Running
Head: Neurogenesis
Neurogenesis:
A Practical Application to Humans
Thesis Paper
Kinesiology
Guelph Humber University
April 4, 2012
Gregory Roe
Neurogenesis: An Overview of Research
For
many years humans believed that the earth was square and then we decided that
the earth was round. Humans also initially believed that earth was the center
of the universe and after much deliberation we all finally agree that the earth
rotates around the Sun, which is the center of our solar system. Constantly
science has made new discoveries that have changed the outlook of our very
existence. Once again science is making a new discovery which was once believed
to be impossible; the rebuilding of damaged neurons. The concept of progenitor
cells, cells that have no distinct function, being turned into neurons is
called neurogenesis and it was believed for a long time that this phenomenon
could not occur in the brains of mammals. Through extensive research it has
been discovered that neurogenesis does occur in the brain of certain mammals,
rats being the most popular test subject.
A study done in 1965 was one of the first to
show that neurogenesis does occur in the rat brain. A Thymidine-H tracer was
given to the rats and using this tracer the proliferation of new neural cells
could be observed. This was a scientific breakthrough because it showed that
neurons can indeed be created post-natally. This opened up an entirely new
field of research into neuroscience that one day hopes to find cures for brain
illnesses. After watching the migration of cells in this study it was evident
that undifferentiated cells migrate from the lateral ventricles of the brain to
the hippocampus and more specifically the Dentate Gyrus of the brain. This
study showed that there was a 6 times increase in neurons that migrated to the
Dentate Gyrus after 3 months from birth. The study also demonstrated that there
was a higher increase in neurogenesis with rats that were given testosterone. This
study hypothesizes that hippocampal cells may act as receptors for gonadal
hormones such as testosterone. However this study did not test other hormones,
sexual and non-sexually related, which leaves other studies room to elaborate
on the subject₅. Another study done on birds showed that testosterone increased
neurogenesis as well. This
study was the first ever to show the results of testosterone on a European male
songbird. This study simply showed that there was an increase in neurogenesis
in the ventricular zone and the auditory zone of the European Sterling. This
neurogenesis was further increased with the incorporation of testosterone. This
study also showed that there was a
decline in the production of testosterone and therefore, neurogenesis with age.
This study went a little further than the previous testosterone study by
showing that testosterone increases the amount of progenitor cells that
actually become neurons in the hippocampus rather than increasing the number of
progenitor cells in total. An age related decline in proliferation of cells was
shown in this study as well. This increases the evidence of age related
decrease in neurogenesis. Why exactly this decrease occurs was not discovered
by this study. An interesting note near the end of the study shows that there
may be a correlation with the singing activity to the amount of neurogenesis. It
raises the speculation that there may be a connection between the amount of
singing or the type of singing that is done by the song birds and the amount of
neurogenesis₆.
Many different research groups have shown that
rats have neurogenic properties post natally however researchers are looking
for evidence of neurogenesis in humans. Researchers started studying the guinea
pig because the guinea pig has been shown to have a brain more closely related
to a human brain rather than a rat or mouse. This study followed the same tracing protocol as the
previous studies that have been discussed and used a Bromodeoxyuridine (BrdU)
tracer. This tracer was followed in the guinea pig and similar results were
shown compared to other neurogenic studies. There was a large increase in
neurogenesis within the first month after birth followed by a steady decline
until death of the specimen. This study decided to test the affect of glutamate
receptors on neurogenesis. The results show that there was an increase in
neurogenesis compared to the non- glutamate receptor group. This is interesting
because it seems every study is finding a new chemical that increases the
proliferation of neurons within the brain₇.
