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New study reveals how the brain forms memories

[Mar. 31, 2023: JJ Shavit, The Brighter Side of News]

One of the most fascinating aspects of the brain is memory, which allows us to store, retrieve and use information learned throughout our lives. (CREDIT: iStock Photo)

The human brain is an enigma, a complex and intricate system that scientists have been trying to decipher for decades. One of the most fascinating aspects of the brain is memory, which allows us to store, retrieve and use information learned throughout our lives.

Memory is not a single process but a collection of mechanisms that work together to form, consolidate and retrieve memories. In recent years, researchers have made significant strides in understanding how memories are formed and stored in the brain.


Now, a team of researchers at the UC Davis School of Medicine has identified an intricate molecular process involving gene expression in the neurons that appears to play a critical role in memory consolidation. The study, led by Professor Yang K. Xiang, was published in the journal Science Signaling.

“This is an exciting mechanism. It shows that an enzyme like phosphodiesterase is key in controlling gene expression necessary for memory consolidation,” said Xiang.


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The researchers focused on the central adrenergic system, which controls the ability to pay attention, essential for learning and memory. Specifically, they looked at beta-2 adrenergic receptors found on nerve cells in the hippocampal region of the brain. The researchers found that when these receptors are activated, they stimulate the nucleus of the neuron to export an enzyme, phosphodiesterase 4D5 (PDE4D5).

Previous studies have identified PDE4D5 as having a role in promoting learning and memory. A crucial step to stimulating this memory-related gene expression is the attachment of a phosphate group to the receptor, known as phosphorylation. This is accomplished by an enzyme known as a kinase.


The researchers used genetically altered mice to test whether phosphorylation of the beta-2 adrenergic receptors by G-protein receptor kinase was necessary for gene expression - the export of the PDE4D5 enzyme.

The mice lacked a phosphorylation site on their beta-2 adrenergic receptors, meaning their neurons could not follow the normal signaling pathway when the receptors were activated. The researchers found that, as expected, these genetically altered mice exhibited poor memory related to space and location, the same memory pathway that is disrupted during the early stages of Alzheimer’s disease.

UC Davis Professor Yang K. Xiang’s research focuses on understanding how dysregulation of cellular and molecular mechanisms leads to diseases. (CREDIT: University of California)

However, when they provided the memory-impaired mice with a drug known as a PDE4 inhibitor, the mice’s ability to learn and retain memories was increased. The drug works by inhibiting the breakdown of cyclic AMP, a molecule that helps regulate various cellular processes, including gene expression. By inhibiting PDE4, the drug enhances cyclic AMP signaling, which leads to increased gene expression and improved memory consolidation.


“The gene expression forms the material foundation of the memory in your brain. If you don't have gene expression, you won't have memory,” Xiang explained.

The use of PDE inhibitors is being explored for Alzheimer’s disease. Studies of the PDE5 inhibitor sildenafil, known as Viagra, have had mixed results. A 2021 NIH study found Viagra was associated with a reduced risk of Alzheimer’s disease, but a later study found Viagra was not associated with lower Alzheimer’s risk.

The left panel shows PDE4D5 in the nucleus of hippocampal neurons. The right panel shows PDE4D5 in the cytoplasm of hippocampus neurons after activation of an adrenaline receptor. (CREDIT: University of California)

“We need to understand what is causing impairment in diseases like Alzheimer’s so we can find interventions that allow patients to regain ability or slow down the disease progression,” said Xiang. “This study highlights the potential of PDE inhibitors in rescuing memory in Alzheimer’s patients.”


Alzheimer’s disease is a devastating neurodegenerative disorder that affects millions of people worldwide. It is characterized by a progressive decline in memory, thinking and other cognitive functions. Despite decades of research, there is still no cure for Alzheimer’s disease.

Current treatments can only manage the symptoms, and they have limited efficacy. Therefore, there is an urgent need for new and effective therapies that can target the underlying molecular mechanisms involved in the development of Alzheimer's disease and other memory-related disorders.

The discovery of the role of PDE inhibitors in memory consolidation is an exciting development in this field of research, as it offers a potential new avenue for the treatment of memory-related disorders such as Alzheimer's disease.

However, it is important to note that the use of PDE inhibitors for the treatment of Alzheimer's disease is still in its early stages, and further research is needed to fully understand their potential benefits and limitations.

This study represents an important step forward in our understanding of the molecular mechanisms involved in memory consolidation. By shedding new light on this process, the study offers hope for the development of new and effective therapies for the treatment of memory-related disorders, including Alzheimer's disease.


As researchers continue to uncover the underlying causes of these disorders, we can hope for a future where effective treatments are available to improve the lives of those affected by memory loss and other cognitive impairments.

For more science news stories check out our New Discoveries section at The Brighter Side of News.


Note: Materials provided above by The Brighter Side of News. Content may be edited for style and length.


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