Long-term effects of intracranial islet grafting on cognitive functioning in a rat metabolic model of sporadic Alzheimer's disease-like dementia.

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  • Additional Information
    • Source:
      Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE
    • Publication Information:
      Original Publication: San Francisco, CA : Public Library of Science
    • Subject Terms:
      Alzheimer Disease/*therapy ; Cognition Disorders/*therapy ; Insulin/*biosynthesis ; Islets of Langerhans Transplantation/*methods; Alzheimer Disease/metabolism ; Alzheimer Disease/pathology ; Animals ; Brain/metabolism ; Brain/pathology ; Brain/surgery ; Cognition/physiology ; Cognition Disorders/metabolism ; Cognition Disorders/pathology ; Disease Models, Animal ; Hippocampus/metabolism ; Hippocampus/pathology ; Hippocampus/surgery ; Humans ; Islets of Langerhans/metabolism ; Maze Learning ; Memory/physiology ; Rats
    • Abstract:
      Accumulating evidence suggests that Alzheimer's disease is associated with brain insulin resistance, as are some other types of dementia. Intranasal insulin administration has been suggested as a potential approach to overcoming brain insulin resistance and improving cognitive functions. Islet transplantation into the cranial subarachnoid cavity was used as an alternative route for insulin delivery into the brain. Recently, the authors showed the short-term beneficial cognitive effect of a small number of intracranially grafted islets in rats with cognitive dysfunction induced by intracerebroventricular administration of streptozotocin (icv-STZ). This was associated with continuous and safe insulin delivery to the rat brain. The current study investigated the long-term effect of intracranial grafting of islets on cognitive functioning in icv-STZ rats. Severe dementia, associated with obesity and cerebral amyloid-β angiopathy, was induced in Lewis inbred rats by icv-STZ. Two months after icv-STZ, one hundred syngeneic islets were transplanted into the cranial subarachnoid space. Two and six months later, cognitive alterations were assessed by Morris water-maze tests. Islet graft survival was evaluated by immunohistochemical and biochemical assays. Improvement was found in spatial learning and memory of grafted rats as opposed to the sham-operated icv-STZ rats. The grafted islets showed intact morphology, intensive expression of insulin, glucagon and glucose transporter 2. Normoglycemic obesity and cerebral amyloid-β angiopathy were found in both grafted and sham-operated icv-STZ rats. In conclusion, islet grafting into cranial subarachnoid space provides an efficient and safe approach for insulin delivery to the brain, leading to a long-term attenuation of icv-STZ-induced cognitive dysfunction.
      Competing Interests: The authors have declared that no competing interests exist.
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    • Accession Number:
      0 (Insulin)
    • Publication Date:
      Date Created: 20200114 Date Completed: 20200416 Latest Revision: 20200416
    • Publication Date:
      20240105
    • Accession Number:
      PMC6957181
    • Accession Number:
      10.1371/journal.pone.0227879
    • Accession Number:
      31929603