title: 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.
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.
authors.affiliation: Laboratorio de Neuropsiquiatría, Instituto de Fisiología, Universidad Autónoma de Puebla, Puebla, México.
authors.forename: Rubén Antonio
authors.initials: RA
authors.lastname: Vázquez-Roque
authors.forename: Brenda
authors.initials: B
authors.lastname: Ramos
authors.forename: Carolina
authors.initials: C
authors.lastname: Tecuatl
authors.forename: Ismael
authors.initials: I
authors.lastname: Juárez
authors.forename: Anthony
authors.initials: A
authors.lastname: Adame
authors.forename: Fidel
authors.initials: F
authors.lastname: de la Cruz
authors.forename: Sergio
authors.initials: S
authors.lastname: Zamudio
authors.forename: Raúl
authors.initials: R
authors.lastname: Mena
authors.forename: Edward
authors.initials: E
authors.lastname: Rockenstein
authors.forename: Eliezer
authors.initials: E
authors.lastname: Masliah
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Flores
mesh_terms: D000161:Acoustic Stimulation; D000596:Amino Acids / Q000008:administration & dosage*; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal / Q000187:drug effects*; D049229:Dendritic Spines / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D004195:Disease Models, Animal; D005260:Female; D006624:Hippocampus / Q000293:injuries*; D007266:Inhibition, Psychological; D007398:Interpersonal Relations; D009043:Motor Activity / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013216:Reflex, Startle; D012559:Schizophrenia / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D016622:Silver Staining
chemical_list: D000596:Amino Acids; D018696:Neuroprotective Agents; C006952:cerebrolysin