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


Autoři: Konstantin Bloch aff001;  Shay Henry Hornfeld aff002;  Shira Dar aff002;  Alexey Vanichkin aff003;  Irit Gil-Ad aff002;  Pnina Vardi aff001;  Abraham Weizman aff002
Působiště autorů: Laboratory of Diabetes and Obesity Research, Felsenstein Medical Research Center, Sackler Faculty of Medicine, Tel Aviv University, Petah Tikva, Israel aff001;  Laboratory of Biological Psychiatry, Felsenstein Medical Research Center, Sackler Faculty of Medicine, Tel Aviv University, Petah Tikva, Israel aff002;  Laboratory of Transplantation, Felsenstein Medical Research Center, Sackler Faculty of Medicine, Tel Aviv University, Petah Tikva, Israel aff003;  Research Unit, Geha Mental Health Center, Petah Tikva, Israel aff004
Vyšlo v časopise: PLoS ONE 15(1)
Kategorie: Research Article
doi: 10.1371/journal.pone.0227879

Souhrn

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.

Klíčová slova:

Alzheimer's disease – Animal cognition – Body weight – Cerebrospinal fluid – Cognitive impairment – Enzyme-linked immunoassays – Insulin – Obesity


Zdroje

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2020 Číslo 1