Central Nervous System Delivery of Intranasal Insulin: Mechanisms of Uptake and Effects on Cognition

Journal of Alzheimer's Disease

Volumn 47, Issue 3, 2015, Pages 715-728

  Salameh, Therese S ^a,b   Bullock, Kristin M ^a   Hujoel, Isabel A ^a   Niehoff, Michael L ^c,d   Wolden Hanson, Tami ^a   Kim, Junghyun ^c   Morley, John E ^c   Farr, Susan A ^c,d   Banks, William A ^a,b  

^a VA PUGET SOUND HEALTH CARE SYSTEM   (United States)

^b UNIVERSITY OF WASHINGTON SCHOOL OF MEDICINE   (United States)

^c SAINT LOUIS UNIVERSITY SCHOOL OF MEDICINE   (United States)

^d VETERANS AFFAIRS MEDICAL CENTER   (United States)

Author keywords

Alzheimer's disease; cognition; insulin; intranasal administration

Indexed keywords

PROTEIN KINASE C; RECOMBINANT HUMAN INSULIN; ANTIDIABETIC AGENT; INSULIN; NOOTROPIC AGENT; RADIOACTIVE IODINE; RECOMBINANT PROTEIN;

ALZHEIMER DISEASE; AMNESIA; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BLOOD BRAIN BARRIER; CENTRAL NERVOUS SYSTEM; COGNITION; CONTROLLED STUDY; DRUG DELIVERY SYSTEM; DRUG EFFECT; DRUG EFFICACY; DRUG UPTAKE; ENZYME INHIBITION; LEARNING; MALE; MOUSE; NONHUMAN; PRIORITY JOURNAL; ANIMAL; ANTAGONISTS AND INHIBITORS; BRAIN; DRUG EFFECTS; HUMAN; INTRANASAL DRUG ADMINISTRATION; MAZE TEST; METABOLISM; PRECLINICAL STUDY; RECOGNITION;

ADMINISTRATION, INTRANASAL; ANIMALS; BRAIN; COGNITION; DRUG EVALUATION, PRECLINICAL; HUMANS; HYPOGLYCEMIC AGENTS; INSULIN; IODINE RADIOISOTOPES; MALE; MAZE LEARNING; MICE; NOOTROPIC AGENTS; PROTEIN KINASE C; RECOGNITION (PSYCHOLOGY); RECOMBINANT PROTEINS;

EID: 84938691342     PISSN: 13872877     EISSN: 18758908     Source Type: Journal    
DOI: 10.3233/JAD-150307     Document Type: Article

References (44)