The concept of
neurogenesis in human subjects has eluded scientists for some time and due to
advancements in the scientific community an entirely new branch of human study
has opened up. Peter Eriksson was the
first person to conduct a study that showed adult neurogenesis in the human
brain. Before this study, only rodents and monkeys had shown neurogenesis in
the brain. It is believed that the
body’s inability to reproduce progenitor cells in the brain is a direct cause
of brain diseases and malfunctions. Eriksson performed research on patients who
had recently died of cancer and a BrdU radioactive tracer was used. This tracer
was followed through each of the patients and the proliferation of cancer cells
was monitored. This tracer showed that there are three distinct areas of
neurogenesis within the human brain. The Subgranular Zone (SGZ) of the Dentate Gyrus
shows the largest amount of neurogenesis. The Granular Zone shows less neurogenesis
than the SGZ but there is more neuron apoptosis in the Subgranular Zone
compared to the Granular Zone. The Hilus of the Dentate Gyrus shows the least
amount of proliferating cells however it has the least amount of cell death as
well. This also shows that progenitor
cells seem to be greatly located in the Subventricular Zone of the brain and
that these cells migrate to other parts of the brain to become different cells
based on their individual roles within the brain. Furthermore, injury and
external environmental stimulation seems to influence the rate of neurogenesis.
Unfortunately this study was unable to prove that the progenitor cells within
the Subventricular Zone (SVZ) had any function₁. Eriksson shows a graph of the
three distinct areas of proliferation and their neurogenic correlations.(See
appendix, figure 1 for graph).
California researchers
were able to show the path of the progenitor cells once they left the
Subventricular Zone. This study also used the BrdU marker to follow the cell
proliferation within the body. This
study showed that progenitor cells reside at the border of the Hilus and the
Granule Cell Layer (GCL) and travel into the Granule Cell Layer (see appendix,
figure 2). In the GCL these cells have been shown to express NeuN and
Calbindin, which are neural proliferation markers. Along with other scientist
these researchers showed that neurogenesis decreases with age in the adult
rodent. When the researchers compared the amount of neurogenesis within a 27
month old rat to that of a 6 month old rat the younger rat showed much more
cell proliferation. Along with the decrease in neurogenesis the older rats
showed an inability to react with the Polysialylated Neural Cell Adhesion
Molecule. This molecule is crucial for the migration and axon elongation of new
cells. This study shows that a decrease in neurogenesis is caused by a decrease
in Granule Cell precursors. This means
that a decrease in neurogenesis can be attributed to a lack of new cells being created
rather than cells dying. Most neurons are made prenatally. However, in mice, rats,
rabbits, guinea pigs and cats, granule cells are made post-natally. These new
Granule Cells are able to elongate their axons to the cerebellum, also known as
the mossy fiber tract. This helps in two ways. First, it allows less glucose to
be used for the cell so that glucose is not unnecessarily used. Secondly, it
allows for less synaptic junctions to be made so the brain is less congested.
This allows the brain to function better because it can have better control
over all the different neural paths₂.
Scientists
from Great Britain led by PhD Drapeau showed the age related decline in
neurogenesis in the SVZ and the Dentate Gyrus. It has been shown that in these
two areas, the decline of new neurons being formed is the greatest out of all
the neurogenic areas within the brain. (see appendix, figure 2 for a picture of
the different areas of neurogenesis). Along with the Eriksson study, these
researchers also showed that external environment had a huge effect on the
decline of new neurons being formed. Researchers have actually been able to
reactivate neurogenesis in the aging brain of humans. This proves that
neurogenesis is not simply an inevitable cell process, but a cause of an
environmental stimulation. Researchers in this study found that memory loss and
neurogenesis had a direct correlation. Based on this analysis, researchers
hypothesized that the formation of new neurons was responsible for memory
processing. It was further hypothesized that age related memory failure was due
to a decrease in neurogenesis is older populations. Interestingly enough this
article found that the aging affects the proliferation of new granule cells
rather than the absolute number. This theory is backed up by the fact that cell
apoptosis is slowed down in the Dentate Gyrus. Rodents that were studied showed
that there was a 3-4 times decrease in cell proliferation in middle aged rats
compared to young rats. Cell markers were used to determine the amount of
active precursor cells in the test subjects. What they found was that the
number of precursor cells did not change in young, middle and old aged rodents.
