Effect of antipsychotic drugs on brain‐derived neurotrophic factor expression under reduced N‐methyl‐D‐aspartate receptor activity

Abstract

Brain-derived neurotrophic factor (BDNF) promotes a variety of neuromodulatory processes during development as well as in adulthood. This neurotrophin has been associated with synaptic plasticity, suggesting that its regulation may represent one of the mechanisms through which psychotropic drugs alter brain function. Because reduced glutamatergic function represents a major feature of schizophrenia, we investigated the effects of the concomitant administration of haloperidol or olanzapine with the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 on BDNF expression. MK-801 reduces the hippocampal expression of the neurotrophin; this effect was exacerbated by haloperidol, but it was normalized by olanzapine. Our data reveal a fine tuning of BDNF biosynthesis and a differential modulation by antipsychotic drugs when NMDA-mediated transmission is reduced, suggesting that haloperidol and olanzapine can produce different effects on brain plasticity through the modulation of BDNF expression.

Specificity and timing of neocortical transcriptome changes in response to BDNF gene ablation during embryogenesis or adulthood

“…83 In addition, various animal models of schizophrenia consistently show a downregulation of BDNF transcript or protein. 4,[75][76][77][78][84][85][86][87][88] Importantly, just as in our current study of BDNF- ablated animals, SST, NPY and RGS4 transcripts are downregulated in the prefrontal cortex (PFC) of subjects with schizophrenia. 29,89,90 However, we acknowledge that other, BDNF-independent mechanisms may also account for the altered expression of these genes in schizophrenia.…”

Voluntary wheel running ameliorates symptoms of MK-801-induced schizophrenia in mice

“…Of note, BDNF expression in the hippocampus is suppressed by traumatic brain injury, suggesting that BDNF exerts a neuroprotective effect (36). The NMDA receptor antagonist MK-801 also suppresses hippocampal expression of BDNF (37). Decreased BDNF expression has been identified in several mental disorders, including schizophrenia and depression (26,38).…”

BDNF in schizophrenia, depression and corresponding animal models

“…10,11 Administration of the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 reduces the hippocampal expression of BDNF. 12 Young rats exposed to MAM on gestational day 12 showed deficits in both the acquisition and retention phases of the Morris maze, and these changes were associated with significant decreases in NGF and BDNF in the hippocampus. 13 A link between administration of antipsychotic drugs in rats and tissue levels of BDNF has been reported.…”

“…Reduced BDNF mRNA in the prefrontal cortex and hippocampus in animals with neonatal ibotenic acid lesions of the ventral hippocampus 10,11 Administration of the NNMDA receptor antagonist MK-801 reduces the hippocampal expression of BDNF 12 Rats prenatally exposed to antiproliferative agent MAM show behavioral deficits associated with significant decreases in BDNF in the hippocampus 13 Mice with knockout of the trkB receptor present behavioral symptoms similar to those of mouse models of schizophrenic-like disorder 14 Table 2 Summary of the main findings supporting the hypothesis of BDNF involvement in depression in humans and animal models Human Decreased plasma levels of BDNF in patients with major depression 15 Increased BDNF immunoreactivity in the hippocampus of post-mortem tissue from patients treated with antidepressant drugs 16 …”