Intranasal insulin treatment improves memory and learning in a rat amyloid-beta model of Alzheimer’s disease

Abstract

Recently, insulin has been used as a pro-cognitive agent for the potential treatment of Alzheimer's disease (AD), because of its ability to cross the brain-blood barrier (BBB) by a saturable transport system. This study has been designed to evaluate the effects of intranasal insulin regimen, as a bypass system of BBB, on spatial memory in amyloid-beta (Aβ) model of AD in rat. Unilateral infusion of Aβ 25-35 (10 nmol/2 μl/rat) into the lateral ventricular region of brain was used to produce a rat model of AD. After a 24-h recovery period, rats received insulin or vehicle via intraperitoneal or intranasal route (0.1, 0.2, and 0.3 IU) for 14 days. Memory function in rats was assessed by Morris water maze test, with 5 days of training and consequent probe test protocol. Different doses of intraperitoneal insulin did not have a significant effect on learning and memory in AD rats. However, intranasal insulin at doses of 0.2 and 0.3 IU improved the learning and memory in Aβ-received rats.In conclusion, intranasal insulin as a non-invasive strategy improves spatial learning and memory in AD model.

Repurposing of Anti-Diabetic Agents as a New Opportunity to Alleviate Cognitive Impairment in Neurodegenerative and Neuropsychiatric Disorders

“…Fourteen consecutive days of intranasal insulin treatment could prevent the severe memory and learning impairment induced by intracerebroventricular administration of Aβ, which was a rat model of AD( Farzampour et al, 2016 ). In transgenic mouse model of AD, intranasal insulin improved cognitive impairment through promotion of neurogenesis, alleviation of Aβ pathology and enhancement of insulin signaling( Mao et al, 2016 ).…”

Nicotine Modulates Cognitive Function in D-Galactose-Induced Senescence in Mice

“…Intranasal drug delivery is a novel and safe way to administer medications through the nasal mucosa (Farzampour et al, 2016 ). This route of drug administration shunts the BBB, is non-invasive and encompasses two separate pathways including trans-neuronal or immediate and para-neuronal or delayed (Mustafa et al, 2016 ).…”

“…The delivery is non-invasive, bypasses blood-brain barrier (BBB), allowing the drug to target the olfactory region as the direct avenue from nose to the brain. In the case of nicotine, the intranasal route is an alternative choice for delivery of nicotine to the brain (Farzampour et al, 2016 ; Pourmemar et al, 2017 ).…”

Physical activity and beta-amyloid pathology in Alzheimer's disease: a sound mind in a sound body

“…APP is an integral membrane glycoprotein that is expressed in the CNS. APP is sequentially cleaved by β-secretase (BACE1) and γ-secretase to generate Aβ (Cole and Vassar, 2007[ 9 ]; Farzampour et al, 2016[ 25 ]). Increased Aβ production by sequential cleavage of APP by β and γ-secretases contributes to the etiological basis of AD (Joshi and Wang, 2015[ 36 ]).…”