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

Rubén Antonio Vázquez-Roque, Brenda Ramos, Carolina Tecuatl, Ismael Juárez, Anthony Adame, Fidel de la Cruz, Sergio Zamudio, Raúl Mena, Edward Rockenstein, Eliezer Masliah, Gonzalo Flores

Research output: Contribution to journalArticlepeer-review

54 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)288-306
Number of pages19
JournalJournal of Neuroscience Research
Volume90
Issue number1
DOIs
StatePublished - Jan 2012

Keywords

  • Cerebrolysin
  • Golgi-Cox stain
  • Neonatal ventral hippocampal lesion
  • Nucleus accumbens
  • Prefrontal cortex
  • Schizophrenia
  • Stereology

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