Effects of Insulin-Like Growth Factor-1 on Neurotransmitters for Memory

Overview

Background: Alzheimer’s dementia (AD) is the most common dementia affecting over 5.7 million in US. People with diabetes are of great interest in this area since they have five-fold risk of developing AD. Insulin is the endogenous hormone that regulates blood sugar level, and has previously been shown to affect neurotransmission. But little is known in this regard about a structurally similar protein that exists in the adult nervous system: insulin-like growth factor 1 (IGF1). Glutamate, the most common neurotransmitter, binds to α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. Another class of glutamate receptors, N-methyl-D-aspartate (NMDA) are also important in learning and memory. This project aims to determine what class of glutamate receptor is being affected by IGF1 by using receptor agonists and antagonists. Hypothesis: If IGF1 is added to the rat cortical neuronal cells in the presence of glutamate, then it would modify the flux of intracellular calcium concentration, because of glutamate’s activation of its two major classes of receptor: NMDA and AMPA. Methods: Rat cortical neuron cell cultures were prepared and monitored for intracellular calcium levels under standardized conditions at regular intervals during application of glutamate receptor agonists in the presence or absence of insulin, IGF-1, and inhibitors of specific glutamate receptors (e.g., CNQX). Results: The average ± SD of calcium influx with control was 175.6 ± 22.1 Nano Molars (nM). In contrast to insulin, calcium influx in response to glutamate was significantly inhibited by IGF1 (125.2 ± 28.6 nM). However, when NMDA receptors were isolated by the application of CNQX, the calcium influx through this class of receptor was elevated (408.5 ±17.9 nM), consistent with the effects of insulin. Isolation of AMPA receptors by APV showed reduction in calcium influx (164.8 ±19.3 nM), indicating that they were responsible for the main effect of IGF1 on responses to glutamate. Conclusion: IGF1 influences NMDA receptors similarly to insulin but has an opposite effect on the overall response to glutamate in cultures of rat cortical neurons. This indicates IGF1 has a unique role in processes related to neurotransmission and perhaps memory in AD.

Competition history

• AJAS 2020 Category not listed

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