Ontogeny of altered dendritic morphology in the rat prefrontal cortex, hippocampus, and nucleus accumbens following Cesarean delivery and birth anoxia.

We used a delayed Cesarean birth model and the Golgi-Cox staining method to investigate the effects of perinatal anoxia on prefrontal cortex (PFC) and hippocampal (CA1) pyramidal neurons as well as nucleus accumbens (NAcc) medium spiny neurons. Dendritic morphology in these regions was studied on postnatal days (P) 2, 7, 14, 21, 35, and 70 in male Sprague-Dawley rats born either vaginally (VAG) or by Cesarean section either with (C + anoxia) or without (C-only) anoxia. The most striking birth group differences seen were at the level of dendritic spine densities on P35. During this postnatal period the dendritic spine density of PFC neurons was significantly lower in C + anoxia and C-only animals than in VAG controls; however, by P70 PFC spine densities in all birth groups were comparable. In contrast, hippocampal spine densities on P35 were comparably greater in C + anoxia animals than in VAG controls, whereas in C-only animals spine densities were lower than controls; here again, by P70 all groups had comparable hippocampal spine densities. In NAcc greater spine densities were seen on medium spiny neurons of C + anoxia animals on P35. These findings provide evidence that perinatal insult in the form of Cesarean birth with or without anoxia alters the dendritic development of PFC and hippocampal pyramidal neurons and to some extent also of NAcc medium spiny neurons. They also suggest that perinatal anoxia can alter the neuronal development of key structures thought to be affected in such late-onset dopamine-related disorders as schizophrenia and Attention Deficit Hyperactivity Disorder (ADHD). (c) 2008 Wiley-Liss, Inc.