This may mean that aging is not correlated with the total amount of precursor
cells, but is correlated with the amount of activated precursor cells. A
decrease in the proportion of active precursor cells is associated with
age-related changes in the brain’s environment. The article goes on to say that
a potential reason that cells stop proliferating could be due to a decrease in
mitotic stimuli. This could be for two reasons. (1) The signals that increase
neurogenesis diminish in the older populations and the inhibitory signals of
neurogenesis increase with age,(2) neurogenesis can be increased by reversing
the inhibitory signals and increasing the proliferating signals. It has been
shown that neurogenesis does not increase by speeding up the cell cycle, but by
increasing the amount of precursor cells in the brain. It is interesting that
cells can stop proliferating but still retain ability to do so under the right
stimulus₃. This study concludes that more research needs to be done on age
related neurogenesis correlations however it does make some interesting
preliminary ideas₈.
Many
other research and review articles show that proliferation of new neurons
decreases with age, however a study done at a University in Germany shows the
relationship better than any other. The German researchers studied
proliferation of neurons from 0-100 years of age and found very conclusive
evidence that the studies on rats can be recreated to be done on humans as well. This group of researchers were
trying to connect the rodent brain to the human brain by finding common cell
proliferation markers. Doublecortin (DCX), one of the markers used is a marker
used in rodents that shows neurogenesis in the Dentate Gyrus of the rodent
adult brain. This same marker was used on human tissue where 54 humans were
tested positive for DCX expression from 0-100 years of age. The total amount of
cells that expressed DCX decreased over time which backs up the findings of the
above study. Along with DCX, other
markers were expressed in human tissue and some of these markers were expressed
until 100 years. This research was the first to demonstrate the link between
rodent neurogenic research and human research₄. This article showed a great
graphical interpretation of different tracers and their lifespan in the body. (See
appendix, figure 3). The researchers admit more work needs to be done on
finding a link between rodents and humans. However it was a breakthrough none
the less.
The proliferation of
cells within the brain causes new neurons to be formed within the brain, which
we have examined in this paper. However there is evidence to prove that the
brain is not the only nerve structure in the body that can be reproduced after
an injury. A study done on rats showed that, after death, the rat’s spinal
nerve cells were grown in vitro. It was hypothesized near the end of the report
that the precursor cells are derived from neuroepithelial cells located within
the rodents’ embroytic neural tube. The cells within the neural tube can replicate
into any form of nerve cell and it is believed the cells are migrated towards
the spinal cord during an injury. This study did not go into very much detail
due to the fact it was one of the first to demonstrate that spinal cord
reproduction is even possible. The researchers showed that when certain protein
expression was increased in the culture cells it would cause an increase in
neuronal cells. Neuron Specific Enolase (NSE), Neuron Specific B-Tubulin and Glial Fibrillary Acidic Protein were
given to the rats. Neuron Specific B Tubulin showed a much larger increase in
neuron proliferation compared to the Neuron Specific Enolase. The former is a
protein used to develop the exoskeleton of neurons and NSE is a protein that is
known as a Phosphopyruvate Hydratase which cleaves oxygen and carbon bonds. The
research would suggest that because an increased proliferation of the cells
given Neuron Specific B Tubulin, that it plays a more important role in the
proliferation of neuronal cells within the nervous system rather than the NSE₉.
Many different
articles have tried to show that neurogenesis is controlled by the external
environment rather than solely the internal environment. Drapeau led another
study wanting to determine if exercise, forced or from free will, would show an
increase or decrease in neurogenesis in rats. This study showed that there was
a two-fold increase in proliferating cells within the rodents that were able to
run freely on a wheel rather than being forced to remain in a confined area.
Rats were forced to do the water maze test and the Yoked swim test and the results
showed no increase in neurogenesis with this form of training. This suggests
that these tests alone are not enough to stimulate neuron growth. Other studies used treats as a positive re-enforcer;
however this study did not so that all nutrition based proliferations could be
excluded from the study. The rats were
kept in groups of three or four and showed a small increase in neural
proliferation which suggests that social interaction can be a contributing
factor to neurogenesis₁₁. Another study showed that there was an increase in
neurogenesis with the rats that got better results in the water maze test.
