Can We Regenerate Brain Cells?

Can We Regenerate Brain Cells?
Neurons releasing chemical neurotransmitters at the synapse (Eraxion/thinkstockphotos.com)
Marina Zhang
7/24/2022
Updated:
10/5/2023
0:00

For many decades, neurologists and medical students were taught that neurogenesis, the formation of new brain cells, does not happen in the adult brain.

It was believed that when cells in other organs died they were replaced with fresh new ones whereas the brain was seen as a special organ where once neurons died, they were lost forever.

This belief came from the words of Santiago Ramon y Cajal, who was known as the father of modern neuroscience.

Cajal wrote in 1928 that “once the development was ended, the founts of growth and regeneration…dried up irrevocably. In the adult centers, the nerve paths are…fixed, ended…everything may die, nothing may be regenerated.”

However from the 1960s to 90s, neurologists could no longer dismiss contradicting research that showed evidence of neurogenesis in adulthood.

The concept of adult neurogenesis was therefore established as a field of research.

Nevertheless, over 30 years later, scientists are still uncertain if brains can really regenerate nerve cells, and the research remains controversial.

Most research findings support the concept of neurogenesis, while others do not.

Neurogenesis, a Controversial Research Field

Is neurogenesis real?

For Dr. Orly Lazarov from the University of Illinois at Chicago, who has over 20 years of research in this field, the answer is yes.

“I would say that there’s a lot of evidence that suggests that neurogenesis does exist,” Lazarov told The Epoch Times in a phone call.

Her team’s research found evidence of neurogenesis in the hippocampus (memory center) in very old individuals, including those that were in their 70’s to 90’s.

They studied postmortem brain tissue from 18 individuals aged 79 to 99 years, 10 of whom had Alzheimer’s disease.

The team found that hippocampal tissues collected from 17 of the 18 samples had protein markers that are common to proliferating neurons and 14 samples also had markers for neural stem cells (Sox2+).

Neural stem cells are progenitor brain cells and can differentiate into various types of brain cells, including neurons. Therefore finding markers for them in the brain suggests possible neural generation.

Some of the brain tissues also contained markers common to already differentiated, but still immature neurons, suggesting that there may have been cells in the older individuals that were recently generated.

Despite evidence of neurogenesis, the researchers noted that individuals who are old and suffering from cognitive diseases had significantly reduced markers for brain cell formation compared to brain tissues collected from younger individuals.

“Human neurogenesis declines with age and aging, [but] it does exist, for a life in a human brain,” Lazarov said.

However, Lazarov’s findings can be contested, and this is why this field of science is so contentious. Though her studies focused on markers mostly present in young progenitor neurons, in rare cases, these markers can be present in mature neurons and may not be direct evidence of neurogenesis.
Further a 2022 study examining the genes activated in neurons from different species found that genes related to neurogenesis were activated in the hippocampus in adult mice, monkeys, and pigs, but this activation was negligible in humans.

Genetic activation associated with cell proliferation and differentiation was detected in only one human cell.

Nonetheless, other studies that suggest adult neurogenesis have found that in the human amygdala (emotion center), lipofuscin, a pigment that accumulates in aging neurons, was not present in over 3 percent of the neurons.

This suggests that around 3 percent of neurons were likely to be younger than the individual, indicating generation of new neurons over a lifetime.

As a developing field, research on brain regeneration remains controversial, however the scientific evidence is increasingly leaning towards acknowledgement of neurogenesis.
Young family with children having fun in nature (Lucky Business/ShutterStock)

Neurogenesis in Children Versus Adults

Throughout life, we go through two stages of neurogenesis.

The first stage is in the embryo where all the neurons we will need in our life are formed. This includes neurons in the brain, spinal cord, and in the muscles.

These neurons are responsible not just for learning, memory, and motor skills, but also involuntary and voluntary movements such as breathing, postures, sensations, and circulation, among many other functions.

At the time of birth, babies are born with double the number of neurons than that of an adult. Emerging studies speculate that new brain cells are being formed in the first years of life although at a rapidly declining rate.

In the first few years of life, neurons formed in the embryo will gradually be pruned and fine-tuned as babies learn their first words, take their first steps, and learn different activities.

Neurons deemed necessary will be strengthened and lengthened, and will form more connection points with other neurons. On the other hand, cells that are deemed unnecessary will be weakened and killed off.

The literature generally suggests that the brain fully matures at around 25 to 26 years of age.

By the age of 6, the volume of gray matter (neurons) will have peaked, and by 28 to 29 years of age, the volume of white matter (myelin sheath which wraps around and insulates neurons) will peak.

