Pre-limbic cortex morphological alterations in an animal model of schizophrenia

The rat neonatal ventral hippocampal lesion (NVHL) has been proposed as a neurodevelopmental animal model of schizophrenia. In the present study, several morphometric analyses have been carried out in order to ascertain the presence of possible morphological alterations in the pre-limbic cortex of NVHL rats after puberty. Fractionator stereological analyses indicated that pre-limbic cortex volume is reduced in this animal model, without a significant reduction of the total number of NeuN-labeled neurons. NVHL also affected the morphological features of Golgi-Cox stained pyramidal neurons in this brain area. Furthermore, ultra-microscopy analyses highlighted that the density of asymmetric synapses is reduced in the pre-limbic cortex of lesioned rats when compared with shams. The results confirmed previous clinical brain imaging data indicating that a shrinkage of pre-frontal cortex may occur in schizophrenia, providing further support to the hypothesis that an early morphological insult may affect the correct development of pre-frontal cortex cyto-architecture. The reduced density of asymmetric synapses is in agreement with a possible impairment of pre-frontal cortex excitatory input in schizophrenia. To this regard, FIB-SEM 3D-reconstructions are in progress to evaluate possible alterations of synaptic contacts and volumes.