These researchers used the same protocol as the others with the BrdU tracing
and examined rats performing the water maze test. The rats who had a lower
latency period showed an increased number of BrdU positive cells which suggests
that there is an increased neurogenic proliferation with spatial learning. The
researchers hypothesized that the formation of new neurons is correlated to the
development of new learning and formation of memories₁₂.
A study done in 2006 does not back up these
findings but showed that rats could learn and retain information similarly with
rats that had irradiation treatment. The researchers made a control group and a
non-neurogenesis group from the rats. The control group, along with the
non-neurogenesis group were injected with BrdU tracer and a comparison of
learning was observed. One group of rodents was also given 10 minutes of gamma
radiation for two consecutive days because it had been shown to reduce
neurogenesis by 78% without any side effects. The other group was not given any
radiation. The control and irradiation rats were shocked and underwent fear
conditioning in a special chamber. The end results were that there was no
significant different between the control group and the irradiation group. The
researchers note this and refer to other researchers that found results on both
sides of the argument, one being that neurogenesis causes increased learning
and the other being that neurogenesis
does not affect all types of learning. The researchers conclude that
spatial learning has been shown to increase with neurogenesis and also state
that much more research needs to be done in the topic₁₃.
Even though there is not
a very definite link between neurogenesis and certain forms of memory retention
and learning there is a much stronger correlation between neurogenesis and
depression. Serotonin seems to be the
big neurotransmitter that is increased during anti-depressant therapy. It has
been previously shown that serotonin has neurogenic effects especially during
development of the CNS. The 5HT 1A receptor seems to play a big role in the
neurogenic effects of serotonin. D,1-fenfluramine, a drug used as an anti-depressant has been
previously shown to increase neurogenesis ₁₄.
It was also shown that activating the 5HT 1A receptors increased the
survival of new born cells. Another study showed that the depletion of
serotonin or the destruction of serotonin producing neurons caused drastic
decreases in neurogenesis. Another
article used Fluoxetine, a well known anti-depressant that increases serotonin
within the brain, and showed that there was a 70% increase in neurogenesis.
Serotonin is not the only neurotransmitter that has been shown to increase
neurogenesis. A study done on glutamate and GABA relationships in the brain
showed that GABA may be a negative feedback loop to decrease neurogenesis by
destroying DNA. Also it showed that glutamate may be a positive feedback loop
causing the increase in proliferation of cells in the SVZ. A
different article went further to say that Metabotropic Glutamate receptors
within the neurons have a direct correlation to neurogenesis. More specifically
the mGlu5 receptor was found in early life, postnatally in areas of the brain
that showed neurogenesis. The mGlu5 receptor was found in the External Granule
Layer(EGL) of the cerebellar cortex and within the SVZ. BrdU staining
successfully showed proliferation of new neurons in these regions of the brain.
This study concluded that either the mGlu5 receptor was responsible for
directly proliferating new neurons or differentiating them from progenitor
cells₁₆.
Adenosine
Triphosphate’s (ATP) also have come up in the battle for neurogenesis. This
research found that ATP was created from progenitor cells that released energy
in bursts. An increase in ATP in the brain has showed that neurogenesis
increased because an increased amount of progenitor cells differentiated into
neurons₁₇.
Along
with different neurotransmitters, stress has been shown to have an effect on
neurogenesis. One study showed that in monkeys, neurogenesis decreased. A group
of monkey’s that had either early or late stress pregnancies showed a decrease
in neurogenesis. The researchers did not find a significant difference
regarding the time of the stress during the pregnancy. The early stress monkeys
had a 21% reduction in neurogensis compared to the controls and the late stress
monkeys had a 23% reduction in neurogenesis compared to controls, using BrdU
tracing₁₈. Not all stress on the body is bad however because another article showed that exercise had a direct
correlation with increased neurogenesis in the dentate gyrus. Researchers
measured the cerebral blood volume in the brain with MRI techniques and found
that the blood volume in the brain directly correlated with cognitive and
cardiopulmonary functioning. This study showed that exercise specifically
targets the dentate gyrus which has been shown to have a direct correlation
with cognitive aging and memory₁₉.
