Limits...
Long-term treatment with intranasal insulin ameliorates cognitive impairment, tau hyperphosphorylation, and microglial activation in a streptozotocin-induced Alzheimer ’ s rat model

View Article: PubMed Central - PubMed

ABSTRACT

Recent evidence reveals that aberrant brain insulin signaling plays an important role in the pathology of Alzheimer’s disease (AD). Intranasal insulin administration has been reported to improve memory and attention in healthy participants and in AD patients. However, the underlying molecular mechanisms are poorly understood. Here, we treated intracerebroventricular streptozotocin-injected (ICV-STZ) rats, a commonly used animal model of sporadic AD, with daily intranasal delivery of insulin (2 U/day) for 6 consecutive weeks and then studied their cognitive function with the Morris water maze test and biochemical changes via Western blotting. We observed cognitive deficits, tau hyperphosphorylation, and neuroinflammation in the brains of ICV-STZ rats. Intranasal insulin treatment for 6 weeks significantly improved cognitive function, attenuated the level of tau hyperphosphorylation, ameliorated microglial activation, and enhanced neurogenesis in ICV-STZ rats. Additionally, our results indicate that intranasal delivery of insulin probably attenuates tau hyperphosphorylation through the down-regulation of ERK1/2 and CaMKII in the brains of ICV-STZ rats. Our findings demonstrate a beneficial effect of intranasal insulin and provide the mechanistic basis for treating AD patients with intranasal insulin.

No MeSH data available.


Effect of intranasal insulin on the levels of doublecortin and synaptic proteins.Hippocampus extracts were measured via Western blots (a,c) and quantitative analysis was normalized to the GAPDH level (b,d). Data are expressed as the means ± SEM (n = 9–11 per group). *P < 0.05 versus the control group; #P < 0.05 versus the STZ/Sal group.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC5382700&req=5

f5: Effect of intranasal insulin on the levels of doublecortin and synaptic proteins.Hippocampus extracts were measured via Western blots (a,c) and quantitative analysis was normalized to the GAPDH level (b,d). Data are expressed as the means ± SEM (n = 9–11 per group). *P < 0.05 versus the control group; #P < 0.05 versus the STZ/Sal group.

Mentions: To evaluate the effects of insulin on neurogenesis, the levels of doublecortin (DCX), a marker of newborn neurons, were evaluated in the hippocampal homogenates of these rats. We did not observe a significant difference in the level of DCX in the hippocampus of ICV-STZ rats compared to control rats. However, intranasal insulin treatment dramatically upregulated the level of DCX in ICV-STZ rats compared to control rats (Fig. 5a,b), indicating that intranasal insulin might promote neurogenesis.


Long-term treatment with intranasal insulin ameliorates cognitive impairment, tau hyperphosphorylation, and microglial activation in a streptozotocin-induced Alzheimer ’ s rat model
Effect of intranasal insulin on the levels of doublecortin and synaptic proteins.Hippocampus extracts were measured via Western blots (a,c) and quantitative analysis was normalized to the GAPDH level (b,d). Data are expressed as the means ± SEM (n = 9–11 per group). *P < 0.05 versus the control group; #P < 0.05 versus the STZ/Sal group.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5382700&req=5

f5: Effect of intranasal insulin on the levels of doublecortin and synaptic proteins.Hippocampus extracts were measured via Western blots (a,c) and quantitative analysis was normalized to the GAPDH level (b,d). Data are expressed as the means ± SEM (n = 9–11 per group). *P < 0.05 versus the control group; #P < 0.05 versus the STZ/Sal group.
Mentions: To evaluate the effects of insulin on neurogenesis, the levels of doublecortin (DCX), a marker of newborn neurons, were evaluated in the hippocampal homogenates of these rats. We did not observe a significant difference in the level of DCX in the hippocampus of ICV-STZ rats compared to control rats. However, intranasal insulin treatment dramatically upregulated the level of DCX in ICV-STZ rats compared to control rats (Fig. 5a,b), indicating that intranasal insulin might promote neurogenesis.

View Article: PubMed Central - PubMed

ABSTRACT

Recent evidence reveals that aberrant brain insulin signaling plays an important role in the pathology of Alzheimer&rsquo;s disease (AD). Intranasal insulin administration has been reported to improve memory and attention in healthy participants and in AD patients. However, the underlying molecular mechanisms are poorly understood. Here, we treated intracerebroventricular streptozotocin-injected (ICV-STZ) rats, a commonly used animal model of sporadic AD, with daily intranasal delivery of insulin (2&thinsp;U/day) for 6 consecutive weeks and then studied their cognitive function with the Morris water maze test and biochemical changes via Western blotting. We observed cognitive deficits, tau hyperphosphorylation, and neuroinflammation in the brains of ICV-STZ rats. Intranasal insulin treatment for 6 weeks significantly improved cognitive function, attenuated the level of tau hyperphosphorylation, ameliorated microglial activation, and enhanced neurogenesis in ICV-STZ rats. Additionally, our results indicate that intranasal delivery of insulin probably attenuates tau hyperphosphorylation through the down-regulation of ERK1/2 and CaMKII in the brains of ICV-STZ rats. Our findings demonstrate a beneficial effect of intranasal insulin and provide the mechanistic basis for treating AD patients with intranasal insulin.

No MeSH data available.