2. Academic Validation
  3. Treatment with the selective PDE4B inhibitor A-33 or PDE4D inhibitor zatolmilast prevents sleep deprivation-induced deficits in spatial pattern separation

Treatment with the selective PDE4B inhibitor A-33 or PDE4D inhibitor zatolmilast prevents sleep deprivation-induced deficits in spatial pattern separation

  • Behav Brain Res. 2023 Dec 4:114798. doi: 10.1016/j.bbr.2023.114798.
Hongyu Zhao 1,  Arjan Blokland 1,  Jos Prickaerts 2,  Robbert Havekes 3,  Pim R A Heckman 4
Affiliations

Affiliations

  • 1 Dept. Neuropsychology & Psychopharmacology, Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, the Netherlands.
  • 2 Department of Psychiatry & Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, Maastricht, the Netherlands.
  • 3 Neurobiology Expert Group, Groningen Institute for Evolutionary Life Sciences (GELIFES), University of Groningen, Groningen, the Netherlands.
  • 4 Dept. Neuropsychology & Psychopharmacology, Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, the Netherlands. Electronic address: [email protected].
PMID: 38056709 DOI: 10.1016/j.bbr.2023.114798
Abstract

Sleep deprivation (SD) disrupts hippocampus-dependent memory, particularly in the dentate gyrus (DG) region, an area crucial for pattern separation. Previous research showed that non-selective phosphodiesterase type 4 (PDE4) inhibitors like roflumilast can alleviate these deficits. However, it remains unclear whether these outcomes are specific to a particular subfamily of PDE4. Hence, this study examined the specific impact of PDE4B inhibitor (A-33) and PDE4D inhibitor (zatolmilast) on spatial pattern separation in sleep deprived mice. Results demonstrated that SD impairs pattern separation, but both zatolmilast and A-33 alleviate these effects. However, A-33 impaired pattern separation in non-sleep deprived Animals. The cognitive benefits of these inhibitors after SD may arise from alterations in relevant signaling pathways in the DG. This study provides initial evidence that inhibiting PDE4B or PDE4D holds promise for mitigating memory deficits due to SD.

Keywords

Pattern separation; phosphodiesterase type 4; sleep deprivation.

Figures
Products