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Chronic administration of the neurotrophic agent cerebrolysin ameliorates the behavioral and morphological changes induced by neonatal ventral hippocampus lesion in a rat model of schizophrenia
Author(s) -
VázquezRoque Rubén Antonio,
Ramos Brenda,
Tecuatl Carolina,
Juárez Ismael,
Adame Anthony,
de la Cruz Fidel,
Zamudio Sergio,
Mena Raúl,
Rockenstein Edward,
Masliah Eliezer,
Flores Gonzalo
Publication year - 2012
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.22753
Subject(s) - dendritic spine , prepulse inhibition , nucleus accumbens , neuroscience , lesion , hippocampal formation , hippocampus , prefrontal cortex , psychology , ventral tegmental area , neurotrophic factors , amphetamine , schizophrenia (object oriented programming) , medicine , central nervous system , dopamine , cognition , psychiatry , receptor , dopaminergic
Neonatal ventral hippocampal lesion (nVHL) in rats has been widely used as a neurodevelopmental model to mimic schizophrenia‐like behaviors. Recently, we reported that nVHLs result in dendritic retraction and spine loss in prefrontal cortex (PFC) pyramidal neurons and medium spiny neurons of the nucleus accumbens (NAcc). Cerebrolysin (Cbl), a neurotrophic peptide mixture, has been reported to ameliorate the synaptic and dendritic pathology in models of aging and neurodevelopmental disorder such as Rett syndrome. This study sought to determine whether Cbl was capable of reducing behavioral and neuronal alterations in nVHL rats. The behavioral analysis included locomotor activity induced by novel environment and amphetamine, social interaction, and sensoriomotor gating. The morphological evaluation included dendritic analysis by using the Golgi‐Cox procedure and stereology to quantify the total cell number in PFC and NAcc. Behavioral data show a reduction in the hyperresponsiveness to novel environment‐ and amphetamine‐induced locomotion, with an increase in the total time spent in social interactions and in prepulse inhibition in Cbl‐treated nVHL rats. In addition, neuropathological analysis of the limbic regions also showed amelioration of dendritic retraction and spine loss in Cbl‐treated nVHL rats. Cbl treatment also ameliorated dendritic pathology and neuronal loss in the PFC and NAcc in nVHL rats. This study demonstrates that Cbl promotes behavioral improvements and recovery of dendritic neuronal damage in postpubertal nVHL rats and suggests that Cbl may have neurotrophic effects in this neurodevelopmental model of schizophrenia. These findings support the possibility that Cbl has beneficial effects in the management of schizophrenia symptoms. © 2011 Wiley Periodicals, Inc.