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Related Experiment Videos

Antidepressant effects on kinase gene expression patterns in rat brain.

J L Rausch1, C F Gillespie, Y Fei

  • 1Veterans Administration, Medical College of Georgia, Augusta, GA 30912, USA. jeffreyr@mail.mcg.edu

Neuroscience Letters
|November 19, 2002
PubMed
Summary

Chronic SSRI treatment downregulates specific protein kinases (PKs) involved in serotonin transporter (SERT) regulation. This decrease in PK expression may represent a homeostatic mechanism to manage extracellular serotonin levels.

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Area of Science:

  • Neuropharmacology
  • Molecular Biology
  • Biochemistry

Background:

  • Serotonin transporter (SERT) regulates extracellular serotonin levels.
  • Multiple kinase pathways are implicated in SERT regulation.
  • Selective serotonin reuptake inhibitors (SSRIs) are widely used antidepressants.

Purpose of the Study:

  • To investigate the hypothesis that chronic SSRI administration decreases kinase expression.
  • To understand the role of kinase downregulation in SERT homeostasis.

Main Methods:

  • Whole brain kinase mRNA expression was analyzed using Affymetrix gene chips in rats.
  • Rats were treated with placebo, fluoxetine (acute and chronic), or citalopram (chronic).

Main Results:

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  • Chronic fluoxetine and citalopram treatment led to the downregulation of specific kinases, including Protein Kinase C (PKC)-delta and -gamma, stress-activated protein kinase, cAMP-dependent protein kinase beta isoform, Janus protein kinase, and phosphofructokinase M.
  • Acute fluoxetine treatment did not result in significant kinase downregulation.
  • These changes were observed after 21 days of chronic treatment.

Conclusions:

  • The findings support the hypothesis that chronic SSRI administration downregulates key protein kinases.
  • This downregulation of protein kinases is consistent with a homeostatic mechanism for regulating SERT function and extracellular serotonin.