Abstract
Neonatal blockade of N-methyl-D-aspartic acid (NMDA) receptors represents one of experimental animal models for schizophrenia. This study is to investigate the long-term brain-derived neurotrophic factor (BDNF) expression profiles in different regions and correlation with “schizophrenia-like” behaviors in the adolescence and adult of this rat model. The NMDA receptor antagonist MK801 was administered to female Sprague-Dawley rats on postnatal days (PND) 5 through 14. Open-field test was performed on PND 42, and PND 77 to examine the validity of the current model. BDNF protein levels in hippocampus and prefrontal cortex (PFC) were analyzed on PND 15, PND 42, and PND 77. Results showed that neonatal challenge with MK-801 persistently elevated locomotor activity as well as BDNF expression; the alterations in BDNF expression varied at different developing stages and among brain regions. However, these findings provide neurochemical evidence that the blockade of NMDA receptors during brain development results in long-lasting alterations in BDNF expression and might contribute to neurobehavioral pathology of the present animal model for schizophrenia. Further study in the mechanisms and roles of the BDNF may lead to better understanding of the pathophysiology of schizophrenia.
Highlights
Schizophrenia is a complex and severe brain disorder with poorly defined etiology and pathophysiology
In prefrontal cortex (PFC), the brain-derived neurotrophic factor (BDNF) expression was significantly upregulated in MK-801 treated rats (t = −6.19, df = 16, and P < .001) at early time point of postnatal days (PND) 15
In contrast to the developmental pattern in PFC, BDNF expression in the hippocampus was not influenced by neonatal MK-801 administration (t = −0.30, df = 16, and P > .05) on PND 15
Summary
Schizophrenia is a complex and severe brain disorder with poorly defined etiology and pathophysiology. Neurotrophic molecules are believed to be critical in the development and function maintenance of cortical neurons and synapses, such as brain-derived neurotrophic factor (BDNF) [5]. Several lines of evidence have suggested the involvement of BDNF in pathophysiology of schizophrenia in both human and animal studies [13,14,15]. Knowledge in understanding of BDNF in pathophysiology of schizophrenia remains limited and poorly defined. One of key pitfalls of schizophrenia research in animal studies is that all experiments usually focused only on a certain period during development. It is fundamentally and clinically significant to investigate long-term changes of BDNF in animal models of schizophrenia in a development scheme
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