title: Calcineurin inhibitors improve memory loss and neuropathological changes in mouse model of dementia.
abstract: The present study was designed to investigate the potential of Cyclosporine (CsA) and Tacrolimus, the inhibitors of calcineurin (CaN) in cognitive deficits of mice.
  
  
  
  Streptozotocin [STZ, 3mg/kg, injected intracerebroventricular (i.c.v.)] was used to induce memory deficits in NIH mice, while aged mice separately taken served as a natural model of dementia. Morris water maze (MWM) test was employed to evaluate learning and memory of the animals. A battery of biochemical and histopathological studies was also performed. 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 estimated to assess cholinergic activity. The brain level of myeloperoxidase (MPO) was measured as a marker of inflammation.
  
  
  
  STZ i.c.v. and aging results in marked decline in MWM performance of the animals, reflecting impairment of learning and memory. STZ i.c.v. treated mice and aged mice exhibited a marked accentuation of AChE activity, TBARS and MPO levels along with a fall in GSH level. Further the stained micrographs of STZ treated mice and aged mice indicate pathological changes, severe neutrophilic infiltration and amyloid deposition. Cyclosporine and Tacrolimus treatment significantly attenuated STZ induced and age related memory deficits, biochemical and histopathological alterations.
  
  
  
  The findings demonstrate the potential of CaN inhibitors Cyclosporine and Tacrolimus in memory dysfunctions which may probably be attributed to anti-cholinesterase, anti-amyloid, anti-oxidative and anti-inflammatory effects. It is concluded that CaN can be explored as a potential therapeutic target in dementia.
authors.affiliation: 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.
authors.forename: Amit
authors.initials: A
authors.lastname: Kumar
authors.affiliation: Pharmacology Division, Department of Pharmaceutical Sciences and Drug Research, Faculty of Medicine, Punjabi university, Patiala 147002, Punjab, India. Electronic address: nirmal_puru@rediffmail.com.
authors.forename: Nirmal
authors.initials: N
authors.lastname: Singh
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D065095:Calcineurin Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D003704:Dementia / Q000188:drug therapy* / Q000473:pathology / Q000523:psychology; D005260:Female; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects*; D051379:Mice; D013311:Streptozocin / Q000494:pharmacology
chemical_list: D065095:Calcineurin Inhibitors; D013311:Streptozocin
keywords: Age; Calcineurin; Cyclosporine; Dementia; STZ; Tacrolimus