The brain will start to shrink somewhere between the 30’s and 40’s. This shrinking is accelerated when people enter their 60’s.

While the neurogenesis in the embryo forms the infrastructure of neurons that will gradually mature into a brain, studies on adult neurogenesis suggest that the neurons formed in adulthood are mostly related to learning, memory and mood.
Current literature shows that the regions for neurogenesis are the lateral subventricular zone, the dentate gyrus in the hippocampus, and the amygdala, though cells that are capable of neurogenesis have also been found elsewhere. 

Lazarov’s studies mostly focused on the hippocampus, a seahorse structure deep in the brain. The structure is very important in memory formation as well as mood regulation.

She found that brain cell generation in the dentate gyrus of the hippocampus may be crucial for memory and spatial navigation.

When she stimulated a neural death gene in mice, she found that mice lost recognition memory, such that they lose their ability to recognize previous events and objects, easily verified through a lack of a fear response to fear conditioning.
Her other experiments showed that removing neurogenesis by stimulating neural death caused mice to lose their ability for spatial memory (enables you to navigate your way around the city), recognition memory (knowing to avoid the same step that you tripped on yesterday), pattern recognition (picking out your bike out of many bikes in a shed), and associative memory (knowing that chocolate is brown and has a sweet taste).

What Brain Cell Regeneration Means For the Brain

Research on neurogenesis suggests that brain cell generation may be preventative for both brain and neuronal disorders.
Lazarov’s previous study on mice predisposed to Alzheimer’s found that placing the mice in enriched environments with a lot of stimuli increased neurogenesis and reduced hippocampal neuronal loss.

Mice in enriched environments formed more neurons compared to mice with the same genetic disposition in less enriched environments. These mice also had a reduced onset of hallmark for Alzheimer’s disease as they aged, with lower beta-amyloid protein accumulation (hallmark of Alzheimer’s).

Lazarov’s most recent study on rodents found that previously “lost” memories can be retrieved once neurogenesis is enhanced.

For example, a mouse may have known its way around a certain structure, but since the development of Alzheimer’s-like symptoms, it has “lost” that memory.

However, when Lazarov’s team stimulated neurogenesis, the memory was “rescued” and returned to the mouse.

This is because when new neurons are made, they will be recruited into specific networks that participate in storage of a previously formed memory.

Therefore, neurogenesis may be able to help retrieve a “lost” memory that is still present, just somehow inaccessible.

“We’ve shown that the deficiency of new neurons in Alzheimer’s disease at least in part plays a major role in memory deficits and as soon as the number of new neurons is augmented, we’re able to rescue the memory,” Lazarov said.

“New neurons participate in the group of neurons that is critical for the storage of new memories…because the level of neurons in Alzheimer’s disease is reduced in the hippocampus, this could be one mechanism by which memory are…not being…stored properly and then maybe also not being able to be retrieved well.”

However, apart from preventing memory loss common to old age, other studies have shown that neurogenesis may also be linked with improvements in mood.

Reduced neurogenesis have been linked with depression and increased anxiety in mice.

Memory loss comes hand in hand with the aging process, therefore neurogenesis may be able to slow down the aging of the brain.

Lazarov said that in the future, her team may be able to develop a medication that can increase neurogenesis. People can take it even before they show disease symptoms in order to delay the onset of disease.

Currently, some scientists have found a molecule called brain derived neurotrophic factor (BDNF), which is a protein in the brain and spinal cord. This protein promotes the survival of neurons by contributing to neural growth, maturation, and maintenance linked to increased proliferation of neurons and also possible to the generation of new neurons.
People whose blood contained the highest amounts of three key antioxidants were less likely to develop all-cause dementia than those whose blood had lower levels of these nutrients. (ShutterStock)

How to Increase  Neurogenesis

Dr. Lazarov’s medication is still far from being developed, so in the meantime there are always natural ways worth considering to help boost brain vitality and wellbeing.
  • Sleep

A restful good night’s sleep promotes and boosts neurogenesis, allows neurons to reorganize and form new networks. Good sleep also aids in the clearing of waste from the brain. Though restricting sleep for one day may have little affect on neuronal proliferation rate, studies on rats show that restricting sleep in the long-term is linked to reduced neurogenesis. Too much sleep is also not recommended as studies on prolonged sleep suggest that too much sleep can also reduce cognitive abilities and decision-making. A healthy adult needs around 7 to 9 hours of restful sleep. Babies, children, and teenagers need longer.
  • Exercise

