Targeting the brain through the nose: Influence of intranasal insulin application on the human olfactory system

• Applicant: Professorin Dr. Jessica Freiherr, Ph.D.
• Subject Area: Clinical Neurology; Neurosurgery and Neuroradiology
• Term: from 2013 to 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 244839636

The hormone insulin not only regulates the blood glucose level in the periphery of the human body but also functions as a neuropeptide in the central nervous system. The brain is sensitive for insulin, an enhanced cerebrospinal insulin level leads to improved declarative memory function as well as loss of body weight. Thus, insulin is considered an important metabolic key signal between the endocrine system and the brain during the regulation of food consumption. Cerebral insulin receptors in the cortex, hippocampus, hypothalamus, but also in the olfactory bulb are responsible for the effects of an increased cerebrospinal insulin level. In addition to the high amount of insulin receptors in the olfactory bulb, an important olfactory brain area, insulin receptors are also situated in the olfactory epithelium.This project proposal is based upon the hypothesis that the anorexigenic effects of the neuropeptide insulin are mediated by a modulation of the processing of olfactory signals on a peripheral or central level. For the first time we will investigate the effects of an increased cerebrospinal insulin level on olfactory perception and the underlying processes. The effects of insulin on olfactory processing in healthy subjects will be compared to the effects of a placebo. In order to deliver insulin and placebo to the brain the non-invasive method of intranasal insulin application will be utilized. With the help of behavioral studies the influence of an intranasal insulin application on different olfactory performance scores, olfactory memory processes, psychophysiological parameters during crossmodal olfactory-visual integration, and on food consumption will be compared. Within the second part of the project we will utilize functional imaging methods to further our understanding of the impact of an increased cerebrospinal insulin level on the cortical network involved in the processing of olfactory stimuli in general, olfactory memory, and crossmodal olfactory-visual integration processes.Our results provide innovative insights into the interaction of cerebrospinal insulin with the olfactory system. Conclusions on the fundamental mechanisms of insulin effects on food consumption and the mediation of satiety in healthy subjects can be drawn. On the one hand promising approaches for therapy of patients with a diminished sense of smell can be based on our results. On the other hand our results provide background information for the development of novel therapy strategies for diseases of which it is well-established that cerebrospinal insulin levels are reduced (Morbus Alzheimer) or an insulin resistance exists (overweight, adiposity).

• DFG Programme: Research Grants