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Link found between feeding and memory brain areas

By Julia Bernstein • Jan 27, 2019 at 2:00 PM

Recent research suggests there is an unexpected connection between the the feeding and memory centers of the brain — findings which could effect studies related to autism spectrum disorders, intellectual disabilities and neurodegenerative disease.

The search for a mechanism that could explain how a protein called NCOR1/2 regulates the brain’s memory revealed the connection. The findings, which were published in the journal Nature Neuroscience by a team of researchers at Baylor College of Medicine, have implications for studies on brain function, including those related to autism spectrum disorders, intellectual disabilities and neurodegenerative disease.

“It was not known how NCOR1/2 regulates memory or other cognitive functions, but there is evidence that NCOR1/2 plays a fundamental role in the activity of many hormones,” said corresponding author Dr. Zheng Sun.

In this project, the researchers worked with mice carrying mutations of NCOR1/2.

“These mice clearly present with memory deficits,” said co-first author Dr. Wenjun Zhou, a postdoctoral associate in the Sun lab. Zhou said when the NCOR1/2 protein was disrupted, it caused dysfunctions in brain’s feeding center. 

To understand the cause, Sun collaborated with Dr. Yong Xu, an associate professor of pediatrics, molecular and cellular biology and with the USDA/ARS Children's Nutrition Research Center at Baylor College of Medicine.

The researchers conducted a number of electrophysiological experiments to investigate how the lack of NCOR1/2 resulted in memory deficits in mice.

“What struck us the most was that the process by which NCOR1/2 regulates memory involves a new circuit that links two brain regions: the lateral hypothalamus, known as a feeding center of the brain, and the hippocampus, a place that stores memory,” Xu said. “It surprised us because the hypothalamus is not traditionally considered to be a major regulator of learning and memory.”

The researchers validated the newly discovered circuits in several different ways, resulting in the same conclusion. The protein is a key component to this newly discovered feeding-memory connection. In fact, the verify the connection, the research team found the connection became dysfunctional if the protein was knocked out.

The researchers connected their findings in mouse models with human conditions.

“We describe here new genetic variants of NCOR1/2 in patients with intellectual disability or neurodevelopmental defects,” said co-corresponding author Dr. Pengfei Liu, assistant professor of molecular and human genetics at Baylor and laboratory director of clinical research at Baylor Genetics.

“The gene NCOR1 is located on human chromosome 17, very close to the region that has been previously implicated in the Potocki–Lupski and Smith–Magenis syndromes,” Liu explains. “We have always suspected that mutations of this gene could cause intellectual disabilities or other deleterious neurological consequences.

“The mouse models in the current study provide the first evidence that this is indeed the case.”

These findings create meaning for the relationships between endocrine factors, obesity and metabolic disorders and cognitive dysfunctions like Alzheimer’s disease.

It is known, for example, that people with endocrine disruption or metabolic disorders are more susceptible to Alzheimer’s disease.

“Mechanisms underlying these associations are not completely clear,” Sun said. “We think that the NCOR1/2-regulated neural circuit between the feeding and the memory centers of the brain we have discovered is worth exploring further in this context.”

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