The
brain uses fats for membrane phospholipids and it is essential in the
development and the maintenance of the brain and its functions. Docosahexaenoic acid was experimented on rats
to determine if there was a neurogenic effect on the brain due to fat
ingestion. The results showed that Docosahexaenoic acid did have a correlation
with neurogenesis in the rat brain. Researchers found that there was a decrease
in neurogenesis in the brain with a reduction of this lipid₂₆.
Lipids are not the only important nutritional requirement for
neurogenesis; it turns out that a malnourished state also halts neurogenesis.
Rats were given 4% DRI of protein (casein) (Malnurished) or 24% of DRI
(nourished). The results showed that the malnourished group had less
proliferating neurons in the brain compared to the nourished group₂₁. A very
interesting study revealed that statins may have a positive influence on
neurogenesis in the brain. The
3-hydroxy-3-methyl-glutaryl-coenzyme A (HMGCoA) reductase inhibitors have been
shown to reduce the production of cholesterol and isoprenoids, which are lipids
that regulate cell function. Statins have been shown to protect against Alzheimer’s
disease (AD) as well which affects the dentate gyrus. Statins have been
reported to increase blood flow to injured areas of the body and to increase
cerebral blood flow. After a stroke, two different types of statins were given
to rats and the results show that statins increase blood flow to the injured
area of the brain and this causes an increase in neurogenesis after a stroke₂₂.
Alzheimer’s
disease is a neurodegenerative disease where for previously unknown reasons the
neurons within the brain begin to deteriorate. It has been a long path in the
science world to discover why exactly neurons just randomly degenerate. A study
showed that the build up of B-Amyloid plaques and fibrillary tangles are one of
the causes of this form of dementia. How exactly these are formed is still a
question for scientists however. This study showed that neurogenesis does occur
in the CA1 part of the brain within the Dentate gyrus and if neurogenesis can
be increased artificially then Alzheimer’s and related diseases can potentially
be reversed₂₃. Inflammation
of the neurons and the surrounding structures within the brain, have been
reported cause for a decline in neurogenesis and a cause of AD. This study took
an inflammatory blocker, indomethacine, and gave it to rats to determine if
neurogenesis could be increased after radiation was induced. The results showed
that the inflammation was decreased and caused an increase in neurogenesis.
Patients with AD are given anti-inflammatorys as part of their regular
medication₂₇.
Many
different proteins have been studied to try and determine if any may hold the
key to increasing neurogenesis. One study showed that Reelin, an extracellular
protein that is instrumental for brain development and neuron migration that
functions through a lipoprotein receptor, may have a positive effect on
neurogenesis. It has been shown that Reelin is expressed by GABAergic neurons and
is crucial for the development of dendrites. These dendrites create new
synapses which can fix broken chains in the brain. Reelin has been shown to be
deficient in patients with AD and therefore has been linked to many
neurodegnerative diseases. This study done on mice conclude that an over
expression of Reelin can cause neurogenesis in the adult forebrain in mice by
causing progenitor cell differentiation₂₄. Many different proteins need to
still be experimented on and research is currently trying to find the links
between neurogenesis and protein structure. Hopefully one day a protein that
can be synthesized can be given to certain populations that are in need of new
neurons in their brains.
A 2005 study showed a relatively unique
concept for increasing neurogenesis in the brain. Researchers from this article
reported that lithium can be used to treat patients with neurodegenerative
diseases such as AD. Lithium is reported to be a mood stabilizer for patients
with depression and neurodegenerative diseases. It is reported that lithium
up-regulated the proteins involved in cell survival such as Brain-Derived
Neurotropic Factor (BDNF). This study showed that lithium may prevent or even
reverse neurodegeneration₃₃.
Future Research:
The world of neurogenesis has vast amounts of
possibilities that all seem to try and point to a cure for brain malfunctions.
