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Intranasal Insulin Administration Ameliorates Streptozotocin (ICV)-Induced Insulin Receptor Dysfunction, Neuroinflammation, Amyloidogenesis, and Memory Impairment in Rats.
Mol Neurobiol. 2017 Oct; 54(8):6507-6522.MN

Abstract

Alzheimer's disease (AD) is associated with reduced insulin level and impairment of insulin receptor (IR) signaling in the brain, which correlates to amyloid pathology, neuroinflammation, and synaptic neurotoxicity. Clinical studies show that intranasal insulin improves memory in AD patients without peripheral hypoglycemia. However, neuroprotective molecular mechanism of the beneficial effect of intranasal insulin in AD pathology is unexplored. Therefore, we investigated the role of intranasal insulin on intracerebroventricular (ICV) streptozotocin (STZ)-induced memory impairment in rats as evaluated in the Morris water maze test. STZ (ICV) treated rats had shown memory impairment along with a significant decrease in IR signaling molecules (IR, pIRS-1, pAkt, and pGSK-3α/β expression) and IDE expression in both hippocampus and cerebral cortex. Intranasal insulin delivery prevented these changes. Moreover, intranasal insulin was found to inhibit significantly glial cell activation (GFAP and Iba-1 expression), neuroinflammation (COX-2 expression, NFκB translocation, TNF-α, and IL-10 level) and amyloidogenic protein expression (BACE-1 and Aβ1-42 expression) in STZ (ICV)-injected rats. STZ (ICV)-induced caspase activation and postsynaptic neurotoxicity were also prevented by treatment with intranasal insulin. Our findings reveal that insulin has the neuroprotective effect and clearly signifies the potential use of intranasal insulin delivery for the treatment of AD. Graphical Abstract Neuroprotective effects of intranasal insulin administration on streptozotocin (ICV)-induced memory impairment in rats.

Authors+Show Affiliations

Divisions of Pharmacology and Toxicology, CSIR-Central Drug Research Institute, Lucknow, 226031, India. Academy of Scientific and Innovative Research (AcSIR), Chennai, India.Divisions of Pharmacology and Toxicology, CSIR-Central Drug Research Institute, Lucknow, 226031, India. Academy of Scientific and Innovative Research (AcSIR), Chennai, India.Divisions of Pharmacology and Toxicology, CSIR-Central Drug Research Institute, Lucknow, 226031, India. Academy of Scientific and Innovative Research (AcSIR), Chennai, India.Divisions of Pharmacology and Toxicology, CSIR-Central Drug Research Institute, Lucknow, 226031, India. rakeshshuklacdri@gmail.com. Academy of Scientific and Innovative Research (AcSIR), Chennai, India. rakeshshuklacdri@gmail.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27730514

Citation

Rajasekar, N, et al. "Intranasal Insulin Administration Ameliorates Streptozotocin (ICV)-Induced Insulin Receptor Dysfunction, Neuroinflammation, Amyloidogenesis, and Memory Impairment in Rats." Molecular Neurobiology, vol. 54, no. 8, 2017, pp. 6507-6522.
Rajasekar N, Nath C, Hanif K, et al. Intranasal Insulin Administration Ameliorates Streptozotocin (ICV)-Induced Insulin Receptor Dysfunction, Neuroinflammation, Amyloidogenesis, and Memory Impairment in Rats. Mol Neurobiol. 2017;54(8):6507-6522.
Rajasekar, N., Nath, C., Hanif, K., & Shukla, R. (2017). Intranasal Insulin Administration Ameliorates Streptozotocin (ICV)-Induced Insulin Receptor Dysfunction, Neuroinflammation, Amyloidogenesis, and Memory Impairment in Rats. Molecular Neurobiology, 54(8), 6507-6522. https://doi.org/10.1007/s12035-016-0169-8
Rajasekar N, et al. Intranasal Insulin Administration Ameliorates Streptozotocin (ICV)-Induced Insulin Receptor Dysfunction, Neuroinflammation, Amyloidogenesis, and Memory Impairment in Rats. Mol Neurobiol. 2017;54(8):6507-6522. PubMed PMID: 27730514.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Intranasal Insulin Administration Ameliorates Streptozotocin (ICV)-Induced Insulin Receptor Dysfunction, Neuroinflammation, Amyloidogenesis, and Memory Impairment in Rats. AU - Rajasekar,N, AU - Nath,Chandishwar, AU - Hanif,Kashif, AU - Shukla,Rakesh, Y1 - 2016/10/11/ PY - 2016/03/15/received PY - 2016/09/27/accepted PY - 2016/10/13/pubmed PY - 2018/7/10/medline PY - 2016/10/13/entrez KW - Amyloidogenic protein expression KW - Glial activation KW - Insulin receptor dysfunction KW - Intranasal insulin KW - post synaptic neurotoxicity SP - 6507 EP - 6522 JF - Molecular neurobiology JO - Mol. Neurobiol. VL - 54 IS - 8 N2 - Alzheimer's disease (AD) is associated with reduced insulin level and impairment of insulin receptor (IR) signaling in the brain, which correlates to amyloid pathology, neuroinflammation, and synaptic neurotoxicity. Clinical studies show that intranasal insulin improves memory in AD patients without peripheral hypoglycemia. However, neuroprotective molecular mechanism of the beneficial effect of intranasal insulin in AD pathology is unexplored. Therefore, we investigated the role of intranasal insulin on intracerebroventricular (ICV) streptozotocin (STZ)-induced memory impairment in rats as evaluated in the Morris water maze test. STZ (ICV) treated rats had shown memory impairment along with a significant decrease in IR signaling molecules (IR, pIRS-1, pAkt, and pGSK-3α/β expression) and IDE expression in both hippocampus and cerebral cortex. Intranasal insulin delivery prevented these changes. Moreover, intranasal insulin was found to inhibit significantly glial cell activation (GFAP and Iba-1 expression), neuroinflammation (COX-2 expression, NFκB translocation, TNF-α, and IL-10 level) and amyloidogenic protein expression (BACE-1 and Aβ1-42 expression) in STZ (ICV)-injected rats. STZ (ICV)-induced caspase activation and postsynaptic neurotoxicity were also prevented by treatment with intranasal insulin. Our findings reveal that insulin has the neuroprotective effect and clearly signifies the potential use of intranasal insulin delivery for the treatment of AD. Graphical Abstract Neuroprotective effects of intranasal insulin administration on streptozotocin (ICV)-induced memory impairment in rats. SN - 1559-1182 UR - https://www.unboundmedicine.com/medline/citation/27730514/Intranasal_Insulin_Administration_Ameliorates_Streptozotocin__ICV__Induced_Insulin_Receptor_Dysfunction_Neuroinflammation_Amyloidogenesis_and_Memory_Impairment_in_Rats_ L2 - https://dx.doi.org/10.1007/s12035-016-0169-8 DB - PRIME DP - Unbound Medicine ER -