What is Neurogenesis?

Neurogenesis is the process by which new neurons are formed in the brain through pre-natal development and as adults. This phenomenon primarily occurs in the hippocampus  playing a crucial role in learning, memory, and cognitive flexibility. Factors like exercise, enriched environments, and certain drugs can promote neurogenesis, while stress and aging may inhibit it.

Neurogenesis was traditionally believed to only occur during embryonic development, which is now understood not to be the case.

The human brain comprises billions of cells, including neurons, glia, and an undetermined number of subtypes. During the very early stages of development, in embryonic stages, most of these cells are generated.

Early neurogenesis begins with separating the neural plate from the ectoderm (the outermost germ layer during early embryonic development) by folding to form what is known as a neural groove.

This then fuses to form the neural tube, which is the precursor to the central nervous system (CNS), and the neural crest, a temporary group of cells. The neural crest will then produce neural crest stem cells, which then become multiple different cell types, contributing to the development of tissues and organs.

The diversity of neurons in the brain is a result of neurogenesis during embryonic development, making this process especially crucial during development.

During neurogenesis, the neural stem cells differentiate, meaning they will become one of a number of specialized cell types at specific times and regions within the brain.

Adult neurogenesis

It was believed that neurogenesis in humans only occurred during embryonic development. The brain’s cells and their circuits were thought to be fixed, with the only changes occurring when there was a loss of cells and a reduction in brain volume.

It was found in many species of animals that there was evidence of self-repair and continued growth of neurons. However, mammalian brains were thought to be an exception to this.

It was understood that other cells, such as microglia, astrocytes, and oligodendrocytes were able to divide in adults and respond to injury. Despite these cells being able to divide, only the neurons were considered to not be able to replicate themselves.

It is now understood that this limitation on neurons is not true, and adult neurogenesis can occur.

Back in the 1960s, neurogenesis in adults was said to be discovered.

Altman and Das (1965) pioneered studies during this decade and provided the first anatomical evidence for the presence of newly developed neurons in adult rats’ hippocampus.

Likewise, Paton and Nottebohm (1984) later found functional integration of newly developed neurons in the central nervous systems of songbirds.

Despite evidence since the 1960s that adult neurogenesis exists, it took until the 1990s for the field as a whole to accept that neurogenesis in adults has a role to play in brain function. Richards, Kilpatrick, & Bartlett (1992) were fundamental researchers to the realization of this discovery.

These researchers discovered that there were neural stem cells in the brains of adult mice. As neural stem cells are required for neurogenesis, it was concluded that this process can occur in mammalian brains.

Significant advancements have been made since this discovery of neural stem cells in mammals in almost every aspect of adult neurogenesis in the mammalian CNS. It has been discovered that adult neurogenesis may be restricted to only two brain regions: the subgranular zone (SGZ) and the subventricular zone (SVZ).

The SGZ in located in the dentate gyrus of the hippocampus, which has been revealed to be the area where new dentate granule cells (small cells important for learning) are generated.

Whereas the SVZ is located in the lateral ventricles, which is a region where new neurons are generated, and then they migrate to the olfactory bulb (an area involved in the sense of smell) in order to become interneurons (Kempermann & Gage, 2000).

How neurogenesis occurs

Neurogenesis is a complex process involving several stages, primarily taking place in the dentate gyrus of the h in adult mammals.

Neurogenesis in the brain starts by getting triggered by neurogenic signals. These could arise from several factors, such as stimulated activity in certain brain regions. This then helps to develop and stimulate neural stem cells.

These stem cells with then either divide indefinitely to produce more stem cells, or they will differentiate to give rise to neural progenitor cells. Neural progenitor cells are a stage between stem cells and fully formed neurons.

At this stage, the neural progenitor cells also differentiate to develop specific types of neurons. Likewise, glial cells, which have supportive functions in the CNS, are triggered by gliogenic signals to help stimulate neural stem cells.

The neural stem cells with gliogenic signals will then become glial progenitors, which differentiate into support cells such as astrocytes and oligodendrocytes.

This process is known as gliogenesis, rather than neurogenesis.

Neurons within mammals’ CNS have been shown to originate from three classes of stem and progenitor cells: neuroepithelial cells, radial glial cells, and basal progenitors.

The onset of neurogenesis transforms the neuroepithelial cells into radial glial cells, which are responsible for producing all the neurons in the CNS, including supportive cells – astrocytes and oligodendrocytes.

hippocampal neurogenesis

As previously mentioned, neurogenesis in adult mammals has been discovered to occur in two main areas: the subgranular zone (SGZ) of the dentate gyrus of the hippocampus and the subventricular zone (SVZ) situated throughout the lateral ventricles of the brain.