Now knowing that neurons and supporting structures can be remade in the brain
after injury, the race is on for a legitimate cure for those who need it. Many
different brain diseases such as Alzheimer’s and other forms of dementia would
be greatly affected by a synthetic way to create neurons. Due to hippocampal
degeneration these neurologic diseases have been previously thought to be
incurable. The solution based on research may even start with the basics, a well
balanced diet. A study on patients with Alzheimer’s showed an increase in
memory when given a proper diet₂₅. (See appendix, figure 4 for graph). Not
enough humans get a well balanced diet in society due to the busy lifestyles
many lead. Europe has a mandatory 6 week-off vacation period every year and
many get more time off based on their jobs. Europeans are also healthier then
North Americans and in a recent study done comparing 14 countries it was shown
that Europeans have a higher life expectancy then Canadians and Americans₂₉. I
believe that this is because of the fact that Europeans have longer vacation
periods annually₂₈. As noted above by Coe et al., stress diminishes
neurogenesis in the brain which may be an underlying factor to why North
Americans have an increased incidence of neurodegenerative diseases₁₈,₂₉. I
have always believed that too much stress in one’s life can only do more harm
than good. I believe a mandatory day off every 4 days should be administered to
North Americans to see if there is a decrease in degenerative diseases such as
dementia. Unfortunately if people started taking more time off businesses would
face hard times having to pay more money to keep the business running. I believe
that military funding should be cut and transferred to human life expectancy
programs. Such programs would include mandatory vacations larger than the 2
weeks allowed currently. A week break every few months would be a great start I
believe. Muscles get over used during repeated use without sufficient rest so
why should we believe that the brain does not function the same way? Research
has not really answered the question as to “what happens when the brain is over
used?” .Personally I believe it will shut down and that different forms of
dementia are the bodies way of telling people it has had enough and the brain
begins to die. Stress has been shown to slow down neurogenesis and I believe
that we need to take that as a warning that North Americans need to change the
way we are living. I believe constructing time off is needed. This may include
sports, musical learning, constructive hobbies such as building models, art
etc. The brain needs to be used, like muscles in order to maintain a certain
level of functioning, however we need to be careful what we do in our spare
time. Our society revolves around
monetary values, but maybe we need to focus on well being rather than
destroying our neurons to get a new Mercedes Benz.
Neuroscience is currently working on ways to
put small electrodes in the brain that will conduct electrical signals around
the brain in manipulated ways. Some researchers are using this science to block
pain while others use it to try and increase reaction time. What if we used
electrodes to create a bridge between inactive neurons and restore brain
function? In 2002 electrodes were put
into patients with Parkinson’s disease which is a neurodegenerative disorder
like Alzheimer’s disease₃₁. Eloctrodes were put in the brain that vibrated very
fast and caused cells in the brain to be more active. The results showed that if
stimulation around 130Hz was achieved, then the patient’s involuntary
contractions would cease. If electrodes were put into the brain theoretically
that would either, (1) stimulate neurons in the brain to keep firing or
increase activity, or (2) be formed in a way that the electrodes could form a
bride between active neurons that passed inactive cells. This has not been
tested yet, however scientists do have the equipment to do this. This
suggestion does bring in an ethical issue however. Some people may argue that
surgery is very invasive and that patients should not have to go through that
procedure. I believe that if you have patients with neurodegenerative diseases
a chance to live an increased normal life, to any degree that they would agree.
If they don’t agree then nothing says they have to participate. Until a clear
electrode based solution is constructed I believe that we have an untapped human
resource for testing. Death row inmates have no rights because the government
is telling them that they do not have the right to life any more. So why not
use these inmates as experiments. If they are going to be killed anyways,
scientists should at least put their death to use. Penitentiaries could go as
far as to say that if long term inmates that are not on death row volunteer for
scientific experimentation, that time would be taken off their sentence, or if
they are a true public threat, that they get benefits in their sentence such as
extra yard time or a choice in food. Many will argue this point strongly,
however I don’t see how anyone can say they will end a life and that that falls
within moral constraints but then say that the inmates have the right to not be
to use. Why inmates have sit around and
use people’s tax money? Why not make them useful in some way?
