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Metabolic Brain Disease

, Volume 30, Issue 4, pp 1043–1053 | Cite as

Maternal deprivation disrupts mitochondrial energy homeostasis in the brain of rats subjected to ketamine-induced schizophrenia

  • Alexandra Ioppi Zugno
  • Felipe Damázio Pacheco
  • Josiane Budni
  • Mariana Bittencourt de Oliveira
  • Lara Canever
  • Alexandra Stephanie Heylmann
  • Patrícia Gomes Wessler
  • Flávia da Rosa Silveira
  • Gustavo Antunes Mastella
  • Cinara Ludwig Gonçalves
  • Karoline V. Freitas
  • Adalberto Alves de Castro
  • Emilio L. Streck
  • João Quevedo
Research Article

Abstract

Maternal deprivation (MD) appears to be one of the environmental factors involved in the pathophysiology of schizophrenia. A widely used animal model of the schizophrenia involves the administration of ketamine, a dissociative anesthetic, NMDA receptors noncompetitive antagonist, that induce symptoms such as schizophrenia. To clarify the molecular mechanism of schizophrenia induced by MD, we investigated alterations in energetic metabolism, oxidative stress and neurotrophic factor levels in the brain of rats following MD and/or a single administration of ketamine during adulthood. Male Wistar rats were subjected to MD for 10 days. Additionally, these animals received acute ketamine (5, 15 or 25 mg/kg by intraperitoneal route, i.p.) during adulthood, and 30 min later, they were killed and the prefrontal cortex (PFC), the hippocampus and the striatum were removed for molecular analyses. Ketamine 25 mg/kg and/or MD and Ketamine 15 and 5 mg/kg with MD decreased the creatine kinase (CK) activity in the hippocampus. The enzyme activity of succinate dehydrogenase (SDH) in the Krebs cycle had increased in the striatum following the administration of ketamine 25 mg/kg, MD per se or MD plus ketamine 5 and 15 mg/kg. MD per se or MD combined with ketamine in different doses increased the activity of mitochondrial complexes. The PFC of animals subjected to MD and administered with ketamine 5 mg/kg exhibited increased protein carbonyl content. In the hippocampus, ketamine 15 mg/kg, ketamine 25 mg/kg and MD each increased the carbonyl content. In the striatum, the TBARS levels were increased by the administration of ketamine 25 mg/kg. Finally, in the hippocampus, MD alone or in combination with ketamine reduced the Nerve Growth Factor (NGF) levels; however, the Brain-derived Neurotrophic Factor (BDNF) levels were unaltered. In the present study, we suggest that MD increased the risk of psychotic symptoms in adulthood, altering different parameters of energy and oxidative stress. Our results suggest that adverse experiences occurring early in life may sensitize specific neurocircuits to subsequent stressors, inducing vulnerability, and may help us understand the pathophysiological mechanisms involved in this disorder.

Keywords

Schizophrenia Maternal deprivation Mitochondrial respiratory chain Krebs cycle Creatine kinase Oxidative stress 

Notes

Acknowledgments

Laboratory of Neurosciences (Brazil) is one of the centers of the National Institute for Translational Medicine (INCT-TM) and one of the members of the Center of Excellence in Applied Neurosciences of Santa Catarina (NENASC). This research was supported by grants from CNPq, Instituto Cérebro e Mente and UNESC (JQ and AIZ). JQ, ELS and AIZ are CNPq fellows.

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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Alexandra Ioppi Zugno
    • 1
  • Felipe Damázio Pacheco
    • 1
  • Josiane Budni
    • 1
  • Mariana Bittencourt de Oliveira
    • 1
  • Lara Canever
    • 1
  • Alexandra Stephanie Heylmann
    • 1
  • Patrícia Gomes Wessler
    • 1
  • Flávia da Rosa Silveira
    • 1
  • Gustavo Antunes Mastella
    • 1
  • Cinara Ludwig Gonçalves
    • 3
  • Karoline V. Freitas
    • 3
  • Adalberto Alves de Castro
    • 1
  • Emilio L. Streck
    • 3
  • João Quevedo
    • 1
    • 2
  1. 1.Laboratório de Neurociências, Programa de Pós-Graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da SaúdeUniversidade do Extremo Sul CatarinenseCriciúmaBrazil
  2. 2.Center for Experimental Models in Psychiatry, Department of Psychiatry and Behavioral SciencesThe University of Texas Medical School at HoustonHoustonUSA
  3. 3.Laboratório de Bioenergética, Programa de Pós-Graduação em Ciências da Saúde,Unidade Acadêmica de Ciências da SaúdeUniversidade do Extremo Sul CatarinenseCriciúmaBrazil

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