Phosphodiesterase type 5 (PDE5) inhibition improves object recognition memory: indications for central and peripheral mechanisms

A promising target for memory improvement is phosphodiesterase type 5 (PDE5), which selectively hydrolyzes cyclic guanosine monophosphate (cGMP). In rodents, PDE5 inhibitors (PDE5-Is) have been shown to improve memory performance in many behavioral paradigms. However, it is questioned whether the positive effects in animal studies result from PDE5 inhibition in the central nervous system or the periphery. Therefore, we studied the effects of PDE5 inhibition on memory and determined whether compound penetration of the blood-brain barrier (BBB) is required for this activity. Two selective PDE5-Is, vardenafil and UK-343,664, were tested in the object recognition task (ORT) in both a MK-801- and scopolamine-induced memory deficit model, and a time-delay model without pharmacological intervention. Compounds were dosed 30 min before the learning trial of the task. To determine if the PDE5-Is crossed the BBB, their concentrations were determined in plasma and brain tissue collected 30 min after oral administration. Vardenafil improved object recognition memory in all three variants of the ORT. UK-343,664 was ineffective at either preventing MK-801-induced memory disruption or time-dependent memory decay. However, UK-343,664 attenuated the memory impairment of scopolamine. Vardenafil crossed the BBB whereas UK-343,664 did not. Further, co-administration of UK-343,664 and scopolamine did not alter the brain partitioning of either molecule. This suggests that the positive effect of UK-343,664 on scopolamine-induced memory decay might arise from peripheral PDE5 inhibition. The results herein suggest that there may be multiple mechanisms that mediate the efficacy of PDE5 inhibition to improve memory performance in tasks such as the ORT and that these involve PDE5 located both within and outside of the brain. To further elucidate the underlying mechanisms, the cellular and subcellular localization of PDE5 needs to be determined.     

Illness perceptions and self-care behaviours in the first years of living with type 2 diabetes; does the presence of complications matter?

Objective: To assess illness perceptions, self-care behaviours and their relationship in recently diagnosed type 2 diabetes mellitus (T2DM) patients with and without diabetes-related complications.

Design: Cross-sectional survey among 192 recently diagnosed T2DM patients of whom 23% reported the presence of diabetes-related complications. Illness perceptions and self-care were assessed by the Revised Illness Perception Questionnaire (IPQ-R) and the revised Summary of Diabetes Self-Care Activities (SDSCA) measure.

Results: Generally, participating patients perceived T2DM as a chronic, but relatively controllable condition with minor consequences. In the presence of complications, however, T2DM was perceived as more unpredictable with more (serious) consequences and less controllable by self-care or medical treatment. Furthermore, engagement in exercise and foot care was reported more often by patients with complications. Self-care was related to certain illness perception dimensions, and interactions between perceptions and complications were found.

Conclusion: T2DM patients in the first years of their illness are often recommended to make lifestyle changes in the absence of noticeable diabetes-related symptoms or complaints. As many T2DM patients do not seem to perceive their condition to be serious and postpone lifestyle changes until diabetes-related complications appear, a major challenge for professionals is to convince asymptomatic patients of the importance of self-care.     

Sub-chronic rolipram treatment leads to a persistent improvement in long-term object memory in rats

In the present study the effects of sub-chronic rolipram treatment in an object recognition task in 3-month-old male rats were investigated. Rats remember which object they have explored in a previous trial (T1) when they are tested 1 h later (T2). However, when tested 24 h later, they do not remember which object was presented to them in the first trial. Drug treatments may improve discrimination performance after 24 h, i.e., improve memory for the familiar object. Rats were sub-chronically treated with 0.5 mg/kg rolipram (p.o.) for five consecutive days and tested with a 24 h delay between T1 and T2. Memory performance in the object recognition task was assessed before, during and after sub-chronic treatment. In addition, we investigated whether the timing of the final dose, i.e., 24, 1, or 6 h before training, had an effect on memory performance. During sub-chronic treatment, i.e., after 2-3 days of rolipram treatment, moderate effects on memory performance were observed. Regardless of when the final administration was given, sub-chronic rolipram treatment improved long-term memory performance. Since plasma and brain rolipram levels were undetectable at 24 h before the test, and acute treatment with rolipram 24 h before training had no effects, the observed memory enhancement cannot be attributed to acute rolipram effects. The long-term memory enhancing effects of rolipram might be explained by long-lasting neuronal changes by the chronic treatment due to recurring activation of the cAMP/PKA/CREB pathway leading to CREB phosphorylation.