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Intranasal delivery of low-dose insulin ameliorates motor dysfunction and dopaminergic cell death in a 6-OHDA rat model of Parkinson's Disease.
Neurosci Lett 2019; 714:134567NL

Abstract

Emerging evidence continues to demonstrate that disrupted insulin signaling and altered energy metabolism may play a key role underpinning pathology in neurodegenerative conditions. Intranasally administered insulin has already shown promise as a memory-enhancing therapy in patients with Alzheimer's and animal models of the disease. Intranasal drug delivery allows for direct targeting of insulin to the brain, bypassing the blood brain barrier and minimizing systemic adverse effects. In this study, we sought to expand upon previous results that show intranasal insulin may also have promise as a Parkinson's therapy. We treated 6-OHDA parkinsonian rats with a low dose (3 IU/day) of insulin and assessed apomorphine induced rotational turns, motor deficits via a horizontal ladder test, and dopaminergic cell survival via stereological counting. We found that insulin therapy substantially reduced motor dysfunction and dopaminergic cell death induced by unilateral injection of 6-OHDA. These results confirm insulin's efficacy within this model, and do so over a longer period after model induction which more closely resembles Parkinson's disease. This study also employed a lower dose than previous studies and utilizes a delivery device, which could lead to an easier transition into human clinical trials as a therapeutic for Parkinson's disease.

Authors+Show Affiliations

HealthPartners Neuroscience Center, HealthPartners Institute, 295 Phalen Blvd., Saint Paul, MN, 55130, United States. Electronic address: jared.m.fine@healthpartners.com.HealthPartners Neuroscience Center, HealthPartners Institute, 295 Phalen Blvd., Saint Paul, MN, 55130, United States.HealthPartners Neuroscience Center, HealthPartners Institute, 295 Phalen Blvd., Saint Paul, MN, 55130, United States.HealthPartners Neuroscience Center, HealthPartners Institute, 295 Phalen Blvd., Saint Paul, MN, 55130, United States.HealthPartners Neuroscience Center, HealthPartners Institute, 295 Phalen Blvd., Saint Paul, MN, 55130, United States.HealthPartners Neuroscience Center, HealthPartners Institute, 295 Phalen Blvd., Saint Paul, MN, 55130, United States.HealthPartners Neuroscience Center, HealthPartners Institute, 295 Phalen Blvd., Saint Paul, MN, 55130, United States.HealthPartners Neuroscience Center, HealthPartners Institute, 295 Phalen Blvd., Saint Paul, MN, 55130, United States.HealthPartners Neuroscience Center, HealthPartners Institute, 295 Phalen Blvd., Saint Paul, MN, 55130, United States.HealthPartners Neuroscience Center, HealthPartners Institute, 295 Phalen Blvd., Saint Paul, MN, 55130, United States.HealthPartners Neuroscience Center, HealthPartners Institute, 295 Phalen Blvd., Saint Paul, MN, 55130, United States.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31629033

Citation

Fine, Jared M., et al. "Intranasal Delivery of Low-dose Insulin Ameliorates Motor Dysfunction and Dopaminergic Cell Death in a 6-OHDA Rat Model of Parkinson's Disease." Neuroscience Letters, vol. 714, 2019, p. 134567.
Fine JM, Stroebel BM, Faltesek KA, et al. Intranasal delivery of low-dose insulin ameliorates motor dysfunction and dopaminergic cell death in a 6-OHDA rat model of Parkinson's Disease. Neurosci Lett. 2019;714:134567.
Fine, J. M., Stroebel, B. M., Faltesek, K. A., Terai, K., Haase, L., Knutzen, K. E., ... Hanson, L. R. (2019). Intranasal delivery of low-dose insulin ameliorates motor dysfunction and dopaminergic cell death in a 6-OHDA rat model of Parkinson's Disease. Neuroscience Letters, 714, p. 134567. doi:10.1016/j.neulet.2019.134567.
Fine JM, et al. Intranasal Delivery of Low-dose Insulin Ameliorates Motor Dysfunction and Dopaminergic Cell Death in a 6-OHDA Rat Model of Parkinson's Disease. Neurosci Lett. 2019 Oct 16;714:134567. PubMed PMID: 31629033.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Intranasal delivery of low-dose insulin ameliorates motor dysfunction and dopaminergic cell death in a 6-OHDA rat model of Parkinson's Disease. AU - Fine,Jared M, AU - Stroebel,Benjamin M, AU - Faltesek,Katherine A, AU - Terai,Kaoru, AU - Haase,Lucas, AU - Knutzen,Kristin E, AU - Kosyakovsky,Jacob, AU - Bowe,Tate J, AU - Fuller,Austin K, AU - Frey,William H, AU - Hanson,Leah R, Y1 - 2019/10/16/ PY - 2019/09/04/received PY - 2019/10/11/revised PY - 2019/10/15/accepted PY - 2019/10/20/pubmed PY - 2019/10/20/medline PY - 2019/10/20/entrez KW - 6-hydroxydopamine KW - Drug-induced rotational test KW - Horizontal ladder test KW - Humulin KW - Insulin KW - Intranasal KW - Parkinson’s Disease KW - Tyrosine hydroxylase SP - 134567 EP - 134567 JF - Neuroscience letters JO - Neurosci. Lett. VL - 714 N2 - Emerging evidence continues to demonstrate that disrupted insulin signaling and altered energy metabolism may play a key role underpinning pathology in neurodegenerative conditions. Intranasally administered insulin has already shown promise as a memory-enhancing therapy in patients with Alzheimer's and animal models of the disease. Intranasal drug delivery allows for direct targeting of insulin to the brain, bypassing the blood brain barrier and minimizing systemic adverse effects. In this study, we sought to expand upon previous results that show intranasal insulin may also have promise as a Parkinson's therapy. We treated 6-OHDA parkinsonian rats with a low dose (3 IU/day) of insulin and assessed apomorphine induced rotational turns, motor deficits via a horizontal ladder test, and dopaminergic cell survival via stereological counting. We found that insulin therapy substantially reduced motor dysfunction and dopaminergic cell death induced by unilateral injection of 6-OHDA. These results confirm insulin's efficacy within this model, and do so over a longer period after model induction which more closely resembles Parkinson's disease. This study also employed a lower dose than previous studies and utilizes a delivery device, which could lead to an easier transition into human clinical trials as a therapeutic for Parkinson's disease. SN - 1872-7972 UR - https://www.unboundmedicine.com/medline/citation/31629033/Intranasal_delivery_of_low-dose_insulin_ameliorates_motor_dysfunction_and_dopaminergic_cell_death_in_a_6-OHDA_rat_model_of_Parkinson's_Disease L2 - https://linkinghub.elsevier.com/retrieve/pii/S0304-3940(19)30670-6 DB - PRIME DP - Unbound Medicine ER -