title: Tyrosine kinase B protein expression is reduced in the cerebellum of patients with bipolar disorder.
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.
  
  
  CONCLUSIONS
  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.
authors: Department of Psychiatry, School of Medicine, University of California, San Diego, La Jolla, California 92093-0603, USA.
authors: Benchawanna
authors: B
authors: Soontornniyomkij
authors: Ian P
authors: IP
authors: Everall
authors: Gursharan
authors: G
authors: Chana
authors: Ming T
authors: MT
authors: Tsuang
authors: Cristian L
authors: CL
authors: Achim
authors: Virawudh
authors: V
authors: Soontornniyomkij
references: J Neurochem. 2010 May;113(4):952-64
references: 20193039
references: J Neuropsychiatry Clin Neurosci. 2000 Spring;12(2):193-8
references: 11001597
references: Biol Psychiatry. 1996 Oct 15;40(8):726-30
references: 8894064
references: Schizophr Res. 2008 Mar;100(1-3):270-80
references: 18243664
references: Proc Natl Acad Sci U S A. 1996 Sep 3;93(18):9985-90
references: 8790444
references: Neuroreport. 2001 Oct 29;12(15):3257-62
references: 11711867
references: Biol Psychiatry. 2008 Jul 15;64(2):81-8
references: 18395701
references: Nat Rev Neurosci. 2006 Jul;7(7):511-22
references: 16791141
references: J Neurosci. 1997 Apr 15;17(8):2683-90
references: 9092589
references: Trends Mol Med. 2007 Feb;13(2):54-63
references: 17207662
references: Schizophr Bull. 2008 Jan;34(1):155-72
references: 17562694
references: Nat Rev Neurosci. 2008 Apr;9(4):304-13
references: 18319727
references: J Psychiatry Neurosci. 2011 May;36(3):195-203
references: 21223646
references: Nat Rev Neurosci. 2005 Apr;6(4):312-24
references: 15803162
references: Nature. 2003 Nov 6;426(6962):74-8
references: 14603320
references: Nat Neurosci. 2002 Mar;5(3):225-33
references: 11836532
references: Schizophr Res. 2005 Jan 1;72(2-3):109-22
references: 15560956
references: Psychiatry Res. 2010 Jul 30;178(2):374-80
references: 20488553
references: J Neurosci. 2005 Jan 12;25(2):372-83
references: 15647480
references: Prog Neurobiol. 2001 Jan;63(1):71-124
references: 11040419
references: J Psychiatr Res. 2007 Dec;41(12):979-90
references: 17239400
references: Mol Psychiatry. 2003 Jun;8(6):592-610
references: 12851636
references: Age (Dordr). 2010 Sep;32(3):309-22
references: 20422297
references: J Chem Neuroanat. 2003 Mar;25(3):175-83
references: 12706205
references: Gene Expr Patterns. 2004 May;4(3):257-61
references: 15053973
references: Neuroscience. 1999;88(4):1015-32
references: 10336117
references: Curr Neuropharmacol. 2009 Dec;7(4):276-85
references: 20514207
references: Mol Psychiatry. 2000 May;5(3):293-300
references: 10889532
references: Brain Res Dev Brain Res. 1999 Jan 11;112(1):21-9
references: 9974156
references: Prog Neurobiol. 2005 Jun;76(2):99-125
references: 16099088
references: Prog Neuropsychopharmacol Biol Psychiatry. 2003 Aug;27(5):801-7
references: 12921913
references: Schizophr Res. 2001 Oct 1;52(1-2):79-86
references: 11595394
references: Nat Neurosci. 2000 Apr;3(4):342-9
references: 10725923
references: Neuroscience. 2010 Jan 20;165(2):485-91
references: 19861148
references: Arch Gen Psychiatry. 2000 Nov;57(11):1061-9
references: 11074872
references: J Psychiatry Neurosci. 2005 May;30(3):178-86
references: 15944742
references: Bipolar Disord. 2009 Feb;11(1):19-32
references: 19133963
references: Endocrine. 2007 Apr;31(2):167-73
references: 17873329
references: Arch Gen Psychiatry. 2009 Jan;66(1):22-32
references: 19124685
references: Dev Neurobiol. 2010 Apr;70(5):271-88
references: 20186709
references: Dev Neurobiol. 2009 Sep 1;69(10):647-62
references: 19551874
references: Brain Res Rev. 2006 Sep;52(2):293-304
references: 16759710
references: Schizophr Res. 2000 Aug 3;44(2):151-5
references: 10913747
references: Am J Pathol. 2006 Aug;169(2):528-43
references: 16877354
references: Am J Psychiatry. 2006 Oct;163(10):1829-31
references: 17012697
references: Brain Pathol. 2006 Oct;16(4):320-32
references: 17107602