The hippocampus is part of the limbic system and is located deep within the temporal lobes of humans. This region is a vital part of the brain, essential for laying down new memories, recall, and learning.

Astrocyte cells within the dendrite gyrus of the hippocampus produce the proteins that trigger the process of neurogenesis. The role of neurogenesis in the dendrite gyrus helps it to encode new information.

In animal experiments, neurogenesis in this region is measured by injecting their brains with a radioactive marker that attaches itself to dividing cells. Counting the marked cells when the animal dies shows exactly how many cells have multiplied.

The rate of adult-born neurons within the hippocampus is around 700 per day. Approximately one-third of the neurons within the hippocampus are replaced in a person’s lifetime as a result.

Adult neurogenesis in the hippocampus is thought to play a crucial role in regulating mood, spatial memory, and the allowance of new memories to be stored.

The creation of new brain cells in the hippocampus can however disrupt the existing memories located in this area.

Most memories are formed in the hippocampus and are then transferred to long-term storage elsewhere. For some time, the memories exist in both the hippocampus and other brain regions for a few years until the memory is cleared from the hippocampus.

Until the pre-existing memories are fully transferred, the arrival of new cells may weaken the memories already stored there. This may be a reason why we cannot retain all of our memories from when we were young.

Neurogenesis within the SVZ of the lateral ventricles eventually gets transferred to the olfactory bulb. The olfactory bulb is a structure located near the front of the brain in both cerebral hemispheres, which receives neural input about odors.

If new cells were prevented from developing in the SVZ, this could negatively impact cognitive function, including olfactory memory.

Aside from the SVZ and SGZ, more recently, researchers have shown that adult neurogenesis can occur in the amygdala, a brain region important for processing emotional memories.

More research is required into this area, but this could be a way in which new emotional memories are formed.

Why is neurogenesis important?

Since stem cells can divide and differentiate into many types of cells, the discovery of neurogenesis in the human adult brain implies that this could be key for the treatment of neurodegenerative conditions such as Alzheimer’s disease.

Currently, there is no cure for Alzheimer’s disease. However, neuroscientists are now interested in developing methods in which to use the brain’s stem cells and progenitor cells to enhance neurogenesis in the hippocampus.

If they are successful in increasing the production of new neurons in this area, they may be able to treat these neurodegenerative conditions, as well as possibly age-associated memory and cognitive decline, and mental illness.

There is often cross-talk between neurogenesis and synaptic plasticity, known as a change in activity during synaptic transmission. Synaptic plasticity is a neurophysiological correlate of learning and constitutes the ability for the reorganization and adaption of the brain in response to the changing environment.

In rodents, it has been found that after experiencing a stroke or seizure, the brain can produce new cells in order to repair itself. Thus, there was enhanced neurogenesis as a result of damage.

This has implications for therapeutic methods of brain repair after experiencing brain damage. Recently, scientists are investigating methods to activate dormant stem cells in the event that the areas where neurons are located become damaged.

Other researchers are seeking a way of transplanting stem cells directly into damaged areas to encourage them to repair the damage. Similarly, researchers are seeking to take stem cells from other sources, such as from embryos, to influence these cells to develop into neurons or glia cells.

Finally, methods to stimulate the amygdala into producing new brain cells could have the potential to treat disorders associated with fear, such as anxiety, posttraumatic stress disorder, and depression.

What causes neurogenesis to increase and decrease?

The main cause of a decline in neurogenesis is aging. The natural degeneration of the brain is not caused by disease and, therefore, cannot be avoided.

Research has shown that despite this, most neurons actually remain healthy until death, but brain size can decrease by around 5-10% from the age of 20-90.

It is also suggested that lifestyle factors such as increased blood glucose levels from foods, a lack of exercise, and sleep deprivation can all cause a decrease in neurogenesis.

A decrease in neurogenesis has also been associated with mental health conditions such as depression, anxiety, and post-traumatic stress disorder.

In contrast, it has been suggested that exercise can increase neurogenesis in the dentate gyrus, resulting in more new neurons being produced. Adult neurogenesis can also be stimulated by social interaction, learning, and a healthy diet.

Essentially, it is considered that activities that can stimulate the brain in a positive way help in the production of new cells. Finally, it has been found that antidepressant drugs and electroconvulsive therapy are other methods of increasing neurogenesis.

References

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