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Behavioral characterization of CD26 deficient mice in animal tests of anxiety and antidepressant-like activity
Malika El Yacoubi1, Jean-Marie Vaugeois, Didier Marguet
1FRE 2735 CNRS, IFRMP 23, UFR de Médecine & Pharmacie, Rouen, France.
Abstract:
CD26 exhibits a dipeptidylpeptidase-IV function (DPPIV) which regulates neuropeptide activity by N-terminal processing. Because abnormal plasma DPPIV was associated in mammals with behavioral changes, we examined the behavior of CD26-/- mice resulting from targeted inactivation of the gene. These animals had a decreased immobility in the forced swim and tail suspension tests, indicating a reduced depression-like behavior. We addressed some factors that could affect these results. No major differences between mutants and controls were observed in the black/white box test that investigates anxiety. In the hole-board apparatus that explores both curiosity and anxiety, CD26-/- mice of both genders made significantly more head dips than controls. In a motor activity test, mutants displayed higher horizontal and vertical activities i.e. increased novelty-induced behavioral activation. We conclude that DPPIV inactivation in mice broadly leads to an antidepressant-like and hyperactive phenotype.
Insights
Mice lacking CD26 (dipeptidylpeptidase-IV) showed reduced depression-like behaviors and increased activity. This suggests CD26 plays a role in regulating mood and behavior.
Area of Science:
- Neuroscience
- Biochemistry
- Genetics
Background:
- CD26, also known as dipeptidylpeptidase-IV (DPPIV), is an enzyme involved in neuropeptide regulation.
- Abnormal DPPIV levels in mammals have been linked to behavioral alterations.
Purpose of the Study:
- To investigate the behavioral effects of CD26 deficiency by studying CD26 knockout (CD26-/-) mice.
- To determine the impact of DPPIV inactivation on depression-like behavior, anxiety, curiosity, and motor activity.
Main Methods:
- Behavioral analysis of CD26-/- mice and wild-type controls using forced swim, tail suspension, black/white box, hole-board, and motor activity tests.
- Targeted gene inactivation to create CD26-/- mice.
Main Results:
- CD26-/- mice exhibited significantly decreased immobility in forced swim and tail suspension tests, indicative of reduced depression-like behavior.
- No significant differences in anxiety were observed in the black/white box test.
- CD26-/- mice showed increased head dips in the hole-board test and higher horizontal and vertical activity in motor tests, suggesting increased curiosity and novelty-induced activation.
Conclusions:
- DPPIV inactivation in mice results in an antidepressant-like phenotype.
- CD26 deficiency leads to a hyperactive phenotype with increased exploratory behavior and response to novelty.

