Prenatal stress reduces interneuronal connectivity in the rat cerebellar granular layer

The development and functioning of the central nervous system have been shown to be affected by maternal stress. To investigate the effects of prenatal stress on the cerebellar interneuronal connectivity, rat embryos are exposed to stress on their embryonic day (E) 7 and 14, by keeping the dam in close-fitting wire mesh cylinders, for 6 h. After completion of the cerebellar development at postnatal day (P) 30, stereological procedures were used at the light and electron microscopic level to analyze growth parameters of the granule cells and synapse-to-neuron ratios. Neither the volume fraction (V(V)) of the granular layer to whole cortex, nor the numerical density of granule cells (N(Vg)) per unit volume of granular layer was affected by exposure to stress. However, the mean granule cell nuclear diameter was significantly decreased in stressed animals. Within the neuropil region, the number and mean diameter of synaptic disc profiles were used to estimate the numerical density of synapses (N(Vs)). Synapse-to-neuron ratio was obtained by dividing N(Vs) with N(Vg), and found significantly lower in the stressed group than the control group. In addition, synaptophysin immunoreactivity showed a significant decrease (41%) in the granular layer of the cerebellum. Collectively, these results demonstrate that intrauterine stress alters the morphology of granule cells and causes a profound and fairly long-lasting deficit in their interneuronal connectivity.