Cognitive dysfunction, elevated anxiety, and reduced cocaine response in circadian clock-deficient cryptochrome

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Dimitri De Bundel1, Giuseppe Gangarossa, Anne Biever

  • 1CNRS, UMR-5203, Institut de Génomique Fonctionnelle Montpellier, France ; INSERM, U661 Montpellier, France ; Universités de Montpellier 1 and 2, UMR-5203 Montpellier, France.

Frontiers in Behavioral Neuroscience
|November 5, 2013
PubMed

Insights

Deleting cryptochrome (Cry1 and Cry2) genes disrupts circadian rhythms and impacts cognitive function, increasing anxiety and reducing responses to cocaine. These findings highlight cryptochromes

Area of Science:

  • Neuroscience
  • Chronobiology
  • Genetics

Background:

  • Circadian rhythm disruptions are linked to cognitive and mood disorders, but causal links are unclear.
  • Core circadian clock genes, like cryptochromes (Cry1 and Cry2), regulate daily rhythms.
  • The precise role of cryptochromes in behavior and cognition requires further investigation.

Purpose of the Study:

  • To investigate the behavioral and cognitive effects of genetically disrupting the core circadian clock genes Cry1 and Cry2.
  • To determine the impact of combined Cry1 and Cry2 deletion versus single-gene deletion on various behaviors.

Main Methods:

  • Generation of mice lacking both Cry1 and Cry2 (Cry1(-/-)Cry2(-/-)) and mice with single-gene deletions (Cry1(-/-)Cry2(+/+) and Cry1(+/+)Cry2(-/-)).
  • Assessment of locomotor activity, recognition memory, fear memory, anxiety-related behaviors (forced swim, sucrose preference, open field, elevated plus maze), and response to cocaine.
  • Analysis of striatal extracellular signal-regulated kinase (ERK) phosphorylation.

Main Results:

  • Mice lacking both Cry1 and Cry2 showed reduced activity, impaired recognition memory, and increased anxiety.
  • Fear memory remained intact, while depression-related behaviors were unaffected.
  • Single deletion of Cry1 or Cry2 also impaired recognition memory and increased anxiety, though to varying degrees.
  • The response to cocaine, including hyperlocomotion and ERK phosphorylation, was significantly reduced in double knockout mice.

Conclusions:

  • Cryptochrome genes (Cry1 and Cry2) play a crucial role beyond circadian rhythm regulation.
  • These genes directly influence cognitive functions, anxiety-related behaviors, and psychostimulant drug sensitivity.
  • Partial or complete loss of cryptochrome function leads to specific behavioral and cognitive deficits.
Keywords:
Cry1 and Cry2 knockout micelearningmood-related disorderpsychostimulants

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