|Postmortem examinations in subjects
with schizophrenia have shown a decrease in dendritic spine density, a marker
of excitatory synapses, on basilar dendrites of layer 3 pyramidal neurons.
Additionally, brain-derived neurotrophic factor (BDNF), a secreted neurotrophin
shown to stimulate the growth of dendritic spines, is reported to be decreased
in the prefrontal cortex of subjects with schizophrenia. Therefore, it was
important to determine if the reduction in spine density observed in schizophrenia
is due to the decrease in BDNF.
Knockout of the bdnf gene was induced in mice in embryo
and at 12 weeks of age. For each experimental condition, Golgi-impregnated
pyramidal neurons located in the prelimbic and anterior cingulate regions
were measured for the total length of the basilar dendrites and the length,
diameter, and branch order of each segment. Spine density was measured
on the longest basilar dendrite. The branch photomicrographs above illustrate
Golgi-impregnated basilar dendrites and spines of pyramidal neurons in
the prelimbic cortex of A) mice with BDNF knockout induced during embryogenesis,
B) mice with BDNF knockout induced at postnatal 12 weeks, and C) wild-type
control mice. Bar = 10 μm.
Quantitative studies failed to reveal any differences across the three experimental groups for spine density or any of the dendritic measures. Therefore, in contrast to our hypothesis, a decrease in BDNF expression alone does not seem sufficient to alter basilar dendritic morphology in the prelimbic and anterior cingulate cortices of adult mice, regardless of whether the reduction in BDNF mRNA levels was induced prenatally or in early adulthood. These finding suggest that other molecular abnormalities are also required to produce the pyramidal neuron dendritic spine abnormalities observed in schizophrenia.
|Hill J, Kolluri N, Sun Z, Sampson AR, Monteggia L, Lewis DA: Analysis of pyramidal neuron morphology in an inducible knockout of brain-derived neurotrophic factor. Biol Psychiatry 57:932-934, 2005.|