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

Abstract

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).

Metabolic tinkering by the gut microbiome

“…37 Using a rat model, reduced neuronal spine density in pre-frontal cortex (PFC) neurons and hippocampal pyramidal neurons at postnatal day 35 (P35), which were then normalized by P70, was observed in Caesarean born animals compared with vaginally born controls. 99 Considering the likely differences in gut microbial colonization in this model, it will be interesting to elucidate whether these phenotypes are a consequence of differing microbial composition or colonization kinetics.…”

Obstetrical Mode of Delivery and Childhood Behavior and Psychological Development in a British Cohort

“…Birth by CS has been linked to psychological development through adulthood in animal models (Boksa and ElKhodor 2003;Juarez et al 2008). Some studies have linked birth by CS to an increased risk of autism spectrum disorders (ASD) (Hultman et al 2002), attention-deficit/hyperactivity disorder (ADHD) (Silva et al 2014) and behavioral difficulties (Kelmanson 2013) but results have been inconsistent (Burstyn et al 2010;Ketzer et al 2012).…”

Morphological Changes Induced by the Absence of Ovarian Hormones in Nucleus Accumbens of Ovariectomized Rats

“…(1). The neuronal dendritic morphology of NAcc neurons was measured by Golgi-Cox stain and dendritic length for each branching order, spine density and total dendritic length were obtained as reported previously [22,24,[28][29][30]. The GolgiCox impregnation procedure clearly filled the dendritic shafts and the spines of neurons from Nacc (Fig.…”

“…After rinsing, the sections were then immersed in the dark in Kodak Film Fixer for 30 min and subsequently washed with distilled water, dehydrated and cleared in successive baths of 50% (1 min), 70% (1 min), 95% (1 min) and 100% (2x5 min) alcohol followed by 15 min in a xylene solution. The slides were covered with balsam resinous medium [23,24].…”