Nuclear testing, 1955-1963, tags brain stem cells

Primate brain section showing the location of the hippocampus, by brainmaps.org/Wikimedia Commons

Neurogenesis

Neurogenesis has been demonstrated in the adult brain of several species, but the argument continues whether human brain stem cells can produce new neurons. One of the most compelling studies in favor of neurogenesis in the human brain is a 2013 multinational collaborative study by Spalding KL, et al., Cell 153:1219-1227, 2013 Cell Press (Open Access publication). This study retrospectively dated birth of neurons in human postmortem brain specimens by measuring the amount of ¹⁴Carbon present due to nuclear testing from 1955 -1963.

They concluded that the major site of neurogenesis in the human brain was the hippocampus, the part of the brain where memory formation takes place. The above illustration is a brain map of a macaque monkey displaying a dark outer band of neo-cortex.  The oldest phylogenetic area of the cortex, the hippocampus, is the circled region in the red box at the bottom of the image. The hippocampus is similarly located in the human brain. Does its shape remind you in any way of a seahorse?

An earlier 1998 qualitative study was the first to show neurogenesis in the human hippocampus. In adult mammals, the first brain stem cell population capable of developing new neurons was identified in the early 1990s in the mouse brain. In the 1998 human study, postmortem histology of a cancer patient’s brain confirmed the presence of neurons created after initiation of chemotherapy to treat the cancer. The drug used against the cancer was only able to incorporate into the nuclear DNA of newly formed cells. Neurons possessing the drug marker in their DNA were only observed in the patient’s hippocampus. There was no indication of new neuron formation during the treatment in other brain structures.

Quantifying new neurons of brain

Above-ground nuclear testing significantly increased the amount of ¹⁴Carbon, a radioactive form of carbon, present in the atmosphere. Before nuclear testing there were only trace amount of ¹⁴Carbon in Earth’s atmosphere, about 1part ¹⁴Carbon per trillion non-radioactive ¹²Carbon molecules. The natural occurrence of ¹⁴Carbon in the atmosphere is a result of comic ray action upon nitrogen gas.

¹⁴Carbon in the air reacts with oxygen to form ¹⁴CO₂. Plants cannot distinguish ¹⁴CO₂ from ¹²CO₂. Since the nuclear testing period, ¹⁴CO₂ has been incorporated into plant glucose to a greater extent than it was before 1955. Plants being the primary food source for man and animals, ¹⁴Carbon is now distributed throughout human bodies. And some of the excess ¹⁴Carbon from nuclear testing became incorporated into the DNA of cells created after 1955.

Spalding et al. used several mathematical models to estimate the rate of new neuron formation, neurogenesis, based upon ¹⁴Carbon in DNA of neuron cell populations from various areas of the brain.

As ¹⁴Carbon decays to ¹²Carbon, it emits a low energy beta particle that can be detected. The half-life of the decay process for ¹⁴Carbon is 5,730 +/- 40 years. That is, after about 5,700 years half of the original material will have become ¹²Carbon. The level of ¹⁴Carbon measured in the postmortem DNA was compared to the amount of ¹⁴Carbon in plants before 1955. Tree rings are a good source of plant levels before 1955.

With these methods Spalding et al. concluded that a sub population of adult human hippocampus neurons, corresponding to most of the dentate gyrus neurons, possess an annual turnover rate of 1.75%. This corresponds to 700 new neurons added daily in each hippocampus, right and left hemisphere.

Based upon the oldest subject in the study investigators also concluded that the new neurons develop in the adult human brain at least into the 5th decade of life. And, they only found a modest decline in new neuron formation during normal aging.

Hippocampus manages memory formation

Episodic memory formation recalls specific events of a person’s life. It is the long-term memory that people worry most about losing with age and disease. A special part of episodic memory is a person’s memory of those events that make up their own life’s history.

The hippocampus region of the brain is where new episodic memories begin. And, it is the only place in the human brain where birth of new neurons has been confirmed in the adult. Episodic memory formation is a complex process. Often new episodic memories incorporate parts of old memories. For example, if you revisit your old school for a reunion, memory of the reunion will incorporate earlier events from the past when you attended classes at the school.

Continual incorporation of new neurons into the brain pathways that support memory adds a new perspective to the theories about the brain’s infrastructure for memory. It is accepted that the hippocampus orchestrates storage of the the details of previous memories and is critical for their recall.

But, the various particulars of long-term episodic memory such as color, place, sound etc. are not stored in the hippocampus. Rather they are stored as bits and pieces in various parts of the outer layer of cells covering the brain, the cerebral cortex. There are very active incoming and outgoing neural pathways between the hippocampus and the cerebral cortex that are used to bring the details of previous events back for incorporation into new memories.

Neural stem cells and episodic memory

In the 2013 study of neurogenesis in the adult human brain, the half-life of dentate gyrus new neurons was 7.1 years. This is ten times shorter than the half-life of the non-renewing neurons of the rest of the hippocampus. Studies of the characteristics of new dentate gyrus neurons in rodents suggest, at least in those animals, that young neurons have a greater capacity for creating new synapses for connection to other neurons.

Other studies demonstrate that episodic memory formation is also associated with increased synapse creation. Theories propose, therefore, that the birth of new neurons may be required for efficient episodic memory management. Current thought is that new dentate gyrus neurons may be required for the ability to store similar experiences as distinctly different events. Another theory is that the non-renewing neurons of the remainder of the hippocampus are necessary to associate similar memories with each other.

It will require more study and new methods, or creative use of existing opportunities, to confirm or deny the current ideas about the importance of new adult neurons of the brain to the infrastructure of episodic memory formation. However prevalent neurogenesis in memory formation in laboratory animals, animal data must be reconfirmed in humans before it is accepted for humans.

For a more in depth description of how the cells of the human brain work together, take a look inside my book “Inside the Closed World of the Brain” by clicking here.

Further reading:

Human Memory Formation& Recall

Brain’s Memory Circuits

Do you have questions?

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Margaret Thompson Reece PhD, physiologist, former Senior Scientist and Laboratory Director at academic medical centers in California, New York and Massachusetts is now Manager at Reece Biomedical Consulting LLC.

She taught physiology for over 30 years to undergraduate and graduate students, at two- and four-year colleges, in the classroom and in the research laboratory. Her books “Physiology: Custom-Designed Chemistry”, “Inside the Closed World of the Brain”, and her online course “30-Day Challenge: Craft Your Plan for Learning Physiology”, and “Busy Student’s Anatomy & Physiology Study Journal” are created for those planning a career in healthcare. More about her books is available at https://www.amazon.com/author/margaretreece. You may contact Dr. Reece at DrReece@MedicalScienceNavigator.com, or on LinkedIn.

Dr. Reece offers a free 30 minute “how-to-get-started” phone conference to students struggling with human anatomy and physiology. Schedule an appointment by email at DrReece@MedicalScienceNavigator.com.