Sub-efficacious doses of phosphodiesterase 4 and 5 inhibitors improve memory in a mouse model of Alzheimer's disease.

Sub-efficacious doses of phosphodiesterase 4 and 5 inhibitors improve memory in a mouse model of Alzheimer's disease. Neuropharmacology. 2018 Jun 06;: Authors: Gulisano W, Tropea MR, Arancio O, Palmeri A, Puzzo D Abstract Cyclic nucleotides cAMP and cGMP cooperate to ensure memory acquisition and consolidation. Increasing their levels by phosphodiesterase inhibitors (PDE-Is) enhanced cognitive functions and rescued memory loss in different models of aging and Alzheimer's disease (AD). However, side effects due to the high doses used limited their application in humans. Based on previous studies suggesting that combinations of sub-efficacious doses of cAMP- and cGMP-specific PDE-Is improved synaptic plasticity and memory in physiological conditions, here we aimed to study whether this treatment was effective to counteract the AD phenotype in APPswe mice. We found that a 3-week chronic treatment with a combination of sub-efficacious doses of the cAMP-specific PDE4-I roflumilast (0.01 mg/kg) and the cGMP-specific PDE5-I vardenafil (0.1 mg/kg) improved recognition, spatial and contextual fear memory. Importantly, the cognitive enhancement persisted for 2 months beyond administration. This long-lasting action, and the possibility to minimize side effects due to the low doses used, might open feasible therapeutic strategies against AD. PMID: 29885420 [PubMed - as supplied by publisher]
Source: Neuropharmacology - Category: Drugs & Pharmacology Authors: Tags: Neuropharmacology Source Type: research

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CONCLUSIONS: Our analysis on these individuals lead to several interesting observations together suggesting that AD risk factors comprise a network of interlocking feedback loops that may be modifiable. Our findings indicate previously unidentified connectivity between AD risk factors, suggesting that treatment regimens should be tailored to the individual and multi-modal to simultaneously return several risk factors to a normative state. If successfully performed, the possibility to slow progression of AD and possibly reverse aspects of cognitive decline may become achievable. PMID: 30338750 [PubMed - as supplied by publisher]
Source: Current Aging Science - Category: Geriatrics Tags: Curr Aging Sci Source Type: research
This study is part of a growing body of research that suggests a sleep-deprived brain might be more vulnerable to Alzheimer’s disease. Animal studies have shown levels of plaque-forming A-beta plummet during sleep. Other research points to the fact that a sleeping brain runs the “clean cycle” (a reference to a dishwasher) to remove the day’s metabolic debris, specifically A-beta plaques. A study done in 2017 found that even one sleepless night appears to leave behind an excess of the troublesome protein fragment. While this is all impressive research, scientists believe there are still plenty of gap...
Source: World of Psychology - Category: Psychiatry & Psychology Authors: Tags: Aging Alzheimer's Health-related Mental Health and Wellness Research Sleep Alzheimer's disease Dementia Source Type: blogs
Diagnosed with Alzheimer’s at age 53, Hazel has been living with the disease for more than 18 years. Her early years were grim even as she fought to do everything she could to improve her health. She used a wheelchair much of time. Then, while attending a bridal show, she stopped to rest at the table of professional dancer Chris Ingram. Ingram asked her if she’d like to learn how to dance. Hazel’s response was what one would expect. “How can I dance when I can’t even walk?”  Ingram just told her to stop by the World Champion Productions Dance Studio and see. Read the full arti...
Source: Minding Our Elders - Category: Geriatrics Authors: Source Type: blogs
Middle-aged and worried about your memory slips? You probably don’t have dementia. The majority of the memory slips that concern this age group, and even those significantly older, are due to stress and other factors rather than impending dementia. However, researchers have now found that people who are suffering from memory loss but are unaware of their problem are most likely developing the disease. Read the full article on HealthCentral about awareness and memory loss - and how lack of  this awareness can point to developing dementia: MedicareFAQ – Medicare Resource Center Support a caregiver or jump-st...