1. Hölscher C, Li L (2010) New roles for insulin-like hormones in neuronal signalling and protection: New hopes for novel treatments of Alzheimers disease? Neurobiol Aging 31, 1495-1502.
2. de la Monte SM, Tong M (2014) Brain metabolic dysfunction at the core of Alzheimers disease. Biochem Pharmacol 88, 548-559.
3. Rivera EJ, Goldin A, Fulmer N, Tavares R, Wands JR, de la Monte SM (2005) Insulin and insulin-like growth factor expression and function deteriorate with progression of Alzheimers disease: Link to brain reductions in acetylcholine. J Alzheimers Dis 8, 247-268.
4. Talbot K, Wang H-Y, Kazi H, Han L-Y, Bakshi KP, Stucky A, Fuino RL, Kawaguchi KR, Samoyedny AJ, Wilson RS, Arvanitakis Z, Schneider JA, Wolf BA, Bennett DA, Trojanowski JQ, Arnold SE (2012) Demonstrated brain insulin resistance in Alzheimers disease patients is associated with IGF-1 resistance, IRS-1 dysregulation, and cognitive decline. J Clin Invest 122, 1316-1338.
5. Steen E, Terry BM, Rivera EJ, Cannon JL, Neely TR, Tavares R, Xu XJ, Wands JR, de la Monte SM (2005) Impaired insulin and insulin-like growth factor expression and signaling mechanisms in Alzheimers disease -is this type 3 diabetes? J Alzheimers Dis 7, 63-80.
6. Plum L, Schubert M, Brüning JC (2005) The role of insulin receptor signaling in the brain. Trends Endocrinol Metab 16, 59-65.
7. Abbott M-A, Wells DG, Fallon JR (1999) The insulin receptor tyrosine kinase substrate p58/53 and the insulin receptor are components of CNS synapses. J Neurosci 19, 7300-7308.
8. McNay EC, Ong CT, McCrimmon RJ, Cresswell J, Bogan JS, Sherwin RS (2010) Hippocampal memory processes are modulated by insulin and high-fat-induced insulin resistance. Neurobiol Learn Mem 93, 546-553.
9. Benedict C, Hallschmid M, Hatke A, Schultes B, Fehm HL, Born J, Kern W (2004) Intranasal insulin improves memory in humans. Psychoneuroendocrinology 29, 1326-1334.
10. Kern W, Peters A, Fruehwald-Schultes B, Deininger E, Born J, Fehm HL (2001) Improving influence of insulin on cognitive functions in humans. Neuroendocrinology 74, 270-280.
11. Chen Y, Run X, Liang Z, Zhao Y, Dai C-l, Iqbal K, Liu F, Gong C-X (2014) Intranasal insulin prevents anesthesiainduced hyperphosphorylation of tau in 3xTg-AD mice. Front Aging Neurosci 6, 100.
12. Dong Y, Wu X, Xu Z, Zhang Y, Xie Z (2012) Anesthetic isoflurane increases phosphorylated tau levels mediated by caspase activation and Aβ generation. PLoS OneE 7, e39386.
13. Shen X, Dong Y, Xu Z, Wang H, Miao C, Soriano SG, Sun D, Baxter MG, Zhang Y, Xie Z (2013) Selective anesthesiainduced neuroinflammation in developing mouse brain and cognitive impairment. Anesthesiology 118, 502-515.
14. Bianchi SL, Tran T, Liu C, Lin S, Li Y, Keller JM, Eckenhoff RG, Eckenhoff MF (2008) Brain and behavior changes in 12-month-old Tg2576 and nontransgenic mice exposed to anesthetics. Neurobiol Aging 29, 1002-1010.
15. Craft S, Baker LD, Montine TJ, Minoshima S, Watson GS, Claxton A, Arbuckle M, Callaghan M, Tsai E, Plymate SR, Green PS, Leverenz J, Cross D, Gerton B (2012) Intranasal insulin therapy for Alzheimer disease and amnestic mild cognitive impairment:Apilot clinical trial. Arch Neurol 69, 29-38.
16. Reger MA, Watson GS, Frey Ii WH, Baker LD, Cholerton B, Keeling ML, Belongia DA, Fishel MA, Plymate SR, Schellenberg GD, Cherrier MM, Craft S (2006) Effects of intranasal insulin on cognition in memory-impaired older adults: Modulation by APOE genotype. Neurobiol Aging 27, 451-458.
17. Claxton A, Baker LD, Wilkinson CW, Trittschuh EH, Chapman D, Watson GS, Cholerton B, Plymate SR, Arbuckle M, Craft S (2013) Sex and ApoE genotype differences in treatment response to two doses of intranasal insulin in adults with mild cognitive impairment or Alzheimers disease. J Alzheimers Dis 35, 789-797.
18. Rosenbloom M, Barclay T, Pyle M, Owens B, Cagan A, Anderson C, Frey W, II, Hanson L (2014) A single-dose pilot trial of intranasal rapid-Acting insulin in apolipoprotein E4 carriers with mild-moderate Alzheimers disease. CNS Drugs 28, 1185-1189.
19. Lochhead JJ, Thorne RG (2012) Intranasal delivery of biologics to the central nervous system. Adv Drug Deliv Rev 64, 614-628.
20. Lochhead JJ, Wolak DJ, Pizzo ME, Thorne RG (2015) Rapid transport within cerebral perivascular spaces underlies widespread tracer distribution in the brain after intranasal administration. J Cereb Blood Flow Metab 35, 371-381.
21. Greenwood FC, Hunter WM (1963) The preparation of 131Ilabelled human growth hormone of high specific radioactivity. Biochem J 89, 114-123.
22. Glowinski J, Iversen L (1966) Regional studies of catecholamines in the rat brain. I.Tthe disposition of[3H]norepinephrine, [3H]dopamine and [3H]dopa in various regions of the brain. J Neurochem 13, 655-659.
