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Inhibitor of Phosphodiestearse-4 improves memory deficits, oxidative stress, neuroinflammation and neuropathological alterations in mouse models of dementia of Alzheimer’s Type
- Source :
- Biomedicine & Pharmacotherapy. 88:698-707
- Publication Year :
- 2017
- Publisher :
- Elsevier BV, 2017.
-
Abstract
- The study investigates the potential of Rolipram a phosphodiesterase-4 inhibitor in cognitive deficits induced by streptozotocin (STZ, 3mg/kg intracerebroventricularly) and natural ageing in mice. Morris water maze (MWM) test was employed to evaluate learning and memory of the animals. Extent of oxidative stress was measured by estimating the levels of brain glutathione (GSH) and thiobarbituric acid reactive species (TBARS). Brain acetylcholinestrase (AChE) activity was also estimated. The brain activity of myeloperoxidase (MPO) was measured as a marker of inflammation. STZ and ageing results in marked decline in MWM performance of the animals, reflecting impairment of learning and memory. STZ treated mice and aged mice exhibited a marked accentuation of AChE activity, TBARS and MPO activity along with fall in GSH level. Further the stained micrographs of STZ treated mice and aged mice indicate pathological changes, severe neutrophilic infiltration and amyloid deposition. Rolipram treatment significantly attenuated STZ induced and age related memory deficits, biochemical and histopathological alterations. The findings demonstrate the potential of Rolipram in memory dysfunctions which may probably be attributed to its anti-cholinesterase, anti-amyloid, anti-oxidative and anti-inflammatory effects. The study concludes that PDE-4 can be explored as a potential therapeutic target in dementia.
- Subjects :
- Male
0301 basic medicine
Aging
medicine.medical_specialty
Morris water navigation task
Plaque, Amyloid
medicine.disease_cause
Antioxidants
Streptozocin
Mice
03 medical and health sciences
0302 clinical medicine
Piperidines
Alzheimer Disease
Internal medicine
medicine
TBARS
Animals
Learning
Donepezil
Maze Learning
Neuroinflammation
Rolipram
Inflammation
Pharmacology
Memory Disorders
biology
business.industry
Brain
General Medicine
Streptozotocin
Oxidative Stress
030104 developmental biology
Endocrinology
Neutrophil Infiltration
Ageing
Myeloperoxidase
Indans
Acetylcholinesterase
biology.protein
Female
Cholinesterase Inhibitors
Phosphodiesterase 4 Inhibitors
business
030217 neurology & neurosurgery
Oxidative stress
medicine.drug
Subjects
Details
- ISSN :
- 07533322
- Volume :
- 88
- Database :
- OpenAIRE
- Journal :
- Biomedicine & Pharmacotherapy
- Accession number :
- edsair.doi.dedup.....c58033468820cb2c8a7593c986626e06