteration after manipulation	Age of testing	KP biochemistry at testing	Behavioral impairment	Structural/Functional changes in the brain	References
Embryonic Kynurenine (EKyn): Food laced with kynurenine fed to pregnant rat dams	ED 15 to ED 22	Increased fetal brain KYNA	PND 56	Increased KYNA in adult offspring	Impaired spatial learning, reference memory, and contextual memory		Pocivavsek et al., 2014
					Impaired attentional set-shifting	Decreased dendritic spine density, expression of α7nACh and mGluR2, and evoked glutamate release	Pershing et al., 2015
Pharmacological inhibition of KMO by treating pregnant rat dams with Ro-61-8048	ED 14, ED 16, and ED 18	Increased KYNA in the fetal brain	PND 21			Increased neuronal excitability, GluN2A/2B subunits, and PSD95	Forrest et al., 2013a
			PND 60			Decreased GluN2A and sonic hedgehog. Increased doublecortin. Paired-pulse stimulation deficit and impaired LTP	Forrest et al., 2013b
						Decreased dendritic spine number and complexity in hippocampus	Khalil et al., 2014
						Changes in various proteins including DISC1 and unc5H3 in the cerebellum, increased complexity of dendritic trees	Pisar et al., 2014
						Impaired LTP in hippocampus	Forrest et al., 2015
Developmental Kynurenine (DevKyn): Food laced with kynurenine fed to pregnant rat dams	ED15 to PND 21	Increased KYNA and 3-HK at weaning	PND 56	Increased KYNA, but no change in 3-HK, in adult offspring	Impaired spatial learning, reference memory, and contextual memory	Decreased extracellular glutamate in hippocampus	Pocivavsek et al., 2012
					Impaired attentional set-shifting	Decreased extracellular glutamate in prefrontal cortex	Alexander et al., 2013
Peripheral administration of kynurenine to rats	PND 7 to 10	Increased cortical KYNA and QUIN	PND 70		Impaired social behavior		Iaccarino et al., 2013
Peripheral administration of kynurenine to mice	PND 7 to 16	Increased cortical KYNA	PND 90		Impaired amphetamine-induced locomotor activity, pre-pulse inhibition, working memory in a trace-fear conditioning task	Potentiated dopamine release in response to d-amphetamine administration	Liu et al., 2014
Peripheral administration of kynurenines to rats	PND 27 to 35	Increased cortical KYNA	PND 61	No change in cortical KYNA in adult offspring	Impaired social behavior		Trecartin and Bucci, 2011
					Impaired novel object recognition and contextual fear memory		Akagbosu et al., 2012
					Increased motivational value by sign tracking	Impaired LTP	DeAngeli et al., 2014