Calcineurin Inhibition and Protein Kinase A Activation Limits Cognitive Dysfunction and Histopathological Damage in a Model of Dementia of the Alzheimer’s Type

Title:Calcineurin Inhibition and Protein Kinase A Activation Limits Cognitive Dysfunction and Histopathological Damage in a Model of Dementia of the Alzheimer’s Type

Volume: 15 Issue: 3

Author(s): Amit Kumar and Nirmal Singh*

Affiliation:

• Pharmacology Division, Department of Pharmaceutical Sciences and Drug Research, Faculty of Medicine, Punjabi University, Patiala-147002, Punjab,India

Keywords: Dementia, STZ, Age, Tacrolimus, Forskolin, Protein Kinase A.

Abstract: Aim: The aim of the present work was to explore the outcome of combination of Calcineurin (CaN) inhibitor and Protein Kinase A (PKA) activator, in mouse models of experimental dementia.

Methods: Cognitive deficits were induced in mice by injecting Streptozotocin (STZ) intracerebroventricularly (i.c.v.); on the other hand aged animals were procured as a natural model of dementia. To assess cognitive function of mice Morris water maze (MWM) test was utilized; various biochemical studies and histopathological studies were also carried out.

Results: STZ injection and aging resulted in significant development of cognitive deficits; along-with enhancement of Myeloperoxidase (MPO) levels, Thiobarbituric Acid Reactive Species (TBARS), Acetylcholinestrase (AChE) activity, and reduced Glutathione (GSH) levels. Histopathological studies demonstrated pathological changes such as amyloid deposition and severe neutrophilic infiltration in brains of these mice. Donepezil /combination of Tacrolimus and Forskolin treatment markedly improve cognitive function, biochemical parameters, and histopathological alterations in STZ treated and aged mice.

Conclusion: The outcome reveals that combination of CaN inhibitor and PKA activator has significantly alleviated memory dysfunction, biochemical alteration and histopathological changes quiet comparable to Donepezil. It has been inferred that combination of CaN and PKA can be served as an important target in dementia.

Cite this article as:

Kumar Amit and Singh Nirmal*, Calcineurin Inhibition and Protein Kinase A Activation Limits Cognitive Dysfunction and Histopathological Damage in a Model of Dementia of the Alzheimer’s Type, Current Neurovascular Research 2018; 15 (3) . https://dx.doi.org/10.2174/1567202615666180813125125