IGF Signaling Enhances Synaptic Plasticity in Hippocampal Neurons

Monday - August 7 2023, 11:25 UTC - 1 year ago

Scientists at the Max Planck Institute discovered a mechanism where the insulin superfamily of hormones, specifically IGF1 and IGF2, are locally produced and released by neurons during synaptic plasticity, promoting memory formation and cognitive health. This breakthrough could potentially guide future research in combating cognitive decline and Alzheimer’s disease.

Scientists at the Max Planck Institute discovered a mechanism where the insulin superfamily of hormones, specifically IGF1 and IGF2, are locally produced and released by neurons during synaptic plasticity, promoting memory formation and cognitive health. This breakthrough could potentially guide future research in combating cognitive decline and Alzheimer’s disease.

The insulin superfamily of hormones, which includes insulin, insulin-like growth factor 1 (IGF1), and insulin-like growth factor 2 (IGF2), has a crucial role in not only regulating blood sugar, metabolism, and growth, but also in promoting healthy brain development and function, particularly learning and memory.

These hormones can enter the brain from the liver through the bloodstream or be synthesized directly in neurons and glial cells within the brain. They bind to receptors such as the IGF1-Receptor, activating signals that modulate neuron growth and activity. A disruption in this signaling pathway can contribute to cognitive decline and diseases such as Alzheimer’s.

In an effort to understand how IGF1 and IGF2 promote brain health, scientists explored the activation of this signaling pathway in the hippocampus, a region of the brain crucial for learning and memory. More specifically, they sought to determine whether IGF signaling was active during synaptic plasticity, the cellular process that strengthens connections between neurons during memory formation and guards against cognitive decline.

To facilitate this, scientists from the Max Planck Institute developed a biosensor to detect when the IGF1-Receptor was active. This allowed them to visualize the activity of the signaling pathway involved in plasticity. When a synapse was undergoing plasticity, the scientists observed that the IGF1-Receptor was robustly activated in the strengthening synapse and nearby synapses. This receptor activation was critical for synaptic growth and strengthening during plasticity. However, where the IGF that activates the receptor was coming from was unknown.

However, Dr. Xun Tu, lead researcher and first author of the scientific publication, described how being able to visualize the receptor activation during plasticity gave them a clue. "The fact that the activation of the IGF-Receptor was localized near the synapse undergoing plasticity suggested that IGF1 or IGF2 might be produced in hippocampal neurons and locally released during plasticity," she explained.

To investigate this hypothesis, the scientists tested whether IGF1 and IGF2 were produced and could be released from hippocampal neurons. Interestingly, they discovered a region-specific difference in the production of IGF1 and IGF2. One group of neurons in the hippocampus, CA1 neurons, produced IGF1; another group, CA3 neurons, produced IGF2. When either CA1 or CA3 neurons were activated in a way that mimicked synaptic plasticity, IGF was released. Importantly, when the scientists disrupted the ability of the neurons to produce IGF, the activation of the IGF1-Receptor during plasticity and synaptic growth and strengthening was blocked.

Dr. Ryohei Yasuda, senior author on the publication and Max Pecz institute director, described the potential implications of this breakthrough. "By establishing a local IGF-based mechanism for synaptic plasticity, our study opens up new opportunities for understanding how neurons selectively strengthen and weaken connections. It could also guide future investigations into improving cognitive health and combatting age-related memory abnormalities and neurodegenerative conditions like Alzheimer’s." .