JOURNAL ARTICLE

Protective effect of valproic acid in streptozotocin-induced sporadic Alzheimer's disease mouse model: possible involvement of the cholinergic system

Mirna Ezzat Sorial, Nesrine Salah El Dine El Sayed
Naunyn-Schmiedeberg's Archives of Pharmacology 2017, 390 (6): 581-593
28188358
Sporadic Alzheimer's disease (SAD) is a slowly progressive neurological disorder that is the most common form of dementia. Cholinergic system dysfunction and amyloid beta formation are the two main underlying pathological mechanisms for the disease development. In recent studies, insulin receptor desensitization and disturbances in the downstream effects of insulin receptor signaling were observed in the brains of Alzheimer's patients. Currently, intracereberoventricular (ICV) injection of streptozotocin (STZ) is found to induce behavioral, neurochemical, and structural alterations in animals resembling those found in SAD patients. Valproic acid (VPA), a histone deacetylase inhibitor (HDACi), was recently shown to regulate the transcription of several genes in both in vivo and in vitro models of Alzheimer's disease. The aim of the current study is to investigate the potential effect of different doses of valproic acid, in an ICV-STZ-induced animal model of SAD. Streptozotocin-injected mice showed cognitive and spatial memory dysfunction in the Y-maze, object recognition test, and Morris water maze (MWM) neurobehavioral tests. The mice also exhibited a decrease in acetylcholine (ACh) and neprilysin (NEP) levels accompanied by an increase in acetylcholinesterase (AChE) activity. For the first time to our knowledge, our findings have shown that VPA is capable of restoring ACh levels in ICV-STZ-injected mice, as well as normalizing both NEP levels and AChE activity. Via this mechanism, an enhancement of cognitive functions is observed. Thus, VPA is suggested to be a promising therapeutic approach against SAD.

Full Text Links

Find Full Text Links for this Article

Discussion

You are not logged in. Sign Up or Log In to join the discussion.

Trending Papers

Remove bar
Read by QxMD icon Read
28188358
×

Save your favorite articles in one place with a free QxMD account.

×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"