Impact of Single or Repeated Dose Intranasal Zinc-free Insulin in Young and Aged F344 Rats on Cognition, Signaling, and Brain Metabolism
| Autor: | Lawrence D. Brewer, Ai-Ling Lin, Nada M. Porter, Zana R. Majeed, Olivier Thibault, Shaniya Maimaiti, Hilaree N. Frazier, Katie L. Anderson, Vikas Bakshi |
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| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine Aging medicine.medical_specialty medicine.medical_treatment Blood–brain barrier 03 medical and health sciences Cognition 0302 clinical medicine Internal medicine Diabetes mellitus medicine Animals Insulin Cognitive decline Administration Intranasal biology business.industry Age Factors Brain medicine.disease Rats Inbred F344 Rats Zinc Insulin receptor 030104 developmental biology Endocrinology medicine.anatomical_structure Cerebral blood flow Nasal spray Cerebrovascular Circulation biology.protein Original Article Nasal administration Geriatrics and Gerontology business 030217 neurology & neurosurgery Signal Transduction |
| Zdroj: | The Journals of Gerontology Series A: Biological Sciences and Medical Sciences. 72:189-197 |
| ISSN: | 1758-535X 1079-5006 |
| DOI: | 10.1093/gerona/glw065 |
| Popis: | Novel therapies have turned to delivering compounds to the brain using nasal sprays, bypassing the blood brain barrier, and enriching treatment options for brain aging and/or Alzheimer's disease. We conducted a series of in vivo experiments to test the impact of intranasal Apidra, a zinc-free insulin formulation, on the brain of young and aged F344 rats. Both single acute and repeated daily doses were compared to test the hypothesis that insulin could improve memory recall in aged memory-deficient animals. We quantified insulin signaling in different brain regions and at different times following delivery. We measured cerebral blood flow (CBF) using MRI and also characterized several brain metabolite levels using MR spectroscopy. We show that neither acute nor chronic Apidra improved memory or recall in young or aged animals. Within 2 hours of a single dose, increased insulin signaling was seen in ventral areas of the aged brains only. Although chronic Apidra was able to offset reduced CBF with aging, it also caused significant reductions in markers of neuronal integrity. Our data suggest that this zinc-free insulin formulation may actually hasten cognitive decline with age when used chronically. |
| Databáze: | OpenAIRE |
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