title: Intracranial pancreatic islet transplantation increases islet hormone expression in the rat brain and attenuates behavioral dysfunctions induced by MK-801 (dizocilpine).
abstract: The treatment of rodents with non-competitive antagonist of the N-Methyl-D-aspartate (NMDA) receptor, MK-801 (dizocilpine), induces symptoms of psychosis, deficits in spatial memory and impairment of synaptic plasticity. Recent studies have suggested that insulin administration might attenuate the cognitive dysfunctions through the modulatory effect on the expression of NMDA receptors and on the brain insulin signaling. Intrahepatic pancreatic islet transplantation is known as an efficient tool for correcting impaired insulin signaling. We examined the capacity of syngeneic islets grafted into the cranial subarachnoid cavity to attenuate behavioral dysfunctions in rats exposed to MK-801. Animals were examined in the open field (OF) and the Morris Water Maze (MWM) tests following acute or subchronic administration of MK-801. We found well-vascularized grafted islets expressing insulin, glucagon and somatostatin onto the olfactory bulb and prefrontal cortex. Significantly higher levels of insulin were detected in the hippocampus and prefrontal cortex of transplanted animals compared to the non-transplanted rats. All animals expressed normal peripheral glucose homeostasis for two months after transplantation. OF tests revealed that rats exposed to MK-801 treatment, showed hyper-responsiveness in motility parameters and augmented center field exploration compared to intact controls and these effects were attenuated by the grafted islets. Moreover, in the MWM, the rats treated with MK-801 showed impairment of spatial memory that were partially corrected by the grafted islets. In conclusion, intracranial islet transplantation leads to the expression of islet hormones in the brain and attenuates behavioral and cognitive dysfunctions in rats exposed to MK-801 administration without altering the peripheral glucose homeostasis.
authors.affiliation: Laboratory of Diabetes and Obesity Research, Felsenstein Medical Research Center, Sackler School of Medicine, Tel Aviv University, Petah Tikva, Israel. Electronic address: kbloch@post.tau.ac.il.
authors.forename: Konstantin
authors.initials: K
authors.lastname: Bloch
authors.affiliation: Laboratory of Biological Psychiatry, Felsenstein Medical Research Center, Sackler School of Medicine, Tel Aviv University, Petah Tikva, Israel.
authors.forename: Irit
authors.initials: I
authors.lastname: Gil-Ad
authors.affiliation: Laboratory of Biological Psychiatry, Felsenstein Medical Research Center, Sackler School of Medicine, Tel Aviv University, Petah Tikva, Israel.
authors.forename: Igor
authors.initials: I
authors.lastname: Tarasenko
authors.affiliation: Laboratory of Transplantation, Felsenstein Medical Research Center, Sackler School of Medicine, Tel Aviv University, Petah Tikva, Israel.
authors.forename: Alexey
authors.initials: A
authors.lastname: Vanichkin
authors.affiliation: Laboratory of Biological Psychiatry, Felsenstein Medical Research Center, Sackler School of Medicine, Tel Aviv University, Petah Tikva, Israel.
authors.forename: Michal
authors.initials: M
authors.lastname: Taler
authors.affiliation: Laboratory of Biological Psychiatry, Felsenstein Medical Research Center, Sackler School of Medicine, Tel Aviv University, Petah Tikva, Israel.
authors.forename: Shay Henry
authors.initials: SH
authors.lastname: Hornfeld
authors.affiliation: Laboratory of Diabetes and Obesity Research, Felsenstein Medical Research Center, Sackler School of Medicine, Tel Aviv University, Petah Tikva, Israel.
authors.forename: Pnina
authors.initials: P
authors.lastname: Vardi
authors.affiliation: Laboratory of Biological Psychiatry, Felsenstein Medical Research Center, Sackler School of Medicine, Tel Aviv University, Petah Tikva, Israel; Research Unit, Geha Mental Health Center, Petah Tikva, Israel.
authors.forename: Abraham
authors.initials: A
authors.lastname: Weizman
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000378:metabolism*; D002478:Cells, Cultured; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects; D007515:Islets of Langerhans / Q000378:metabolism*; D016381:Islets of Langerhans Transplantation; D008297:Male; D010187:Pancreatic Hormones / Q000378:metabolism*; D017397:Prefrontal Cortex / Q000187:drug effects; D051381:Rats; D011917:Rats, Inbred Lew; D016042:Transplantation, Heterotopic
chemical_list: D010187:Pancreatic Hormones; D016291:Dizocilpine Maleate
keywords: Behavioral dysfunctions; Brain insulin; Islet transplantation; MK-801 (dizocilpine); Peripheral glucose homeostasis; Subarachnoid space