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The induction of cyclic nucleotide phosphodiesterase 4 gene (PDE4D) impairs memory in a water maze task.
Behav Brain Res. 2004 Sep 23; 154(1):99-106.BB

Abstract

In this study, the effects on memory of intraperitoneal post-training administration of cyclic nucleotide phosphodiesterase (PDE) inhibitors, DC-TA 46 and rolipram, were tested using a visible/hidden-platform water maze task. The effects of these compounds on cyclic nucleotide levels in the hippocampal formation (HF) and striatum (CP) were also assessed, by enzymatic immunoassay (EIA). The results obtained from rats trained in the visible-platform task were not significantly different from controls. On the contrary, the animals trained in the hidden-platform water maze task showed a memory impairment, when injected with DC-TA 46 at maximal dose of 20mg/kg and with rolipram at 3 and 30 mg/kg doses. The effects of these drugs on cyclic nucleotide levels in HF and CP were observed at 30 min and at 24h after drug administration. Thirty minutes after drug injection, we observed an increase of cAMP level, both in HF and in CP. Twenty-four hours after the retention test, we observed that in CP the cAMP intracellular level remained high, while in the HF at effective doses both inhibitors induced cAMP PDE activity, determining a decrease of cyclic nucleotide. Semi-quantitative RT-PCR analysis, together with Western blot immunodetection, showed a mRNA and protein induction of PDE4D PDE isoforms, that may account for the increase of PDE activity observed. Our data suggest that, despite cyclic nucleotide increase at 30 min, the fundamental event causing memory impairment, came from the subsequent long time decrease of cAMP levels, due to the post-translational PDE4D induction.

Authors+Show Affiliations

Department of Basic and Applied Biology, University of L'Aquila, Via Vetoio, località Coppito, 67100 L'Aquila, Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15302115

Citation

Giorgi, Mauro, et al. "The Induction of Cyclic Nucleotide Phosphodiesterase 4 Gene (PDE4D) Impairs Memory in a Water Maze Task." Behavioural Brain Research, vol. 154, no. 1, 2004, pp. 99-106.
Giorgi M, Modica A, Pompili A, et al. The induction of cyclic nucleotide phosphodiesterase 4 gene (PDE4D) impairs memory in a water maze task. Behav Brain Res. 2004;154(1):99-106.
Giorgi, M., Modica, A., Pompili, A., Pacitti, C., & Gasbarri, A. (2004). The induction of cyclic nucleotide phosphodiesterase 4 gene (PDE4D) impairs memory in a water maze task. Behavioural Brain Research, 154(1), 99-106.
Giorgi M, et al. The Induction of Cyclic Nucleotide Phosphodiesterase 4 Gene (PDE4D) Impairs Memory in a Water Maze Task. Behav Brain Res. 2004 Sep 23;154(1):99-106. PubMed PMID: 15302115.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The induction of cyclic nucleotide phosphodiesterase 4 gene (PDE4D) impairs memory in a water maze task. AU - Giorgi,Mauro, AU - Modica,Anna, AU - Pompili,Assunta, AU - Pacitti,Claudio, AU - Gasbarri,Antonella, PY - 2003/11/21/received PY - 2004/01/26/revised PY - 2004/01/28/accepted PY - 2004/8/11/pubmed PY - 2004/12/16/medline PY - 2004/8/11/entrez SP - 99 EP - 106 JF - Behavioural brain research JO - Behav Brain Res VL - 154 IS - 1 N2 - In this study, the effects on memory of intraperitoneal post-training administration of cyclic nucleotide phosphodiesterase (PDE) inhibitors, DC-TA 46 and rolipram, were tested using a visible/hidden-platform water maze task. The effects of these compounds on cyclic nucleotide levels in the hippocampal formation (HF) and striatum (CP) were also assessed, by enzymatic immunoassay (EIA). The results obtained from rats trained in the visible-platform task were not significantly different from controls. On the contrary, the animals trained in the hidden-platform water maze task showed a memory impairment, when injected with DC-TA 46 at maximal dose of 20mg/kg and with rolipram at 3 and 30 mg/kg doses. The effects of these drugs on cyclic nucleotide levels in HF and CP were observed at 30 min and at 24h after drug administration. Thirty minutes after drug injection, we observed an increase of cAMP level, both in HF and in CP. Twenty-four hours after the retention test, we observed that in CP the cAMP intracellular level remained high, while in the HF at effective doses both inhibitors induced cAMP PDE activity, determining a decrease of cyclic nucleotide. Semi-quantitative RT-PCR analysis, together with Western blot immunodetection, showed a mRNA and protein induction of PDE4D PDE isoforms, that may account for the increase of PDE activity observed. Our data suggest that, despite cyclic nucleotide increase at 30 min, the fundamental event causing memory impairment, came from the subsequent long time decrease of cAMP levels, due to the post-translational PDE4D induction. SN - 0166-4328 UR - https://www.unboundmedicine.com/medline/citation/15302115/The_induction_of_cyclic_nucleotide_phosphodiesterase_4_gene__PDE4D__impairs_memory_in_a_water_maze_task_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0166432804000427 DB - PRIME DP - Unbound Medicine ER -