Neurogenesis (birth of neurons) is the process by which neurons are generated. Most active during pre-natal development, neurogenesis is responsible for populating the growing brain.
New neurons are continually born throughout adulthood in predominantly two regions of the brain:
- The subventricular zone (SVZ) lining the lateral ventricles, where the new cells migrate to the olfactory bulb via the rostral migratory stream
- The subgranular zone (SGZ), part of the dentate gyrus of hippocampus.
Many of the newborn cells die shortly after they are born,
but a number of them become functionally integrated into the surrounding
Adult neurogenesis is a recent example of a long-held
scientific theory being overturned, with the first evidence of mammalian
neurogenesis presented in 1992.
Early neuroanatomists, including
Santiago Ramon y Cajal, considered the nervous system fixed and
incapable of regeneration. For many years afterward, only a handful of
biologists (including Joseph Altman, Shirley Bayer, and Michael Kaplan)
considered adult neurogenesis a possibility.
In 1983, with the
characterization of neurogenesis in birds and the use of confocal
microscopy, the possibility of mammalian neurogenesis became more
apparent, but it was not until the early 1990s that hippocampal
neurogenesis was demonstrated in non-human primates and humans.
recently, neurogenesis in the cerebellum of adult rabbits has also been
Further, some authors (particularly Elizabeth Gould) have
suggested that adult neurogenesis may also occur in regions within the
brain not generally associated with neurogenesis including the
However, others have questioned the scientific evidence of
these findings, arguing that the new cells may be of glial origin.
Neurogenesis and learning
The functional relevance of adult neurogenesis is uncertain,
but there is some evidence that hippocampal adult neurogenesis is
important for learning and memory.
Multiple mechanisms for the
relationship between increased neurogenesis and improved cognition have
been suggested, including computational theories to demonstrate that new
neurons increase memory capacity, reduce interference between memories,
or add information about time to memories.
Experiments aimed at
ablating neurogenesis have proven inconclusive, but several studies have
proposed neurogenic-dependence in some types of learning. and others
seeing no effect Studies have demonstrated that the act of learning
itself is associated with increased neuronal survival.
overall findings that adult neurogenesis is important for any kind of
learning are equivocal.
Neurogenesis and stress
Adult-born neurons appear to have a role in the regulation
Studies have linked neurogenesis to the beneficial actions of
specific antidepressants, suggesting a connection between decreased
hippocampal neurogenesis and depression.
In a subsequent paper,
scientists demonstrated that the behavioral benefits of antidepressant
administration in mice is reversed when neurogenesis is prevented with
In fact, new-born neurons are more excitable
than older neurons due to a differential expression of GABA receptors.
plausible model, therefore, is that these neurons augment the role of
the hippocampus in the negative feedback mechanism of the HPA-axis
(physiological stress) and perhaps in inhibiting the amygdala (the
region of brain responsible for fearful responses to stimuli).
consistent with numerous findings linking stress-relieving activities
(learning, exposure to a new yet benign environment, and exercise) to
increased levels of neurogenesis, as well as the observation that
animals exposed to physiological stress (cortisol) or psychological
stress (e.g. isolation) show markedly decreased levels of new-born
Some studies have hypothesized that learning and memory are
linked to depression, and that neurogenesis may promote neuroplasticity.
One study proposes that mood may be regulated, at a base level, by
plasticity, and thus ''not chemistry''. Accordingly, the effects of
antidepressant treatment would only be secondary to change in
Effect of sleep reduction and stress levels on neurogenesis
One study has linked lack of sleep to a reduction in rodent
hippocampal neurogenesis. The proposed mechanism for the observed
decrease was increased levels of glucocorticoids.
It was shown that two
weeks of sleep deprivation acted as a neurogenesis-inhibitor, which was
reversed after return of normal sleep and even shifted to a temporary
increase in normal cell proliferation.
Neurogenesis and Parkinson’s disease
Parkinson’s disease is a neurodegenerative disorder
characterized by a progressive loss of dopaminergic neurons in the
Transplantation of fetal dopaminergic
precursor cells has paved the way for the possibility of a cell
replacement therapy that could ameliorate clinical symptoms in affected
patients. Experimental depletion of dopamine in rodents
decreases precursor cell proliferation in both the subependymal zone and
the subgranular zone. Proliferation is restored completely by a
selective agonist of D2-like (D2L) receptors.
A detailed understanding of the factors governing adult
neural stem cells ''in vivo'' may ultimately lead to elegant cell
therapies for neurodegenerative disorders such as Parkinson’s disease by
mobilizing autologous endogenous neural stem cells to replace
This occurs through activation of dopamine
receptors in these areas which produces glutamate release and subsequent
elevation of local basic fibroblast growth factor (bFGF)
concentrations. The consequences of these actions are potentiated reward
responses and therefore increased drug cravings and consumption which
underlie abuse and addiction.
Whether these mechanisms could be
exploited for the purpose of enhancing basal hedonic tone is unknown.
Neurogenesis and exercise
Scientists have shown that physical activity in the form of
voluntary exercise results in an increase in the number of newborn
neurons in the hippocampus of aging mice.
The same study demonstrates
an enhancement in learning of the "runner" (physically active) mice.
While the association between exercise-mediated neurogenesis and
enhancement of learning remains unclear, this study clearly demonstrates
the benefits of physical activity and could have strong implications in
the fields of aging and/or Alzheimer's disease.
Neurogenesis and old age/Alzheimer's disease
Allopregnanolone, a neurosteroid aids the continued
neurogenesis in the brain. Levels of allopregnanolone in the brain
decline in old age and Alzheimer's disease.
Allopregnanolone has been
shown through reversing impairment of neurogenesis to reverse the
cognitive deficits in a mouse model of Alzheimer's disease.
Regulation Of Neurogenesis
Many factors may affect the rate of hippocampal neurogenesis. Exercise
and an enriched environment have been shown to promote the survival of
neurons and successful integration newborn cells into the existing
Another factor is central nervous system injury since
neurogenesis occurs after cerebral ischemia, epileptic seizures, and
bacterial meningitis. On the other hand, conditions such as chronic
stress and aging can result in a decreased neuronal proliferation.
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