Exercises have been shown to increase BDNF proteins in rats, especially high intensity exercise at intervals.
Studies in mice have shown that short-interval anerobic exercise increased BDNF levels and neurogenesis. Another study in human patients with metabolic syndrome also found that high-intensity exercises in intervals, coupled with a low-carbohydrate and a Paleolithic-based diet (diet high in lean meats, fish, fruits, vegetables, nuts and seeds) improved cognition.
  • Intermittent Fasting

Mice studies have shown that fasting for at least 12 hours increased markers for neurogenesis in the hippocampus. Fasting increases the release of human growth hormones. These hormones reduce inflammation and promote autophagy (cleaning and removal of wastes), which favor cellular repair and neuroprotection. In human studies, fasting in patients with brain-related disorders can reduce amyloid precursor proteins in mild cognitive impairment and improve overall cognitive functioning. Intermittent fasting has also been shown to lessen the frequency and severity of seizures in epilepsy.
  • Nutrition

Omega-3 fatty acids, polyphenols (anthocyanins, curcumin, cabalamin (Vitamin B12), and Vitamin E have all been documented  (pdf) in the scientific literature to be neuroprotective and to reduce neuronal damage. Omega-3 fatty acids and cobalamin (commonly obtained through fish and meat) are anti-inflammatory and are necessary for the formation of new neurons and neurotransmitters, respectively. Anthocyanin (found in blueberries) is an antioxidant that prevents cellular injury in neurons. Curcumin, obtained from turmeric, has been shown to reduce beta-amyloid plaques that are the hallmark of Alzheimer’s disease.
  • Learning

Learning something new increases brain plasticity, the ability for the brain to organize itself and form new networks and connection points between neurons. Studies on taxi drivers have shown that taxi drivers have a larger hippocampal volume than non-drivers, and learning a musical instrument has been linked with improved brain plasticity due to the learning requires to modulate between the brain’s visual and sensory regions.
  • Positive emotions

Positive feelings may also increase neurogenesis. Studies on rats found that rats that were tickled (positive emotion) for 5 minutes everyday had increased neurogenesis compared to rats that did not. Hormones that are associated with positive emotions such as oxytocin (love hormone) and endorphins (an euphoric and pain-relieving hormone often released during pain and exercise) have been shown to increase and modulate neurogenesis in mice.
Screentime, processed foods, antibiotics, environmental toxins, and psychiatric drugs have all been linked to obesity. (zhang tianle/Shutterstock)

What Decreases Neurogenesis

  • Drugs

Long-term consumption of drugs such as alcohol, heroin, amphetamines, marijuana, opioids, and cocaine can cause neurological damage. Long-term users of drugs have changes in brain morphology, often including reduced gray matter volume in the prefrontal cortex. The use of these drugs has also been linked with acute memory loss acute in the short term and memory deficits in the long-term. Rat studies have shown that exposure to drugs reduced neurogenesis in their hippocampus as well as loss of short-term memory.
  • Processed Foods

Studies on refined sugar, additives such as monosodium glutamate (MSG), aspartame, and trans unsaturated fats suggest that these additives may impair brain functioning. Sugar hyperactivates neurons and overconsumption has been linked with cognitive deficits in mice. MSG and aspartame are excitotoxins, meaning that they can overstimulate the neurons in the brain and cause injury or subsequent death of neurons. Trans unsaturated fats can cause inflammation, leading to neuronal stress and damage, and have been linked with memory loss.
  • Overeating

Obesity has been long linked with reduced cognitive function, however researchers found that the habit of overconsumption may be the actually culprit behind cognitive decline. Studies on overconsuming mice found these mice had smaller hippocampal volume indicative of reduced neurogenesis.
  • Sedentary and Unstimulating Lifestyle

If exercise increases neurogenesis, then it is likely that the opposite reduces it. Non-activity in mice reduced markers for neuronal growth in the brain. Studies in humans showed that sitting for long periods was associated with thinning of the brain’s medial lobe, an area critical to memory formation. Likewise children who spend longer periods of time viewing screen media have been found to have reduced development in brain white matter associated with literacy and language skills.
  • Negative emotions

Negative emotions, such as feelings of depression, reduce the plasticity of neurons. Studies have shown that depressed individuals have lower neurotrophic factors responsible for promoting the survival and growth of new neurons. Brains of people with depression often have impairment in neuronal connections, as well as reduced hippocampal volume.
Marina Zhang is a health writer for The Epoch Times, based in New York. She mainly covers stories on COVID-19 and the healthcare system and has a bachelors in biomedicine from The University of Melbourne. Contact her at [email protected].
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