Distribution of insulin in trigeminal nerve and brain after intranasal administration

Abstract

In the brain, insulin acts as a growth factor, regulates energy homeostasis, and is involved in learning and memory acquisition. Many central nervous system (CNS) diseases are characterized by deficits in insulin signaling. Pre-clinical studies have shown that intranasal insulin is neuroprotective in models of Alzheimer’s disease, Parkinson’s disease, and traumatic brain injury. Clinical trials have also shown that intranasal insulin elicits beneficial cognitive effects in patients with Alzheimer’s disease. It is known that insulin can be detected in the CNS within minutes following intranasal administration. Despite these advances, the anatomical pathways that insulin utilizes to reach the CNS and the cellular CNS targets after intranasal administration are not fully understood. Here, we intranasally administered fluorescently labeled insulin and imaged its localization within the brain and trigeminal nerves. Our data indicates that intranasal insulin can reach cellular CNS targets along extracellular components of the trigeminal nerve. Upon CNS entry, we found insulin significantly increased levels of an activated form of the insulin receptor. These findings suggest that the intranasal route of administration is able to effectively deliver insulin to CNS targets in a biologically active form.

Neurological manifestations of patients with COVID-19: potential routes of SARS-CoV-2 neuroinvasion from the periphery to the brain

“…This is supported by evidence from animal experiments investigating MERS-CoV [17] and SARS-CoV [19]. Alternatively, SARS-CoV-2 adhering to the nasal mucosa may infect the trigeminal nerve (a nasal cavity nociceptor), which has been investigated for drug delivery [20,21]. In addition, postmortem analyses of SARS patients from 2003 detected SARS-CoV particles in the brain that showed cellular selectivity, most assembling in neurons rather than glia [22][23][24].…”

Unraveling the Possible Routes of SARS-COV-2 Invasion into the Central Nervous System

“…SARS-CoV-2 might also be transferred to the CNS through the trigeminal nerve, which innervates nociceptive cells in the nasal cavity, and has been successfully tested for drug transportation [ 96 , 97 ]. Sensory nerve endings of the trigeminal nerve also exist in the conjunctiva, where SARS-CoV-2 RNA fragments have been found in a patient with conjunctivitis [ 98 ], and in the taste buds, ascending not only in trigeminal nuclei, but also to the nuclei of the solitary tract [ 59 ].…”

Role of Insulin in Neurotrauma and Neurodegeneration: A Review

“…Free nerve endings of branches from the trigeminal nerve are also present in the nasal epithelium (Finger et al, 1990). Insulin is transported along the olfactory and trigeminal nerves by intracellular pathways, via endocytosis by the nerve then anterograde transport, or extracellular pathways, via paracellular diffusion (Thorne et al, 1995;Baker and Spencer, 1986;Born et al, 2002;Renner et al, 2012;Lochhead et al, 2015;Lochhead et al, 2019).…”