Diseases and Disorders

Adult Neurogenesis: An Overview

Hisham Ahmed


Introduction

For decades, It has been widely believed that the formation of new neurons (neurogenesis) happens only in embryonic stages during development and it stops once development ends. In 1928, the father of neuroscience Ramón y Cajal said: “the founts of growth and regeneration ... dried up irrevocably. In the adult centers, the nerve paths are something fixed, ended, and immutable. Everything must die, nothing may be regenerated” [1]. 

But in 1960 this dogma started to falter as new studies showed that neurogenesis continues to happen in the brain of some adult animals and recently they discovered that there are new signs of newly formed neurons in the adult human brain. “Can we as adults grow new neurons ?” 

There is still some confusion about that question as neurogenesis in adults is a fairly new field of research. This article contains an overview of neurogenesis, discusses what has been discovered up until now, and shows proposed points of view.

 

Overview

Adult neurogenesis is a biological process that leads to the formation of new functional neurons that integrate into existing circuits after the end of embryonic development. In most mammalians, active adult neurogenesis has been shown in two regions:

 1- subgranular zone (SGZ) in the dentate gyrus of the hippocampus

2- subventricular zone (SVZ) of the lateral ventricles, where new neurons are formed then travel through rostral migratory stream (RMS) to olfactory bulb to become interneurons [2].

These two regions are called neurogenic niches, which have molecular and cellular characteristics that make them a suitable environment for the differentiation of neural stem cells [3]. 

Neurogenesis in other brain regions and in other vertebrate classes. is believed to be very limited under normal conditions, Direct evidence of adult neurogenesis has been observed in mice, rats, song birds, and other non-human primates.

Indirect but considerable evidence of neurogenesis in adult humans also has been found [4]. The concept of adult neurogenesis in the adult human brain was introduced for the first time in 1998 when Erikson et al mentioned affirmative evidence of neurogenesis in the hippocampus after examining postmortem tissue from patients with cancer [5].

In 2013, Jonas Friesen’s lab reported that up to 700 neurons are added each day to dentate gyrus in humans [6]. Recently, there is another area that has shown evidence for adult neurogenesis in the human brain: striatum [7].

However, there is another team of researchers that has a different opinion. a big study that has been done recently by a team led by scientist Arturo Alvarez-Buylla at the University of California at San Francisco failed entirely to find any trace for young neurons in several samples of the hippocampus of adult human brains “If neurogenesis continues in adult humans, it’s extremely rare,” says Alvarez-Buylla [8]. 

 

The Seed for Adult Neurogenesis

The new neurons stand out from a population of dividing cells called neural stem cells. Neural stem cells exhibit two defining features:

1- the capacity for self-renewal through the division of the cells 

2- the capacity for forming specialized cell types through cell differentiation.  

Neural stem cells found in the brain are called multipotent due to their capability to form 2 different types of cells: 1- neurons, 2- glial cells (astrocytes, oligodendrocytes) [2].

In 1960, They were discovered for the first time by two researchers: Dr. Joseph Altman and Dr. Gopal D. Das. They were able to present evidence for the presence of neural stem cells as Altman injected adult rats with a radioactive label that gets incorporated into any newly forming DNA strands so that the new cells can be detected [9].

These findings were totally ignored and neglected by the scientific community since the radioactive label was not specific to neurons and imaging techniques couldn’t differentiate between neurons and other cell types. It also was believed that neural circuits of the brain are fixed and new neurons couldn’t be integrated into existing circuits as this will lead to disruption of brain ability to learn and remember [10]. In 1980, the world started to accept this idea when two different groups of researchers were able to isolate stem cells from the brain and show that these cells exhibit the two defining features of stem cells mentioned above [11][12]. Research continues after that to prove this dogma. For the new neurons to be fully formed, neural stem cells have to go through a process of maturation which has different steps. First, neural stem cells have to transmit from dormant state to active state and generate progenitor cells which undergo proliferation, differentiation and fate specialization to become a specialized type of cell. Then, migration happens to the place where it’s destined to settle, leading to maturation and integration to a specific neural circuit take place [13].

