The Mechanism of "Pruning" in the Human Brain
- From: James Michael Howard <jmhoward@xxxxxxxxxxxxxxxx>
- Date: Sat, 25 Mar 2006 12:55:45 -0500 (EST)
The Mechanism of ?Pruning? in the Human Brain
Copyright 2006, James Michael Howard, Fayetteville, Arkansas, U.S.A.
The development of the human brain is rapid following birth, reaching about
95 percent of its size by age five to six. The large growth of a baby?s
brain results from an ?over-abundance? of neurons and synapses. These
begin to decline around age three; some of the neurons and synapses are
?pruned.? The remaining neurons and synapses are enhanced by this process.
Another period of enhanced synapse formation occurs just prior to puberty
in children in the prefrontal cortex. This is followed by another period
of pruning during adolescence. (The foregoing is a compilation of the work
of Dr. Jay Giedd, et al., at the National Institute of Mental Health.)
I wish to suggest a mechanism to explain these findings. It is my
hypothesis that mammals evolved because of selection for DHEA ( Hormones in
Mammalian Evolution, Rivista di Biologia / Biology Forum 2001; 94:
177-184). I think primates evolved from mammals because of selection for
testosterone within the mammals (ibid, 2002; 95: 319-326). A continuance
of selection for testosterone within the primates resulted in humans
(Androgens in Human Evolution, Rivista di Biologia / Biology Forum 2001;
94:345-362). I suggest the interaction of these two hormones may explain
the enhanced brain of humans as well as the mechanism of ?pruning.?
It is my primary hypothesis that DHEA optimizes replication and
transcription of DNA. Therefore, DHEA will positively affect all tissues.
The increases of testosterone during evolution of primates and humans
positively affected the ability of some tissues, more than others, to
absorb DHEA. I think the most important of these is the brain. This is
why the brains of primates and humans are increased in size compared to
other mammals. Testosterone stimulates formation of the ?androgen
receptor? in tissues. DHEA utilizes the androgen receptor.
DHEA is known to ?have positive effects on hippocampal CA1 spine synapse
density in both sexes (Endocrinology 2004; 145: 4154-61). DHEA ?increases
the number of newly formed cells [neurons]? even in adult rats (Eur J
Neurosci 2002; 16: 445-53). DHEA promotes neuronal survival following
anoxia (Brain Res 2000; 871: 104-12) and ?may participate in protecting the
integrity of synaptic membranes against hyperglycaemia-induced damage?
(Biochem Pharmacol 2000; 60: 389-95). Other work ??suggest that DHEA is
involved in the maintenance and division of human neural stem cells.? (Proc
Natl Acad Sci USA 2004; 101: 3202-7). Testosterone is known to positively
affect the brain in some circumstances, not all. I suggest sufficient DHEA
must be available to exert ?positive? effects of testosterone in these
cases.
DHEA is highest at birth. This is followed by a rapid decline during the
first year of life reaching very low levels. DHEA again begins to increase
around age three to five, though it is often ?defined? somewhat later (J
Clin Endocrinol Metab 2005; 90: 2015-21). I suggest the ?decline? in DHEA
is caused by absorption of DHEA by the brain for growth and development at
this time. The fetal brain is exposed to maternal testosterone in utero.
This induces androgen receptor formation which is used to absorb DHEA for
growth and development of the brain. I suggest the rapid growth of a
baby?s brain is caused by the large amount of DHEA available at birth.
Neurons and synapses growth rapidly and luxuriantly because of this DHEA.
DHEA is used by the brain at the expense of the rest of the body so DHEA
levels decline and other tissues do not develop as rapidly. This is why
the brain of babies develop rapidly and their bodies do not. As the brain
finalizes its growth and development, the body begins to use increasingly
available DHEA for growth and development. This use of DHEA by the body
begins to compete with the brain. Neurons that are being activated
continue to absorb DHEA readily; neurons that are not activated do not
continue to absorb DHEA so they, and their synapses, decline. This may
explain the ?pruning? that begins around age three as the body begins to
compete for DHEA with the brain.
I suggest all growth and development rely on DHEA. The exposure to
testosterone, in male and female fetuses, triggers formation of androgen
receptors. These receptors increase the use of DHEA. Hence, testosterone
first activates receptors that allow absorption of DHEA. This stimulates
growth and development of the brain. Prior to puberty, testosterone, in
males and females, again increases. I suggest this exposure to
testosterone, again, promotes growth and development of the brain first
followed by the body.
The prepubertal testosterone stimulates the final part of brain formation
in humans, the prefrontal lobes, to occur. That is, this part of the brain
is stimulated to produce androgen receptors in the prefrontal lobes which
begin to absorb DHEA. This results in growth of this part of the brain
just prior to puberty. This use of DHEA is, again, at the expense of the
body. Hence, there is a reduction in growth of the body just prior to
puberty. When the growth of the prefrontal cortex is finished, then DHEA
is, again, freed for use by the body and the body starts the ?adolescent
growth spurt.? This competition for DHEA reduces growth and development of
the prefrontal cortex except the areas absorbing sufficient DHEA to remain
functional. Therefore, this is a period, again, of ?pruning? of neurons
and synapses that do not absorb sufficient DHEA.
This may also explain why neurons do not increase with age in people.
Since DHEA naturally begins to decline around age twenty and testosterone
does not resurge, even declines, neurons are not affected by increased
androgen receptors and little DHEA is available for absorption and use by
neurons.
Testosterone and sufficient DHEA stimulate neuronal growth. Growth, use of
DHEA, reduces further growth. Use of DHEA by other tissues reduces
maintenace of neurons so pruning of ?least-used? neurons occurs.
.
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