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J Affect Disord. 2011 Oct;133(3):646-54. doi: 10.1016/j.jad.2011.04.044. Epub 2011 May 25.

Tyrosine kinase B protein expression is reduced in the cerebellum of patients with bipolar disorder.

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1
Department of Psychiatry, School of Medicine, University of California, San Diego, La Jolla, California 92093-0603, USA.

Abstract

BACKGROUND:

The role of the cerebellum in coordinating mental activity is supported by its connections with cerebral regions involved in cognitive/affective functioning, with decreased activities on functional neuroimaging observed in the cerebellum of schizophrenia patients performing mental tasks. Brain-derived neurotrophic factor (BDNF)-induced activation of tyrosine kinase B (TrkB) is essential to synaptic plasticity. We hypothesized that alterations in BDNF and TrkB expression in the cerebellum were associated with schizophrenia and affective disorders.

METHODS:

We employed immunohistochemistry and immunoblotting to quantify protein expression of BDNF and TrkB in the cerebellum of patients with schizophrenia, bipolar disorder, and major depression compared to controls (n=15 each).

RESULTS:

While TrkB immunoreactivity in each of the molecular and granule-cell layers was reduced in all 3 disease groups (12-34%) compared to the control (P=0.018 and 0.038, respectively, ANOVA), only the reduction in bipolar disorder remained statistically significant upon Tukey-Kramer post hoc analyses (P=0.019 and 0.021, respectively). Apparent decreases in BDNF immunoreactivity in all 3 disease groups (12-30%) compared to the control were not statistically significant. TrkB immunoreactivity was not significantly associated with any of the demographic, clinical, and postmortem variables. Immunoblotting displayed an 85-kDa TrkB-immunoreactive band, consistent with a truncated isoform, in all 60 cases.

LIMITATIONS:

On immunoblotting, apparent decreases in 85-kDa-TrkB levels in all 3 disease groups compared to the control were not statistically significant.

CONCLUSIONS:

Our finding of reduced TrkB expression in bipolar disorder suggests that dysregulation of TrkB-mediated neurotrophin signaling in the cerebellum may play a role in the pathophysiology of this disease.

PMID:
21612826
PMCID:
PMC3163025
DOI:
10.1016/j.jad.2011.04.044
[Indexed for MEDLINE]
Free PMC Article

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