 

Implications

Adult neurogenesis is essential for the correct functioning of the brain. Newborn neurons have been shown to play an important role in regulating mood, memory, and spatial learning [6]. Several theoretical and computational models have been done to predict computational functions for neurogenesis in dentate gyrus which is the entry structure to the hippocampus. However, olfactory bulb hasn’t been studied extensively yet by using computational models. However, a study done by Cecchi et al.’s (2001) suggests that olfactory bulb neurogenesis will help in maximizing discrimination of odors presented to the network [14].

Some of the functions suggested by different computational models for dentate gyrus neurogenesis are as follows:

1- increase hippocampal memory capacity - several models suggested that the network capacity will increase with neurogenesis 

2- reduction of interference between new and older memories - wiskott and his colleagues propose that new neurons help the dentate gyrus to avoid the problem of catastrophic interference when adapting to new environments. They assume that old neurons are stable and preserve an optimal encoding learned for known environments while new neurons are plastic and flexible to adapt to those features that are qualitatively new in a new environment [15].

 

Is More Neurogenesis Always Better?

Recent studies show surprising limitations in the way new neurons can improve function in the adult brain. For example, In laboratory animals, dentate gyrus neurogenesis affects some hippocampal-dependent behaviors but not others. There are clearly beneficial effects on contextual fear conditioning but not on spatial learning. Animals without new neurons due to genetic ablation or irradiation perform better on certain working memory tasks. They display improved memory in radial maze but only when provided information is repeated. Thus, increasing neurogenesis may lead to an improvement in some behaviors and may have negative effects on others [16].     

 

Natural Factors and Rate Changes

Research on animals has proven that neurogenesis can be increased through natural factors. Some of the natural factors are mentioned below that may help in increasing neurogenesis in adult brains:

1- Exercise: aerobic exercise helps in increasing neurogenesis in the hippocampus and increase hippocampal volume 

2- Mental activity: working on gaining new skills (especially challenging ones) help in the survival of new neurons in the hippocampus 

3- Sleep: sleep deprivation affect the rate of neurogenesis and in chronic conditions, neurogenesis is shown to be reduced due to the increase in the level of stress hormones and on the other hand the adequate sleep help in increasing neurogenesis

4- Meditation: stress is thought to be one of the most important factors which affect the rate of neurogenesis as the decrease of physical and social stress helps in increasing neurogenesis [17].

As there are factors that help in increasing neurogenesis in adult brains, there are other natural factors that help in decreasing neurogenesis. Some of them are as follows:

1- excess alcohol consumption has a detrimental effect on generating new neurons in the adult hippocampus {18]. 

2- drug abuse such as nicotine, cocaine, and heroin has negative effects on neurogenesis and help in its suppression [19].

3- chronic stress, anxiety, and depression are associated with neuron loss in the hippocampus and a rat study has shown that stress in early life can permanently impair neurogenesis in the hippocampus. So It’s not surprising to say that antidepressants promote neurogenesis in the brain.                 

4- status also has an effect on neurogenesis as a study on songbirds’ brains showed that birds living in larger groups have more neurons and better memory than those living alone [20]. 

 

Conclusion 

The discovery of adult neurogenesis in the adult mammalian brain has ended a century-old dogma and revealed a new perspective for the plasticity in the adult brain. The concept of adult neurogenesis has been proven to exist in the adult animal brain but there is still insufficient evidence that adequately supports its presence in the adult human brain. Advancements in the neuroimaging techniques complemented with biological manipulations is still needed to provide further evidence. The understanding of adult neurogenesis starting from neural stem cells will help reveal general principles of stem cell biology, neuronal development, and plasticity. It will reveal novel insights to the function of the hippocampus and olfactory bulb and aid in developing new strategies for treatment of different neurological and psychiatric disorders.        

 

Glossary


References


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Hisham Ahmed

Hisham Ahmed


Hisham is an undergraduate student at veterinary medicine school of Cairo university. He has been a Finalist in the Egyptian national BrainBee 2018. He is very interested in using Computational neuroscience approaches to understand different neurophysiology topics. By joining IYNA he hopes to help in raising awarness about different neurological diseases and spreading neuroscience between youth. In his free time he enjoys watching movies and playing video games.