Scientists have been struggling to find many
different supplements that may increase neurogenesis and many have been
successful in showing ways to increase the number of proliferating cells. These
methods have already been implemented into treatment processes. Scientists are
looking for a larger solution that will either stop neurogenesis all together
or restore brain function to vast degrees that has not been discovered yet. The
area of Gene modification has been shown to be a potential solution down the
road when researchers can gain a better understanding of exactly how to
manipulate genes. For example (Pattyn et al, 1997), did a study on the effects
of the Phox 2a and Phox 2b genes and their role in Neurogenesis. This study
showed that the activation or the increase of expression of these two genes
increased neurogenesis in the hindbrain. The many genes that cause neurogenesis
and diminish it have been identified through many different research projects
but recreating these genes and implementing or inactivating them still poses a
problem. Scientists do not have the equipment to be able to manipulate the
human genome in live subjects in this way. Simply, further research needs to be
done in this area because the route of all success and failures of the human
body stem from the blue print, ie. genes.
If researchers can label, recreate or
activate/ inactivate genes relating to neurogenesis then many possibilities
open up, one of them being a cure to many mental diseases like dementia. An
equally large benefit from discovering these genes is the possibility to cure
paralysis in certain subjects. Paralysis is a nerve that has been broken or disconnected
from the rest of the nervous system causing the affected area to not respond to
mental or physical stimulation. If scientists can either rebuild neurons from
the inside (neurogenesis) or create artificial bridges in the body then
potentially people can learn to regain function of lost body segments.
Unfortunately researchers are trying to fight fate because death is inevitable
and the research that is being done is simply trying to delay death. Humans are
living longer lives than previously but the root cause of death itself is still
unknown. Why exactly do humans die? Some
believe it’s the body getting tired and finally calling it quits. Some believe
it is the constant pulling of gravity on the human body and after so many years
the genes and proteins of the body, as well as its tissues simply break down.
Whatever the reason is, scientists are theoretically trying to make humans live
longer by altering genes and discovering a way to increase neurogenesis is one
of the pathways.
Appendix:
Figure 1: 
Figure 1 a graphical depiction of the number
of BrdU cells labelled in the brain after a certain amount of days- note the
decrease in numbers with increased age
Figure 2- a graphical interpretation of the areas of
high proliferation of new neurons within the brain. Note the layers of the GCL,
SGL and the Hilus. This picture shows the path of progenitor cells as noted on
page 5, par 2 ( Khun et al.)
Figure 3- life span of different
tracers in the body
Figure 4: 
Figure 4 - graph showing the effects of different macromolecule nutrition levels on
memory scores in patients with Alzeimer's Disease
References:
1)
Eriksson,
P. S. Et al. (1998). Neurogenesis in the adult human hippocampus. Nature Medicine, 4,
2) Kuhn, H. G. (1996). Neurogenesis in
the dentate gyrus of the adult rat: age-related decrease of
neuronal progenitor proliferation. Journal of Neuroscience,54(16),
145-148. Retrieved from
3) Drapeau, E., & LaNora Abrousst, D. (2007). Stem cell
review series: Role of neurogenesis in age-
related memory disorders. The
Anatomical Society of Great Britain and Ireland, 14(2), 634-638.
Retrieved from
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC29909
4) Knoth R, Singec I, Ditter M, Pantazis G,
Capetian P, et al. (2010) Murine Features of Neurogenesis in
the
Human Hippocampus across the Lifespan from 0 to 100 Years. PLoS ONE 5(1):
e8809.
doi:10.1371/journal.pone.0008809.
Retrieved from http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0008809
5)Altman, J., & Das, G. (1965).
Autoradiographic and histoloaical evidence of postnatal hippocampal
neurogenesis in rats. Journal
of Computed Neurology, 124,
319-336. Retrieved from
6) Absil, P., & , (2003). Effects of
age and testosterone on autumnal neurogenesis in male
european starling.behavioral brain research, 143(1), 15-30. Retrieved from
7) Guidi, S. (2004). Postnatal
neurogenesis in the dentate gyrus of the guinea pig. Journal of
Neuroscience, 15(3), 285-301.
Retrieved from
8) Drapeau, E.
(2008). Stem cell review series: Role of neurogenesis in age-related memory
disorders. The
Anatomical Society of Great Britain and Ireland,7(4), 569-589.
