Phosphodiesterase inhibition improves cognitive deficit

Newsletter # 93

Animal models

Many studies have demonstrated that deficiency in cAMP and cGMP signaling is involved in various cognitive disorders including Alzheimer's disease and schizophrenia. Indeed, the above cyclic nucleotides play essential role in neuroplasticity and neuroprotection. Thus, phosphodiesterase (PDE) inhibitions that prevents cAMP and/or cGMP degradation have shown growing interest as possible targets for treatment of cognitive disorders.

Roflumilast and Sildenafil are widely used PDE inhibitor drugs (4 and 5 family, respectively) with known side effect profiles. They have been demonstrated to improve cognitive function in different clinical trials.

  • In line with clinical findings, NEUROFIT preclinical data show that a single acute treatment with or with Roflumilast or with Sildenafil markedly reverses scopolamine-induced cognitive deficit in the mouse spontaneous alternation paradigm.
    Altogether, the above findings further support the potential benefits of PDE inhibition mechanism for the treatment of cognitive disorders.


  • Roflumilast improves cognitive deficit in mice


    NEUROFIT website

    *** , statistically significant as compared to the Placebo/Scopolamine condition

  • Sildenafil  improves cognitive deficit in mice


    NEUROFIT website

    *** , statistically significant as compared to the Placebo/Scopolamine condition


  • The graphs show the cognitive performance of mice as measured by their spontaneous alternation in the T-maze. Scopolamine-induced deficit is evidenced by the decrease in the spontaneous alternation of mice (white vs black column), because of repetitive insistence (stereotypy) on the visit of the same arm of the T-maze. The decrease in the alternation reflects stereotypic and repetitive behavior, a common symptom in dementia patients. (DOI: 10.1177/1533317513481094)
    Acute administration of (left panel) or (right panel) normalizes the spontaneous alternation performance of scopolamine mice, hence reflects an improved cognitive ability (Black vs colored columns).

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