The prevalence of Alzheimer’s disease (AD) is projected to increase significantly over the next few decades. This is alarming given that no effective treatment options are available to prevent, treat, or manage AD. Thus, there is an urgent need to develop new therapeutic approaches to mitigate this memory-stealing disorder. In a study published in the journal Molecular Psychiatry, researchers tested the transgenerational benefits of maternal supplementation of choline, an important nutrient that may hold promise in the war against the disorder, in two generations of AD model mice. The results showed that when AD mice are given high choline in their diet, their offspring show improvements in spatial memory, compared with those receiving a normal choline regimen in the womb.
Choline is a vitamin-like essential nutrient that is naturally present in some foods and also available as a dietary supplement. It is a source of methyl groups needed for many steps in metabolism. All plant and animal cells require choline to maintain their structural integrity.
This compound is used by the body to produce acetylcholine, an important neurotransmitter essential for brain and nervous system functions including memory, muscle control and mood. Choline also plays a vital role in regulating gene expression.
It has long been recognized that choline is particularly important in early brain development.
Pregnant women are advised to maintain choline levels of 550 mg per day for the health of their developing fetus.
“There’s a twofold problem with this,” said study first author Dr. Ramon Velazquez, a researcher at Arizona State University.
“Studies have shown that about 90% of women don’t even meet that requirement.”
“Choline deficits are associated with failure in developing fetuses to fully meet expected milestones like walking and babbling. But we show that even if you have the recommended amount, supplementing with more in a mouse model gives even greater benefit.”
Indeed, when the AD mice received supplemental choline in their diet, their offspring showed significant improvements in spatial memory, which was tested in a water maze.
Subsequent examination of mouse tissue extracted from the hippocampus, a brain region known to play a central role in memory formation, confirmed the epigenetic alterations induced by choline supplementation.
Modified genes associated with microglial activation and brain inflammation, and reduced levels of an amino acid called homocysteine resulted in the observed performance improvements in spatial memory tasks.
Due to the epigenetic modifications induced by choline, the improvements carried over to the offspring of mice receiving supplemental choline in the womb.
“Choline acts to protect the brain from AD in at least two ways,” the researchers explained.
“First, choline reduces levels of homocysteine. This amino acid is known to double the risk of developing AD and is found in elevated levels in patients with AD. Choline performs a chemical transformation, converting the harmful homocysteine into the helpful chemical methionine.”
“This conversion happens thanks to an enzyme known as betaine-homocysteine methyltransferase (BMHT).”
Dr. Velazquez and colleagues found that choline supplementation increased the production of BMHT in two generations of mice.
“Secondly, choline supplementation reduces the activation of microglia — cells responsible for clearing away debris in the brain,” they said.
“While their housekeeping functions are essential to brain health, activated microglia can get out of control, as they typically do during AD. Over-activation of microglia causes brain inflammation and can eventually lead to neuronal death. Choline supplementation reduces the activation of microglia, offering further protection from the ravages of AD.”
This article originally appeared in Sci-News