Source: Minding Our Elders - Category: Geriatrics Authors: Source Type: blogs
Molecules, Vol. 23, Pages 2663: Design, Synthesis of N-phenethyl Cinnamide Derivatives and Their Biological Activities for the Treatment of Alzheimer’s Disease: Antioxidant, Beta-amyloid Disaggregating and Rescue Effects on Memory Loss Molecules doi: 10.3390/molecules23102663 Authors: Tian Chai Xiao-Bo Zhao Wei-Feng Wang Yin Qiang Xiao-Yun Zhang Jun-Li Yang Gx-50 is a bioactive compound for the treatment of Alzheimer’s disease (AD) found in Sichuan pepper (Zanthoxylum bungeanum). In order to find a stronger anti-AD lead compound, 20 gx-50 (1–20) analogs have been designed and syn...
Source: Molecules - Category: Chemistry Authors: Tags: Article Source Type: research
Abstract Emerging evidence indicates that moderate intensity aerobic exercise is positively correlated with cognitive function and memory. However, the exact mechanisms underlying such improvements remain unclear. Recent research in animal models allows proposition of a pathway in which brain-derived neurotrophic factor (BDNF) is a key mediator. This perspective draws upon evidence from animal and human studies to highlight such a mechanism whereby exercise drives synthesis and accumulation of neuroactive metabolites such as myokines and ketone bodies in the periphery and in the hippocampus to enhance BDNF express...
Source: Ageing Research Reviews - Category: Genetics & Stem Cells Authors: Tags: Ageing Res Rev Source Type: research
This study was conducted to assess if curcumin prevents retrieval deficit induced by scopolamine in passive avoidance task. Moreover, according to the proposed link between cholinergic system and Akt/GSK-3β (Glycogen synthase kinase 3 beta) signaling, the hippocampal contents of these proteins were determined. Male NMRI mice (20-25g body weight) were treated with 50 or 100mg/kg/po curcumin or its vehicle for 10 days. On day 10, the animals were trained in passive avoidance apparatus. The retention trial was performed 24h later. Scopolamine (1mg/kg/i.p.) or its vehicle was administered 30min before retention test. At t...
Source: European Journal of Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Eur J Pharmacol Source Type: research
Abstract Based on the quantitative structure-activity relationship (QSAR), some novel p-aminobenzoic acid derivatives as promising cholinesterase enzyme inhibitors were designed, synthesized, characterized and evaluated to enhance learning and memory. The in vitro enzyme kinetic study of the synthesized compounds revealed the type of inhibition on the respective acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes. The in vivo studies of the synthesized compounds exhibited significant reversal of cognitive deficits in the animal models of amnesia as compared to standard drug donepezil. Further, the...
Source: Bioorganic Chemistry - Category: Chemistry Authors: Tags: Bioorg Chem Source Type: research
Abstract BACKGROUND: Presence of blood brain barrier is one of the major hurdle in drug delivery to brain for the treatment of neurological diseases. Alternative and more effective drug delivery approaches have been investigated for the drug targeting to brain in therapeutic range. OBJECTIVE: The present investigation was carried out to improve the galantamine bioavailability in brain by intranasal drug delivery through thiolated chitosan nanoparticles and compared to nasal and oral delivery of its solution using pharmacodynamic activity as well as biochemical estimation. METHOD: Thiolated chitosan (modi...
Source: Current Drug Delivery - Category: Drugs & Pharmacology Authors: Tags: Curr Drug Deliv Source Type: research
AbstractAccording to the recent study, world-wide 40 million patients are affected by Alzheimer disease (AD) because it is one of the dangerous neurodegenerative disorders. This AD disease has less symptoms such as short term memory loss, mood swings, problem with language understanding and behavioral issues. Due to these low symptoms, AD disease is difficult to recognize in the early stage. So, the automated computer aided system need to be developed for recognizing the AD disease for minimizing the mortality rate. Initially, brain MRI image is collected from patients which are processed by applying different processing s...
Source: Journal of Medical Systems - Category: Information Technology Source Type: research
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