"Kidney Cells Can Retain Memory, Just Like Brain Cells"

"Scientists have discovered the molecular processes behind memory functioning in cells beyond the nervous system."

"Human embryonic kidney cells share similar molecular processes to those found in neurons that form memories."

Kidney cells, typically associated with filtering waste and maintaining fluid balance, are now showing that they have an unexpected ability to "remember" patterns, a discovery that could reshape our understanding of cellular function and memory. While the brain and its neurons have long been the focus when it comes to memory and information storage, recent research reveals that kidney cells, located far from the brain, can also store and recognize patterns in ways strikingly similar to neurons.

This groundbreaking finding, published in Nature Communications on November 7, challenges our traditional views of memory, but not in the way one might think. As neuroscientist Nikolay Kukushkin of New York University explains, the research does not suggest that kidney cells contribute to the complex processes of remembering how to ride a bike or recall past experiences, like childhood memories. Instead, this discovery adds a new layer of understanding to the broader concept of memory, one that doesn't necessarily require a brain but still involves a form of information storage and pattern recognition at the cellular level.

The ability of kidney cells to "remember" is tied to their response to certain molecular signals. In their research, scientists observed that kidney cells could adjust their behavior in response to these signals in a way that reflected a kind of cellular "learning" process. This process, however, differs from how neurons process and store information in the brain. It suggests that cellular memory might be more widespread in the body than previously thought, extending beyond the nervous system and offering a more complex view of how cells interact with and respond to their environment.

Although this discovery doesn't imply that kidneys are involved in cognitive memory or conscious thought, it opens up new avenues for understanding how cells across the body can "remember" and adapt to stimuli. By broadening the concept of memory beyond neurons and the brain, this research could have implications for a variety of fields, including cellular biology, disease research, and even medical treatments. It challenges scientists to think beyond the brain when considering how memory, adaptation, and learning might work on a molecular scale throughout the body.

In a series of experiments, the kidney cells displayed a phenomenon known as the "massed-space effect," which is a well-established feature of memory processing in the brain. This effect refers to the way information is stored in small, manageable chunks over time, rather than being crammed into the brain all at once. It's a strategy that helps improve how memories are formed and retained, and it seems that kidney cells might use a similar approach, suggesting that their capacity for memory isn't entirely different from what we see in neurons.

Beyond the brain, cells throughout the body must also keep track of various signals and changes in their environment. One of the key players in this process is a protein called CREB, which is central to how memories are processed. CREB and other molecular components involved in memory are not limited to neurons; they are found in a variety of cells across the body, including those in the kidneys. While these cells share similar molecular machinery with neurons, the researchers were uncertain whether the parts worked the same way in nonneuronal cells like those in the kidneys.

The idea that kidney cells might use the same molecular tools for memory processing as neurons is an exciting one, but it also raised questions about how those tools function outside of the brain. Would kidney cells use CREB and related proteins in the same way neurons do to store and process information? The researchers set out to find answers to these questions, exploring whether these molecular components in the kidneys could function in ways similar to their role in the brain. While the study doesn't suggest that kidneys "remember" the way we think of memories in a human sense, it does highlight the versatility of the cellular machinery involved in memory, showing that this kind of molecular processing might be more widespread in the body than previously understood.

In neurons, when a chemical signal is received, the cell starts producing a protein called CREB. This protein then activates additional genes, causing changes in the cell that help create and store memories, essentially kick starting the brain's molecular memory process. Intrigued by this, Kukushkin and his team wanted to find out if non-neuronal cells, like those in the kidneys, respond to signals in the same way, particularly when it comes to the role of CREB.

To explore this, the researchers inserted an artificial gene into human embryonic kidney cells. This gene was designed to closely resemble a natural stretch of DNA that CREB typically activates when it binds to it what the researchers referred to as a "memory gene." Along with this gene, the researchers added instructions to produce a glowing protein, the same kind found in fireflies, so they could track the gene's activity.

Once the modified kidney cells were prepared, the team exposed them to artificial chemical signals designed to mimic the type of signals that would normally activate memory processes in neurons. The more light the glowing protein emitted, the stronger the researchers knew the "memory gene" had been turned on. By measuring this light, Kukushkin and his team could track how the cells responded and whether they showed signs of activating a memory-like process, similar to how neurons function.

This experiment was designed to test if kidney cells could use the same molecular machinery to process information, similar to neurons. The glowing protein provided a visible marker, allowing the researchers to directly measure the activation of memory related genes in response to specific signals, giving them insight into how cellular memory might work in  non neuronal cells.

The researchers found that different timing patterns of chemical pulses led to different responses in the kidney cells. When they applied four, three-minute pulses spaced 10 minutes apart, the cells showed a stronger light output 24 hours later compared to cells that received a single 12-minute pulse in one go. This result is known as the "massed-spaced effect," which had previously only been observed in neurons and was thought to be a unique property of brain cells involved in memory formation.

Kukushkin pointed out that this effect had never been seen outside the brain before. “It’s always been thought of as something specific to neurons, something essential for how memory is formed in the brain,” he said. “But we’re suggesting that, if nonbrain cells are given complex enough tasks, they might also have the ability to form some kind of memory.”

Neuroscientist Ashok Hegde called the study "interesting," noting that the researchers were applying a principle from neuroscience in a broader context, aiming to understand gene expression in cells that aren't neurons. However, Hegde also pointed out that it's still uncertain how widely the findings could apply to other types of cells. Despite this, he sees the research as potentially valuable in future applications, especially for developing treatments for diseases involving memory loss. This discovery could eventually help identify new drug targets to address conditions where memory function is impaired.

Kukushkin agrees with the broader implications of this discovery. He suggests that the body has the capacity to store information, and that could have important consequences for health. 

"For example, we might consider cancer cells as having a kind of memory," Kukushkin says. "What if they learn from the patterns of chemotherapy treatments they receive?" He goes on to suggest that in treating cancer, it may not only be about how much of a drug is given, but also about the timing of the doses. "Just like we think about the best ways to learn efficiently, we may need to think about how to time treatments to make them more effective." This perspective opens up new possibilities for improving treatment strategies, taking into account the timing and patterns of medication in addition to dosage.