Retrieved from
9) Khel, L. (1997). Murine features of
neurogenesis in the human hippocampus across the lifespan from
0 to 100 years. Journal
of Science, 24(6),
586-589. Retrieved from
11) Praag, H. (1999). Running
increases cell proliferation and neurogenesis in the adult mouse
dentate
gyrus Neuroscience, 23(6), 266-270. Retrieved from
http://www.nature.com/neuro/journal/v2/n3/full/nn0399_266.html
12) Drapeau, E. (2003). Spatial memory
performances of aged rats in the water maze predict levels of
hippocampal neurogenesis. Albert
Einstein College of Medicine, 100(24),
14385-14390.
13 Winocur, G. (2006). Inhibition of
neurogenesis interferes with hippocampus-dependent memory
function. (16), 296-304. Retrieved from
http://www.functionalneurogenesis.com/papers/Winocur_2006_cfc_NMTS.pdf
14) Jabobs, B.(2002). Adult brain neurogenesis
and depression. Program in
Neuroscience,, (16), 602-
15) Platel, J.
(2007). Gaba and glutamate signaling: Homeostatic control of adult forebrain
neurogenesis.Departments of Neurosurgery, and Cellular and
Molecular Physiology, 38(4),
303-
311. Retrieved from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2556597/
16) Gerevini, D. (2004). The mglu5 metabotropic
glutamate receptor is expressed in zone of active
neurogenesis of the embryonic and postnatal brain. Departments of human physiology and
pharmacology in rome,150(1), 17-22. Retrieved from
17) Lin, J. (2006). Purinergic signaling
regulates neural progenitor cell expansion and
neurogenesis.National institute of health, 302(1), 356-366. Retrieved from
18) Coe, C.
(2004). Prenatal stress diminishes neurogenesis in the dentate gyrus of
juvenile rhesus
19) Periera, A. (2007). An in vivo correlate
of exercise-induced neurogenesis in the adult dentate
21) Wallingford,
J. (1980). Effect of maternal protein-calorie malnutrition on fetal rat
cerebellar
neurogenesis1.journal of nutrition, (110), 543-551.
Retrieved from
22) Chen, J.
(2003). Statins induce angiogenesis, neurogenesis, and synaptogenesis after
stroke. Journal
of Neuroscience, (53), 743-751. Retrieved from http://www.safar.pitt.edu/content/grant/jc/2005/0617
Fink.pdf
23) Jin, K.
(2003). Increased hippocampal neurogenesis in alzheimer's disease. 101(1), 343-347.
24) Pujadas, L. (2010). Reelin regulates postnatal
neurogenesis and enhances spine hypertrophy and
long-term potentiation. Journal
of Neuroscience, 30(13),
5284-09. Retrieved from
25) Kaplan, R. (2001).
Dietary protein, carbohydrate, and fat enhance memory performance in the
healthy elderly.american society of clinical nutrition, 74(5), 687-693. Retrieved from
26) Green, P. (1999). Developmental changes in
rat brain membrane lipids and fatty acids: the
preferential prenatal accumulation of docosahexaenoic acid.Journal
of lipid research, (40), 960-
27) Mcgeer, P.
(1996). Arthritis and anti-inflammatory agents as possible protective factors
for
alzheimer's disease.American journal of neurology, 47(2), 425-432. Retrieved from
28) Robine, J.
(2006). European health expectancy monitoring unit (ehemu). Retrieved from
29) Robine, J.
(2005). are we living longer, healthier lives in the eu. Retrieved from
31) Liu, X.
(2002). The oscillatory activity in the parkinsonian subthalamic nucleus
investigated using the
macro-electrodes for deep brain stimulation. Clinical neurophysiology, 113, 1-6. Retrieved from
32) Pattyn, A. (1997). Expression and interactions
of the two closely related homeobox genes phox2a
and phox2b during neurogenesis. 124, 4065-4075. Retrieved from
33) Wada, A. (2005). Lithium: Potential
therapeutics against acute brain injuries and chronic
neurodegenerative diseases. Journal
of Pharmacological Sciences,99, 307-321. Retrieved from
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