Vol.:(0123456789) 1 3 Infammopharmacology https://doi.org/10.1007/s10787-019-00681-7 ORIGINAL ARTICLE Chromium picolinate attenuates cognitive defcit in ICV‑STZ rat paradigm of sporadic Alzheimer’s‑like dementia via targeting neuroinfammatory and IRS‑1/PI3K/AKT/GSK‑3β pathway Ansab Akhtar 1  · Jatinder Dhaliwal 1  · Priyanka Saroj 1  · Ankit Uniyal 1  · Mahendra Bishnoi 2  · Sangeeta Pilkhwal Sah 1 Received: 31 October 2019 / Accepted: 16 December 2019 © Springer Nature Switzerland AG 2020 Abstract Alzheimer’s disease (AD) is prevalent in old age people and is one of the most common brain diseases. Brain insulin resist- ance, neuroinfammation, 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 intracer- ebroventricular (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 attenu- ation of cognitive defcit. This was confrmed by behavioral tests, biochemical estimations of antioxidant enzymes, oxidative stress, nitrosative stress, and cholinergic and mitochondrial activity. CrPic did not change AchE activity signifcantly. STZ- induced neuroinfammation evident by increased TNF-α, IL-6, and CRP levels was also signifcantly 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, neuroinfammation, mitochondrial dysfunction, and upregulated insulin signaling. Keywords ICV-STZ · Chromium picolinate · Oxidative stress · Neuroinfammation · Insulin resistance · Alzheimer’s disease Introduction Alzheimer’s disease (AD) is one of the most common forms of dementia afecting elderly people. People sufering from AD show symptoms of cognitive impairment, memory def- icit, and disturbances in behavioral activities (Onor et al. 2006). According to the 2017 report, around 44 million peo- ple globally are sufering from AD with disease prevalence likely to rise to 115 million by 2050 (Sargent and Brown 2017). Despite more than 30 years of intense investigation, the feld lacks consensus regarding the etiology and pathogen- esis of sporadic AD, and therefore, we still do not know the best strategies for treating and preventing this debilitat- ing disease. Moreover, the prevalence of AD is increasing rapidly in the absence of truly efective therapies. Epide- miologic studies in elderly, experimental investigations in humans and animal models consistently demonstrate that Inflammopharmacology * Sangeeta Pilkhwal Sah spilkhwal@redifmail.com Ansab Akhtar ansabakhtar@gmail.com Jatinder Dhaliwal jatinderdhaliwal57@yahoo.com Priyanka Saroj priyanka1960@gmail.com Ankit Uniyal ankituniyal1994rsb@gmail.com Mahendra Bishnoi mbishnoi@gmail.com 1 Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160014, India 2 National Agri-Food Biotechnology Institute (NABI), Sector-81, SAS Nagar, Mohali, Punjab 140306, India