Poster Presentation & Flash Talk 46th Annual Meeting of the Fetal and Neonatal Physiological Society 2019

Cortical development following intrauterine growth restriction in the neonatal and adolescent rat (#140)

Angela Cumberland 1 , Abiramy Selvanathan 1 , Courtney Gilchrist 1 , Aminath Azhan 2 , Delphi Kondos-Devcic 1 , Madhavi Khore 1 , Mary Tolcos 1
  1. Neurodevelopment in Health & Disease Program, RMIT University, Bundoora, Victoria, Australia
  2. Hudson Institute of Medical Research, Clayton, Victoria, Australia

Background: Intrauterine growth restriction (IUGR) is associated with impaired neurodevelopment and cognition. The neocortex develops in a highly structured manner, and disturbances to its formation have implications in many neuropsychiatric disorders. However, whether IUGR interferes with cortical development is unknown. This study aimed to determine if cortical development is impaired following IUGR.

 

Methods: At day 18 of pregnancy (term=22 days), rats underwent bilateral uterine vessel ligation (n=11) or sham surgery (n=9) to generate IUGR and control pups. Brains were collected and weighed at either postnatal (P) 7 (control n=4; IUGR n=6) or P45 (control n=10; IUGR n=11). Immunostaining for Ctip2 (layer V-VI; corticospinal projection neurons) and Satb2 (layer II-VI; corticocallosal projection neurons) was assessed in motor (MOT), somatosensory (SOM) and auditory (AUD) cortices at the level of the dorsal hippocampus. Data was analysed by a two-way ANOVA with Bonferroni post-hoc testing.

 

Results: At P7, IUGR rats weighed less than controls (p=0.024) but had normalised to controls at P45. Brain weight and cortical thickness was not different between IUGR and control rats at both ages. At P7 there was an increase in Satb2+ve (SOM: p=0.0013; AUD: p=0.0043) and Ctip2+ve (SOM: p=0.0008; AUD: p=0.0004) cell density in IUGR compared to control pups; there was no difference in the MOT. At P45, there was a reduction in the density of Satb2+ve cells in the cerebral cortex overall (p=0.04) in IUGR compared to control rats, but this was not specific to any region; there were no differences in Ctip2+ve cells between groups.

 

Conclusion: Corticospinal and corticocallosal projection neurons are increased in the cerebral cortex of the IUGR neonate but are somewhat restored (or reduced) in adolescents. Despite this, changes in projection neuron populations during brain development could influence connectivity and possibly lead to cortical dysfunction. Other neuronal populations and neurobehaviour need to be assessed.