| Process of Neurogenesis |
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| The two main neurogenic niches in the brain: subventricular zone (SVZ) and subgranular zone (SGZ)[3] |
The discovery of neurogenesis in the adult brain has demonstrated that it is actually a dynamic, not static structure[1]. Adult neurogenesis primarily occurs in the dentate gyrus of the hippocampus and the subventricular zone (SVZ)[1]. The process of neurogenesis can be broken down into three steps: cell proliferation, neuronal differentiation, and cell survival[1]. During cell proliferation, neural stem progenitor cells (NPSCs), in the subgranular zone (SGZ) of the dentate gyrus, divide to produce new granule cells[1]. Some of the new daughter cells migrate outward within the granule cell layer and differentiate into neurons[1]. In cell survival, a fraction of the new neurons die while the remaining neurons mature and incorporate into the hippocampal circuitry[1]. In the SVZ, NPSCs divide to produce cells that migrate into the olfactory bulb and differentiate into olfactory neurons[2]. The rate of neurogenesis progressively declines as people age and contributes to reduced cognitive function in old age[2]. Also, our daily activities can have both positive and negative effects on the process. Neurogenesis can be increased by learning, sleep, diet, and exercise and neurogenesis is decreased by stress and certain neurodegenerative diseases. It is important to understand the mechanisms underlying the positive and negative influences on neurogenesis to develop new strategies to treat neurodegenerative diseases, repair brain damage after traumatic brain injury, and minimize the loss of cognitive function associated with aging[2].
Negative Influences on Adult Neurogenesis
main article: Negative Influences on Adult Neurogenesis
author: fabihar
| Suppresion of neurogenesis in mouse dentate Gyrus |
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| Confocal image of immature neurons in mouse dentate gyrus stained green with Doublecortin (DCX) left image: abundant numbers of DCX+ cells, right image: absence of DCX+ cells [5] |
Adult neurogenesis has been recognized as a vital life-long process in the mammalian dentate gyrus (DG) within the hippocampus[1]. Newborn neurons exhibit enhanced synaptic plasticity, increased excitability and a lower threshold for long-term potentiation compared to mature neurons[2]. These unique properties allow young hippocampal neurons to play a key role in regulating the body’s stress response and learning and memory[1]. The 3 main stages of adult neurogenesis, cell proliferation, neuronal differentiation and cell survival can be negatively regulated by stress and certain neurodiseases[1]. The neurons in the DG are densely populated with glucocorticoid receptors, and acute and chronic stress has been shown to decrease hippocampal adult neurogenesis[1]. Increased circulating glucocorticoids and cytokines have been proposed as two principal mechanisms to explain the detrimental effects of stress on neurogenesis[1]. Also, neurogenesis is reduced in neurological disorders, such as Epilepsy, Alzheimer's disease(AD) and psychiatric illnesses, like Schizophrenia[3]. New neurons fail to migrate and integrate into the DG circuitry correctly in temporal lobe epilepsy animal models[3]. While, in AD and Schizophrenia, mutations in key genes that regulate neurogenesis can completely suppress neurogenesis and contribute to the progression of the disease[4]. Animal studies have demonstrated that the consequences of decreased neurogenesis include increases in anxiety-related behaviors and impairments in cognitive function[1]. By understanding the factors that negatively regulate neurogenesis, it is possible to create treatments to rescue the neurogenic potential in patients affected by different neurological diseases and brain injuries[3].
Positive Influences on Adult Neurogenesis
main article: Positive Influences on Adult Neurogenesis
author: Pooja Chugh
| Process of Neurogenesis |
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| New born neurons start off as neuronal stem cells and transform through various stages of development before becoming granular neuron. Source: <http://www.richardsmrt.com/research?replytocom=9> |
It is often assumed that the formation of new neurons in the brain is ceased in adulthood. However, starting from birth, neurons are generated in our brains and they continue to generate throughout adulthood [1]. There are many factors that contribute to the survival of the neurons at both pre and post natal stages and that assist in further neuronal proliferation. These factors include learning, exercise, diet, and sleep. All of these things contribute to forming new neurons in the brain which in turn increases brain plasticity. Neurogenesis occurs in the dentate gyrus (DG) of the hippocampus and in the subventricular zone of the brain [2]. More specifically, neuronal cell proliferation starts in the granule cells of the dentate gyrus, then proceeds to the mossy fibres in the CA3 pyramidal neurons, before travelling through the Schaffer collaterals, and ultimately leading to the CA1 neurons [1]. The dentate gyrus is one of the only areas of the brain where neurogenesis continues to occur throughout life [3].
Neurogenesis occurs mostly in the subventricular zone (SVZ) of the brain [2]. These new born cells migrate to the olfactory bulb (sensory receptor) before developing into granule cells and integrating into the brain circuit [2]. At this time, it is unknown why this migration process occurs in humans, but the process is deemed to play a role in learning and memory [2]. Neurogenesis also heavily occurs in the dentate gyrus (DG) of the hippocampus [2]. However, these neurons from the dentate gyrus do not migrate and remain within the granule cells, even though they also play an important role in learning and memory [2]. Astrocytes are also involved in the migration of new neurons as astrocytes promote the differentiation of adult progenitor cells from the hippocampus and assist in their integration [2]. The progenitor cells that result from neurogenesis are often labelled with bromodeoxyuridine (BrdU) molecular marker to measure the level of proliferation in research studies [2].