23. Nonaka N, Farr SA, Nakamachi T, Morley JE, Nakamura M, Shioda S, Banks WA (2012) Intranasal administration of PACAP: Uptake by brain and regional brain targeting with cyclodextrins. Peptides 36, 168-175.
24. Fiorini A, Sultana R, Förster S, Perluigi M, Cenini G, Cini C, Cai J, Klein JB, Farr SA, Niehoff ML, Morley JE, Kumar VB, Allan Butterfield D (2013) Antisense directed against PS-1 gene decreases brain oxidative markers in aged senescence accelerated mice (SAMP8) and reverses learning and memory impairment: A proteomics study. Free Radic Biol Med 65, 1-14.
25. Hammond RS, Tull LE, Stackman RW (2004) On the delay-dependent involvement of the hippocampus in object recognition memory. Neurobiol Learn Mem 82, 26-34.
26. Farr SA, Erickson MA, Niehoff ML, Banks WA, Morley JE (2014) Central and peripheral administration of antisense oligonucleotide targeting amyloid precursor protein improves learning and memory and reduces neuroinflammatory cytokines in Tg2576 (APPswe) mice. J Alzheimers Dis 40, 1005-1016.
27. Farr SA, Ripley JL, Sultana R, Zhang Z, Niehoff ML, Platt TL, Murphy MP, Morley JE, Kumar V, Butterfield DA (2014) Antisense oligonucleotide against GSK-3β in brain of SAMP8 mice improves learning and memory and decreases oxidative stress: Involvement of transcription factor Nrf2 and implications for Alzheimer disease. Free Radic Biol Med 67, 387-395.
28. Quinn LS, Anderson BG, Conner JD, Wolden-Hanson T (2012) IL-15 overexpression promotes endurance, oxidative energy metabolism, and muscle PPARβ, SIRT1, PGC-1β, and PGC-1β expression in male mice. Endocrinology 154, 232-245.
29. Baskin DG, Porte D, Guest K, Dorsa DM (1983) Regional concentrations of insulin in the rat brain. Endocrinology 112, 898-903.
30. Hill JM, Lesniak MA, Pert CB, Roth J (1986) Autoradiographic localization of insulin receptors in rat brain: Prominence in olfactory and limbic areas. Neuroscience 17, 1127-1138.
31. Banks WA, Farr SA, Morley JE (2000) Permeability of the blood-brain barrier to albumin and insulin in the young and aged SAMP8 mouse. J Gerontol A Biol Sci Med Sci 55, B601-B606.
32. Banks WA, Kastin AJ (1998) Differential permeability of the blood-brain barrier to two pancreatic peptides: Insulin and amylin. Peptides 19, 883-889.
33. Baura GD, Foster DM, Porte D Jr., Kahn SE, Bergman RN, Cobelli C, Schwartz MW (1993) Saturable transport of insulin from plasma into the central nervous system of dogs in vivo. A mechanism for regulated insulin delivery to the brain. J Clin Invest 92, 1824-1830.
34. Banks WA, Jaspan JB, Huang W, Kastin AJ (1997) Transport of insulin across the blood-brain barrier: Saturability at euglycemic doses of insulin. Peptides 18, 1423-1429.
35. Hopkins DFC, Williams G (1997) Insulin receptors are widely distributed in human brain and bind human and porcine insulin with equal affinity. Diabetic Med 14, 1044-1050.
36. Verspohl EJ (2006) Effect of PAO (phenylarsine oxide) on the inhibitory effect of insulin and IGF-1 on insulin release from INS-1 cells. Endocrine J 53, 21-26.
37. Falcone JA, Salameh TS, Yi X, Cordy BJ, Mortell WG, Kabanov AV, Banks WA (2014) Intranasal administration as a route for drug delivery to the brain: Evidence for a unique pathway for albumin. J Pharmacol Exp Ther 351, 54-60.
38. Banks WA, Farr SA, Morley JE, Wolf KM, Geylis V, Steinitz M (2007) Anti-Amyloid beta protein antibody passage across the blood-brain barrier in the SAMP8 mouse model of Alzheimers disease: An age-related selective uptake with reversal of learning impairment. Exp Neurol 206, 248-256.
39. Farr SA, Poon HF, Dogrukol-Ak D, Drake J, Banks WA, Eyerman E, Butterfield DA, Morley JE (2003) The antioxidants β-lipoic acid and N-Acetylcysteine reverse memory impairment and brain oxidative stress in aged SAMP8 mice. J Neurochem 84, 1173-1183.
40. Poon HF, Joshi G, Sultana R, Farr SA, Banks WA, Morley JE, Calabrese V, Butterfield DA (2004) Antisense directed at the Aβ region of APP decreases brain oxidative markers in aged senescence accelerated mice. Brain Res 1018, 86-96.
41. Morley JE, Armbrecht HJ, Farr SA, Kumar VB (2012) The senescence accelerated mouse (SAMP8) as a model for oxidative stress and Alzheimers disease. Biochim Biophys Acta 1822, 650-656.
42. Erickson MA, Niehoff ML, Farr SA, Morley JE, Dillman LA, Lynch KM, Banks WA (2012) Peripheral administration of antisense oligonucleotides targeting the amyloid-β protein precursor reverses AβPP and LRP-1 overexpression in the aged SAMP8 mouse brain. J Alzheimers Dis 28, 951-960.
43. Davis MC, Lee J, Horan WP, Clarke AD, McGee MR, Green MF, Marder SR (2013) Effects of single dose intranasal oxytocin on social cognition in schizophrenia. Schizophr Res 147, 393-397.
44. During MJ, Cao L, Zuzga DS, Francis JS, Fitzsimons HL, Jiao X, Bland RJ, Klugmann M, Banks WA, Drucker DJ, Haile CN (2003) Glucagon-like peptide-1 receptor is involved in learning and neuroprotection. Nat Med 9, 1173-1179.