Analysis of pyramidal neuron morphology in an inducible knockout of brain-derived neurotrophic factor

Abstract

The messenger ribonucleic acid (mRNA) for brain-derived neurotrophic factor (BDNF), a regulator of pyramidal neuron dendritic spine density during development, is decreased in the prefrontal cortex of subjects with schizophrenia, and the level of BDNF mRNA expression is positively correlated with dendritic spine density in the same subjects. To determine whether reduced BDNF mRNA expression might account for decreased spine density in schizophrenia, a knockout of the BDNF gene was induced in mice during embryogenesis or at 12 weeks of age. Quantitative assessments were made of the dendritic arbor of Golgi-impregnated pyramidal neurons in the prelimbic and anterior cingulate cortices in adulthood. Despite an 80% reduction in BDNF mRNA levels in both knockouts, neither spine density nor other dendritic or somal measures were decreased compared with wild-type animals. A reduction in BDNF expression alone does not seem to be sufficient to alter pyramidal neuron morphology in mice. This finding suggests that other molecular abnormalities are also required to produce the pyramidal neuron dendritic spine abnormalities observed in schizophrenia.