The Role of Zinc Status on Spatial Memory, Hippocampal Synaptic Plasticity, and Insulin Signaling in icv-STZ-Induced Sporadic Alzheimer’s-Like Disease in Rats

Baltaci S. B., Unal O., Gulbahce-Mutlu E., Gumus H., Pehlivanoglu S., Yardimci A., ...More

Biological Trace Element Research, vol.200, no.9, pp.4068-4078, 2022 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 200 Issue: 9
  • Publication Date: 2022
  • Doi Number: 10.1007/s12011-021-02999-2
  • Journal Name: Biological Trace Element Research
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Aqualine, Aquatic Science & Fisheries Abstracts (ASFA), BIOSIS, CAB Abstracts, Chemical Abstracts Core, EMBASE, Food Science & Technology Abstracts, MEDLINE, Pollution Abstracts, Veterinary Science Database
  • Page Numbers: pp.4068-4078
  • Keywords: Alzheimer’s disease, Brain insulin resistance, Learning and memory, Neurodegeneration, Synaptic plasticity, Zinc
  • Istanbul Medipol University Affiliated: No


Alzheimer’s disease (AD), especially its sporadic form (sAD), is of multifactorial nature. Brain insulin resistance and disrupted zinc homeostasis are two key aspects of AD that remain to be elucidated. Here, we investigated the effects of dietary zinc deficiency and supplementation on memory, hippocampal synaptic plasticity, and insulin signaling in intracerebroventricular streptozotocin (icv-STZ)-induced sAD in rats. The memory performance was evaluated by Morris water maze. The expression of hippocampal protein and mRNA levels of targets related to synaptic plasticity and insulin pathway was assessed by Western blot and real-time quantitative PCR. We found memory deficits in icv-STZ rats, which were fully recovered by zinc supplementation. Western blot analysis revealed that icv-STZ treatment significantly reduced hippocampal PSD95 and p-GSK3β, and zinc supplementation restored the normal protein levels. mRNA levels of BDNF, PSD95, SIRT1, GLUT4, insulin receptor, and ZnT3 were found to be reduced by icv-STZ and reestablished by zinc supplementation. Our data suggest that zinc supplementation improves cognitive deficits and rescues the decline in key molecular targets of synaptic plasticity and insulin signaling in hippocampus caused by icv-STZ induced sAD in rats.