Chromium picolinate attenuates cognitive deficit in ICV-STZ rat paradigm of sporadic Alzheimer's-like dementia via targeting neuroinflammatory and IRS-1/PI3K/AKT/GSK-3β pathway.

Authors:
Mr. Ansab Akhtar, B.Pharmacy, M.S
Mr. Ansab Akhtar, B.Pharmacy, M.S
Division of Pharmacology, UIPS, Panjab University
Ph.D research scholar
Cognitive neuroscience, Preclinical studies, Behavioral pharmacology, Molecular pharmacology
Chandigarh, Punjab | India

Inflammopharmacology 2020 Apr 3;28(2):385-400. Epub 2020 Jan 3.

Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, 160014, India.

Alzheimer's disease (AD) is prevalent in old age people and is one of the most common brain diseases. Brain insulin resistance, neuroinflammation, oxidative stress, and mitochondrial and cholinergic dysfunction are key features of the disease. In our study, streptozotocin (STZ) in a dose of 3 mg/kg was injected in male Wistar rats bilaterally through the intracerebroventricular (ICV) route on stereotaxic apparatus. Chromium picolinate (CrPic) was tested at doses of 1 mg/kg, 2 mg/kg, and 4 mg/kg, while rivastigmine (2 mg/kg) was used as reference standard drug. Cognitive dysfunction induced by STZ was assessed by behavioral tests like Morris water maze and novel object recognition test. Treatment with CrPic revealed attenuation of cognitive deficit. This was confirmed by behavioral tests, biochemical estimations of antioxidant enzymes, oxidative stress, nitrosative stress, and cholinergic and mitochondrial activity. CrPic did not change AchE activity significantly. STZ-induced neuroinflammation evident by increased TNF-α, IL-6, and CRP levels was also significantly decreased by CrPic. Dysfunctional insulin signaling after ICV-STZ was demonstrated by reduced IRS-1, PI3K, AKT, BDNF gene expression, and increased GSK-3β, NF-κB gene expression with the help of qRT-PCR. CrPic treatment produced an improvement in insulin signaling revealed by increased gene expression of IRS-1, PI3-K, AKT, BDNF, and decreased gene expression of GSK-3β and NF-κB. It was concluded that CrPic reversed AD pathology revealed by improved memory, reduced oxidative stress, neuroinflammation, mitochondrial dysfunction, and upregulated insulin signaling.

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10787-019-00681-7DOI Listing
April 2020

Publication Analysis

Top Keywords

gene expression
16
oxidative stress
12
insulin signaling
12
behavioral tests
8
akt bdnf
8
cognitive deficit
8
chromium picolinate
8
crpic
6
nitrosative stress
4
stress cholinergic
4
stress nitrosative
4
biochemical estimations
4
estimations antioxidant
4
antioxidant enzymes
4
enzymes oxidative
4
tests biochemical
4
activity crpic
4
neuroinflammation evident
4
stz-induced neuroinflammation
4
evident increased
4

References

(Supplied by CrossRef)

RA Anderson et al.
J Trace Elem Exp Med 1996

RA Anderson et al.
J Am Coll Nutr 2001

M Antunes et al.
Cogn Process 2012

L Baki et al.
EMBO J 2004

SB Berman et al.
J Neurochem 1999

R Biasibetti et al.
Behav Brain Res 2013

RS Bitner et al.
J Neurosci 2007

A Claiborne et al.
1985

G Colombo et al.
J Chromatogr B 2016

SM de la Monte et al.
Curr Alzheimer Res 2012

J Pino Del et al.
Arch Toxicol 2016

Similar Publications