Expression of kynurenine aminotransferase in the subplate of the rat and its possible role in the regulation of programmed cell death.

The neurons of the transient subplate zone, considered important for the prenatal development of the cerebral cortex, were shown here to express kynurenine aminotransferase (KAT)-I from embryonic day (E) 16 until postnatal day (P) 7 in the rat. No other cells of brain tissue exerted KAT-I immunoreactivity during this period. From P3 on, the neurons of the subplate gave rise to KAT-I immunoreactive, varicose axons, which entered the thalamus and terminated around thalamic nerve cells that are devoid of KAT-I immunoreactivity. Other subplate markers displayed a different expression pattern during development. Thus, subplate neurons displayed parvalbumin (PV) immuno-reactivity from E16 to P10 and an intense NPY immunoreaction from P7 to P1. They also exhibited nitric oxide synthase immunoreactivity from E16 to P10, whereas on the surface of the subplate neurons, the alpha7 subunit of the nicotinic acetylcholine receptor (nAChR) was present from P1 to P10. The cells of Cajal-Retzius were nAChR-immunoreactive during this period. Between P1 and P7, the perikarya of subplate neurons also showed an intense immuno-reaction with the N-methyl-D-aspartate (NMDA) receptor subtype R2A. After the first postnatal week, many of the KAT-I positive subplate neurons display a gradual decrease of immunoreactivity and undergo programmed cell death. Since KAT-I persists in the subplate through the period E16-P7, we conclude that KAT-I is a useful and reliable subplate marker in the rat. Since it is assumed that migration of nerve cells is regulated by NMDA receptors, and since kynurenic acid--the only naturally occurring NMDA receptor antagonist--is synthesized by KAT, we suggest that a temporary breakdown of the delicate equilibrium between NMDA and KAT might induce abnormal neuronal migration, giving rise to developmental abnormalities.