More is always better, right?
Maybe not. In the case of synapses — the crucial connections between brain cells — both too many or too few may disrupt brain function.
Researchers from Princeton University and the University of California-San Diego (UCSD) recently found that an immune-system protein called MHCI, or major histocompatibility complex class I, moonlights in the nervous system to help regulate the number of synapses, which transmit chemical and electrical signals between neurons.
The researchers content that MHCI could play an pivotal role in conditions such as Alzheimer’s disease, type II diabetes, and autism.
MHCI proteins are known for their role in the immune system and their ability to fight cancer cells. In this role, the proteins allow T cells to recognize and kill infected and cancerous cells.
But in the brain, researchers found that MHCI immune molecules are one of the only known factors that limit the density of synapses, ensuring that synapses form in the appropriate numbers necessary to support healthy brain function. MHCI limits synapse density by inhibiting insulin receptors, which regulate the body’s sugar metabolism and, in the brain, promote synapse formation.
Researchers have recently found that an immune-system protein called MHCI, or major histocompatibility complex class I, moonlights in the nervous system to help regulate the number of synapses, which transmit chemical and electrical signals between neurons.
The number and location of synapses — not too many or too few — is critical to healthy brain function. The researchers found that MHCI proteins, known for their role in the immune system, also are one of the only known factors that ensure synapse density is not too high. The protein does so by inhibiting insulin receptors, which promote synapse formation.
Senior author Lisa Boulanger, an assistant professor in the Department of Molecular Biology and the Princeton Neuroscience Institute (PNI), said that MHCI’s role in ensuring appropriate insulin signaling and synapse density raises the possibility that changes in the protein’s activity could contribute to conditions such Alzheimer’s disease, type II diabetes, and autism.
“Our results suggest that changes in MHCI immune proteins could contribute to disorders of insulin resistance,” Boulanger said. “For example, chronic inflammation is associated with type II diabetes, but the reason for this link has remained a mystery. Our results suggest that inflammation-induced changes in MHCI could have consequences for insulin signaling in neurons and maybe elsewhere.”
Mapping the exact nature of the mediation may be key.
“Many people thought that immune molecules like MHCI must be missing from the brain,” Boulanger said. “It turns out that MHCI immune proteins do operate in the brain — they just do something completely different. The dual roles of these proteins in the immune system and nervous system may allow them to mediate both harmful and beneficial interactions between the two systems.”
The paper, “MHC Class I Limits Hippocampal Synapse Density by Inhibiting Neuronal Insulin Receptor Signaling,” was published the Journal of Neuroscience.
Journal citation: The Journal of Neuroscience, 27 August 2014, 34(35): 11844-11856; doi: 10.1523/JNEUROSCI.4642-12.2014