Low-dose intranasal insulin improves cognitive function and suppresses the development of epilepsy

• Published in: Brain research 2020-01, Vol.1726, p.146474, Article 146474
• Main Authors: Peng, Shu, Yang, Jin, Wang, Yufeng, Fan, Yang, Tang, Feng, Hou, Changyue, Yu, Juming, Wang, Xiaoming, Jiang, Guohui
• Format: Article
• Language: English
• Subjects: Administration, Intranasal; Animals; Anticonvulsants - administration & dosage; Brain - drug effects; Brain - physiopathology; Cognition - drug effects; Cognitive function; Epilepsy; Epilepsy - chemically induced; Epilepsy - prevention & control; Epilepsy - psychology; Epileptic seizures; Insulin - administration & dosage; Intranasal insulin; Kainic Acid - administration & dosage; Male; Mice, Inbred C57BL; Pentylenetetrazole - administration & dosage; Seizures - chemically induced; Seizures - prevention & control; Seizures - psychology; Theta activity
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2019.146474

•Intranasal insulin has neuroprotective effects on a variety of neurological diseases.•This study demonstrates the effects of intranasal insulin on epileptic activity and its potential neuroprotective effects.•Low intranasal doses reduced seizure frequency and epileptic discharge in mice.•The same doses also increased GABA levels and hippocampal theta activities.•Mice treated with low-dose intranasal insulin showed improved spatial memory. Intranasal insulin exerts neuroprotective effects in a variety of neurological diseases. Whether intranasal insulin affects epileptic activity and whether it has neuroprotective effects in epileptic diseases is however still unknown. In this study we show that low-dose intranasal insulin inhibited kainic acid (KA)- or pentylenetetrazole (PTZ)-induced acute seizures and reduced epileptic discharge activities in mice, potentially by alleviating the increase in seizure-induced glutamate in the hippocampus. Meanwhile, intranasal insulin increased GABA levels and the activities of hippocampal theta, which may affect the excitability of the hippocampus. In chronic KA-induced epilepsy, low-dose intranasal insulin reduces the frequency of spontaneous recurrent seizures and epileptic discharges, while it increases theta energy and thereby improves spatial memory. Larger doses of intranasal insulin increased the frequency of seizures but did not aggravate cognitive impairment, suggesting that the frequency of seizures may not be related to impaired cognitive function. Overall, our findings show that low-dose intranasal insulin inhibits epileptic events and improves cognitive impairment in epileptic mice, suggesting that learning and memory can be improved by intranasal insulin. However, larger doses might increase the risk of epileptic seizures.