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Neuroactive steroids, mood stabilizers, and neuroplasticity: alterations following lithium and changes in Bcl-2 knockout mice.

Publication ,  Journal Article
Marx, CE; Yuan, P; Kilts, JD; Madison, RD; Shampine, LJ; Manji, HK
Published in: Int J Neuropsychopharmacol
June 2008

Many neuroactive steroids (NS) demonstrate neurotrophic and neuroprotective actions, including protection against apoptosis via Bcl-2 protein. NS are altered in post-mortem brain tissue from subjects with bipolar disorder, and several agents with efficacy in mania elevate NS in rodents. We therefore hypothesized that lithium and valproate may elevate NS, and compensatory NS increases may occur in Bcl-2 knockout mice. NS levels (allopregnanolone, pregnenolone) were determined in frontal cortex by negative ion chemical ionization gas chromatography/mass spectrometry in male Wistar Kyoto rats treated chronically with lithium, valproate, or vehicle. NS were also investigated in heterozygous Bcl-2 knockout mice. Allopregnanolone levels are significantly elevated in lithium-treated (p<0.05), but not in valproate-treated, rats. Pregnenolone levels also tend to be higher following lithium treatment (p=0.09). Knockout of Bcl-2 significantly increases pregnenolone levels in mice (p<0.01), while allopregnanolone levels are unaltered. NS induction may be relevant to mechanisms contributing to lithium therapeutic efficacy and neuroprotection.

Duke Scholars

Published In

Int J Neuropsychopharmacol

DOI

ISSN

1461-1457

Publication Date

June 2008

Volume

11

Issue

4

Start / End Page

547 / 552

Location

England

Related Subject Headings

  • Valproic Acid
  • Reverse Transcriptase Polymerase Chain Reaction
  • Rats, Inbred WKY
  • Rats
  • Psychiatry
  • Pregnenolone
  • Pregnanolone
  • Prefrontal Cortex
  • Neuronal Plasticity
  • Mice, Knockout
 

Citation

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MLA
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Marx, C. E., Yuan, P., Kilts, J. D., Madison, R. D., Shampine, L. J., & Manji, H. K. (2008). Neuroactive steroids, mood stabilizers, and neuroplasticity: alterations following lithium and changes in Bcl-2 knockout mice. Int J Neuropsychopharmacol, 11(4), 547–552. https://doi.org/10.1017/S1461145708008444
Marx, Christine E., Peixiong Yuan, Jason D. Kilts, Roger D. Madison, Lawrence J. Shampine, and Husseini K. Manji. “Neuroactive steroids, mood stabilizers, and neuroplasticity: alterations following lithium and changes in Bcl-2 knockout mice.Int J Neuropsychopharmacol 11, no. 4 (June 2008): 547–52. https://doi.org/10.1017/S1461145708008444.
Marx CE, Yuan P, Kilts JD, Madison RD, Shampine LJ, Manji HK. Neuroactive steroids, mood stabilizers, and neuroplasticity: alterations following lithium and changes in Bcl-2 knockout mice. Int J Neuropsychopharmacol. 2008 Jun;11(4):547–52.
Marx, Christine E., et al. “Neuroactive steroids, mood stabilizers, and neuroplasticity: alterations following lithium and changes in Bcl-2 knockout mice.Int J Neuropsychopharmacol, vol. 11, no. 4, June 2008, pp. 547–52. Pubmed, doi:10.1017/S1461145708008444.
Marx CE, Yuan P, Kilts JD, Madison RD, Shampine LJ, Manji HK. Neuroactive steroids, mood stabilizers, and neuroplasticity: alterations following lithium and changes in Bcl-2 knockout mice. Int J Neuropsychopharmacol. 2008 Jun;11(4):547–552.
Journal cover image

Published In

Int J Neuropsychopharmacol

DOI

ISSN

1461-1457

Publication Date

June 2008

Volume

11

Issue

4

Start / End Page

547 / 552

Location

England

Related Subject Headings

  • Valproic Acid
  • Reverse Transcriptase Polymerase Chain Reaction
  • Rats, Inbred WKY
  • Rats
  • Psychiatry
  • Pregnenolone
  • Pregnanolone
  • Prefrontal Cortex
  • Neuronal Plasticity
  • Mice, Knockout