Perinatal Asphyxia Reduces the Number of Reelin Neurons in the Prelimbic Cortex and Deteriorates Social Interaction in Rats

PABLO VÁZQUEZ-BORSETTI, ELENA PEÑA, CATALINA RICO, MARIANA NOTO, NATHALIE MILLER, DIEGO COHON, JUAN MANUEL ACOSTA, MARIANO IBARRA; FABIÁN LOIDL

DEVELOPMENTAL NEUROSCIENCE

KARGER

Lugar: Basel; Año: 2016 vol. 38 p. 241 - 250

0378-5866

Obstetrical complications of perinatal asphyxia (PA) can ofteninduce lesions that, in the long-term, manifest as schizophrenia.A deterioration of the medial prefrontal cortex(mPFC) and a reduction in the number of GABAergic neuronsare commonly observed in the pathophysiology of schizophrenia.In this study, we investigated the link between PA,reelin and calbindin diminution and psychiatric diseasesthat involve social interaction deficits. This was achieved byobserving the effect of 19 min of asphyxia on both subpopulationsof GABAergic neurons. PA was produced by water immersionof fetus-containing uterus horns removed by cesareansection from ready-to-deliver rats. PA generated asignificant and specific decrease in the number ofreelin-secreting neurons in mPFC layer VI [F(2, 6) = 8.716,p = 0.016; PA vs. vaginal controls (VC), p = 0.03, and PA vs.cesarean controls (CC), p = 0.022]. This reduction reachedapproximately 60% on average. Changes in the percentageof reelin neurons including all the cortex layers did notachieve a significant outcome but a trend: CC % 10.61 ± 1.34; PA % 8.64 ± 1.71 [F(2, 6) = 1.299, p = 0.33]. In the case of calbindin,there was a significant decrease in cell density in thePA group [2-way repeated-measures ANOVA, F(1, 4) = 13.03,p = 0.0226]. The multiple-comparisons test showed significantdifferences in the superficial aspect of layer II (Sidak testfor multiple comparisons CC vs. PA at 200 μm: p = 0.003). Asmall, but significant difference could be seen when the distancefrom the pia mater to the start of layer VI was analyzed(CC mean ± SEM = 768.9 ± 8.382; PA mean ± SEM = 669.3 ±17.75; p = 0.036). Rats exposed to PA showed deteriorationin social interactions, which manifested as a decrease in playsoliciting. In this model, which involved severe/moderate asphyxia,we did not find significant changes in locomotive activityor anxiety indicators in the open field task. The loss ofreelin neurons could be conducive to the shrinkage of theprelimbic cortex through the reduction in neuropil and thedeterioration of the function of this structure.