The deficit of quinolinic acid phosphoribosyltransferase induces hypolocomotion and cognitive impairment through impairment of dopaminergic neuronal function

Quinolinic acid (QA) is a neurotoxic and implicated in the neurological disorders. QA is metabolized by quinolinic acid phosphoribosyltransferase (QPRT). However, the physiological roles of QPRT in central nervous system are still unclear. To investigate the roles of QPRT in emotional and cognitive functions, QPRT KO mice were subjected to several types of neurobehavioral tests. The KO mice decreased locomotor activity in novel environment, prolonged escape latency in Barns maze test, and decreased alternation behavior in Y-maze test. In the KO mice, the contents of homovanillic acid (HVA) and 3,4-Dihydroxyphenylacetic acid (DOPAC), and the ratios of HVA/ dopamine (DA) in the nucleus accumbens and DOPAC/DA in the prefrontal cortex were decrease. In the immunohistochemistry, the number of tyrosine hydroxylase (TH)-positive neuron was less compared with wild mice. Taken together, the present findings suggest a novel role of QPRT in hypolocomotion and cognitive impairment in relation to impairment of dopaminergic functions in the nucleus accumbens and prefrontal cortex, respectively.