Curcumin ameliorates impaired insulin/IGF signalling and memory deficit in a streptozotocin-treated rat model

Abstract

Increased serum insulin levels and reduced peripheral insulin activities seen in insulin resistance syndrome are associated with age-dependent cognitive impairment and Sporadic Alzheimer's Disease (SAD), suggesting a disturbance in the insulin signalling system in the brain and possibly being one of the causes of dementia. Therefore, the streptozotocin (STZ)-induced animal may be an appropriate model for the investigation of SAD and related dementia. This study was designed to investigate the beneficial effect of Curcumin (CUR), a neuroprotective agent, on intracerebroventricular (ICV) STZ-induced cognitive impairment in rats. For this purpose, adult male Wistar rats were bilaterally ICV injected with STZ (3 mg/kg). An artificial cerebrospinal fluid (aCSF) was given to the control group (SHAM) instead of STZ on days 1 and 3. Learning and memory performance were assessed using the "passive avoidance task" and the "Morris water maze test". After confirmation of acquisition impairment with these tests, the STZ group was divided into two subgroups: STZ+ vehicle (Vh) and STZ+CUR. The rats in the SHAM and STZ+Vh groups were administered intraperitoneally with 0.5 ml Vh and the rats in the STZ+CUR group were treated intraperitoneally with CUR (300 mg kg −1 day −1 in Vh) for 10 days starting from the 25th day after STZ injection. The Morris water maze test was reapplied on the 35th day after STZ injection and all of the rats were sacrificed on day 36 for quantitation of IGF-1 and for histopathological evaluation. Rats in the STZ+CUR group were found to have a higher performance in cognitive tests than rats in the STZ+Vh group (P<0.01). In parallel with the cognitive tests, IGF-1 levels were decreased in all of the STZ-injected groups (1.78±0.34) compared to the SHAM group (3.46±0.41). In contrast, CUR treatment significantly increased IGF-1 levels (P<0.001). The degree of neuronal loss decreased after CUR treatment compared to the SHAM group (P< 0.02). These results clearly indicate that CUR treatment is effective in reducing the cognitive impairment caused AGE

What have we learned from the streptozotocin-induced animal model of sporadic Alzheimer’s disease, about the therapeutic strategies in Alzheimer’s research

“…In another experiment, treatment with curcumin (300 mg/kg i.p. for 10 days) initiated from the 25th day after STZicv injection led to cognitive improvement associated with restoration of the STZ-icv induced decrement in insulin growth factor (IGF)-1 in the brain as well as to the reduced neuronal loss (Isik et al 2009). Furthermore, the noted beneficial effect of curcumin (20 mg/kg per os for 14 days) on STZinduced dementia in mice was significantly abolished by pre-treatment with PPAR-gamma receptor antagonist bisphenol-A-diglycidyl ether, i.e., BADGE (30 mg/kg i.p.…”

Insulin-like growth factors are more effective than progastrin in reversing proapoptotic effects of curcumin: critical role of p38MAPK

“…However, anticancer effects of curcumin, independent of IGF-I-R inhibition, have also been reported (2). At the same time, an increase in IGF-I levels has been reported in response to curcumin in diabetic rats (14). Thus inhibitory vs. stimulatory effects of curcumin on IGF system may be specific to the cell or system.…”

The Effect of Apocynin on Motor and Cognitive Functions in Experimental Alzheimer’s disease

“…The technique of ventricular cannulation has been reported elsewhere (21). Briefly, the heads were stabilized on the stereotaxic frame (ASI instruments, Istanbul) 5 mm above the incisor bar interaural line.…”

“…The experimental group received totally 3mg/kg STZ and the control group received 20 μl of artificial cerebrospinal fluid (CSF) (Sigma) via Hamiltonian syringe (Picture 1C). The time required to induce neurodegenerative changes was set for 21 days (21,23).…”

“…In recent years, the application of protective agents to reduce the effects of endogenous oxidative stress and metabolic events related to external factors has been widespread (2,3,16,17,18,21,26,27,28). It assumes that microglia reaction against amyloid plaques with subsequent release of reactive oxygen species is the major damaging factor (20,29).…”