Inhibitor of Phosphodiestearse-4 improves memory deficits, oxidative stress, neuroinflammation and neuropathological alterations in mouse models of dementia of Alzheimer's Type.
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.
CNS and CVS research lab., Pharmacology division, Department of Pharmaceutical Sciences and Drug Research, Faculty of Medicine, Punjabi university, Patiala- 147002, Punjab, India. Electronic address: amit2050@yahoo.co.in.
Amit
A
Kumar
Pharmacology division, Department of Pharmaceutical Sciences and Drug Research, Faculty of Medicine, Punjabi university, Patiala- 147002, Punjab, India. Electronic address: nirmal_puru@rediffmail.com.
Nirmal
N
Singh
D000110:Acetylcholinesterase / Q000378:metabolism; D000375:Aging / Q000187:drug effects; D000544:Alzheimer Disease / Q000139:chemically induced / Q000188:drug therapy* / Q000523:psychology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use; D000077265:Donepezil; D005260:Female; D007189:Indans / Q000627:therapeutic use; D007249:Inflammation / Q000139:chemically induced / Q000517:prevention & control; D007858:Learning / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000139:chemically induced / Q000517:prevention & control* / Q000523:psychology; D051379:Mice; D020556:Neutrophil Infiltration / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D058988:Phosphodiesterase 4 Inhibitors / Q000627:therapeutic use*; D010880:Piperidines / Q000627:therapeutic use; D058225:Plaque, Amyloid / Q000517:prevention & control; D020889:Rolipram / Q000627:therapeutic use*; D013311:Streptozocin
D000975:Antioxidants; D002800:Cholinesterase Inhibitors; D007189:Indans; D058988:Phosphodiesterase 4 Inhibitors; D010880:Piperidines; D013311:Streptozocin; D000077265:Donepezil; D000110:Acetylcholinesterase; D020889:Rolipram
Age; Dementia; Morris water maze; Phosphodiesterases; Rolipram