Early development of the brain's neural circuitry has been shown to be vulnerable to high levels of circulating steroid hormones such as corticosterone. These steroid hormones are lipophylic and can cross the placental barrier especially during the last week of gestation leading to disturbances in the formation of neural circuits that contain amongst others dopaminergic and serotonergic neurons. The effects of this disruption of neuronal circuit formation during gestation has been shown to manifest in adult offspring as behavioural abnormalities such as anxiety and an abnormal hypothalamic-pituitary-adrenal (HPA) axis. Models of prenatal stress include food deprivation and a model that involves exposure of the pregnant rats to different stressors, commonly referred to as a mild stress model. The objective of this study was to create a mild stress model that did not manifest as anxiety in adult offspring. In the last week of gestation, the pregnant dams were divided into three groups; (1) non-stressed (2) 50% food-deprived and (3) mildly stressed rats that we will refer to as the mildly stressed rats. Following birth, all pups were cross-fostered onto non-stressed dams and on postnatal day 60 (P60), behaviour in the elevated plus maze and the open field box was tested. On P66 the rats were exposed to an acute restraint stress following which trunk blood was collected for HPA axis analysis. The adrenal glands were also dissected and weighed. Results show that the mildly stressed rat model of prenatal stress is even milder than models described in the literature, since we did not find differences in time spent in the open arms of the elevated plus maze or adrenal gland size. In the open field, our model displayed slightly less locomotor activity and also had a slightly blunted adrenocorticotropic hormone (ACTH) response to restraint stress even though the corticosterone response was similar to controls.

The myelin-associated protein Nogo-A contributes to the failure of axon regeneration in the mammalian central nervous system (CNS). Inhibition of axon growth by Nogo-A is mediated by the Nogo-66 receptor (NgR). Nonmammalian vertebrates, however, are capable of spontaneous CNS axon regeneration, and we have shown that retinal ganglion cell (RGC) axons regenerate in the lizard Gallotia galloti. Using immunohistochemistry, we observed spatiotemporal regulation of Nogo-A and NgR in cell bodies and axons of RGCs during ontogeny. In the adult lizard, expression of Nogo-A was associated with myelinated axon tracts and upregulated in oligodendrocytes during RGC axon regeneration. NgR became upregulated in RGCs following optic nerve injury. In in vitro studies, Nogo-A-Fc failed to inhibit growth of lizard RGC axons. The inhibitor of protein kinase A (pkA) activity KT5720 blocked growth of lizard RGC axons on substrates of Nogo-A-Fc, but not laminin. On patterned substrates of Nogo-A-Fc, KT5720 caused restriction of axon growth to areas devoid of Nogo-A-Fc. Levels of cyclic adenosine monophosphate (cAMP) were elevated over sustained periods in lizard RGCs following optic nerve lesion. We conclude that Nogo-A and NgR are expressed in a mammalian-like pattern and are upregulated following optic nerve injury, but the presence of Nogo-A does not inhibit RGC axon regeneration in the lizard visual pathway. The results of outgrowth assays suggest that outgrowth-promoting substrates and activation of the cAMP/pkA signaling pathway play a key role in spontaneous lizard retinal axon regeneration in the presence of Nogo-A. Restriction of axon growth by patterned Nogo-A-Fc substrates suggests that Nogo-A may contribute to axon guidance in the lizard visual system. J. Comp. Neurol. 525:936-954, 2017. © 2016 Wiley Periodicals, Inc.