Visit the Principles of Psychobiology home page for details about our innovative software for students in the brain sciences.
Link
to this Page (HTML code, instructions, etc.)
Tell
a Friend about this site
Test
Your "Brainpower"
Brain
models, books and videos and more...
|
|
|
|
| Recommended books | |
Are
Mood Disorders Strictly Related to a Neurochemical "Imbalance"?
(Probably
Not...)
Neuroscientists have found a severe depletion of cells in the brains of
people who died with depressive illness. The finding is the among
the first pieces of physical evidence which confirms that depression and
manic depression may be triggered by a specific abnormality in the organization
of brain cells. The unusual finding is that this abnormal organization
of brain cells relates to glial cells (Module
1; Principles of Psychobiology), not neurons.
Dr. Wayne Drevets and colleagues, researchers at the University
of Pittsburgh, studied brain tissue from seven people that were diagnosed
with either depression or manic depression, and found that anywhere from
40 to 90 percent of glial cells were missing in the region examined.
The area of the brain analyzed was within the prefrontal cortex (Module
5; Principles of Psychobiology), called the anterior cingulate
cortex. In 1996, Drevets reported that there was a significant decrease
in blood flow in this region of the neocortex in living patients with manic
depression and depression.
The frontal neocortex and anterior cingulate gyrus has been associated
with emotional processing, specifically how a person decides whether a
certain behavior, thought, or feeling, will be rewarding. People
with mania, for instance, can be impulsive. One theory is that they
don't know what effect their behavior may have on themselves or others.
In addition to establishing a support network for neurons and blood vessels,
and acting to encapsulate and degrade foreign and abnormal material in
brain tissue, glial cells provide a transport system for specific
ions (Module 1-2; Principles of Psychobiology)
that are important in neuronal signaling, specifically potassium (K(+)).
Drevets said that he and his colleagues were surprised when they found
that these depressive conditions may be associated with an abnormally low
number of glial cells. In research, glial cells have taken a back
seat to neurons.
The study was done in collaboration with then doctoral student Dost Ongur
and Professor Joseph L. Price of the Department of Anatomy
and Neurobiology at Washington University, St. Louis.
"We weren't even going to count the glial cells because we thought that
the neurons themselves would be down in number," Ongur said. "We
were stunned," Drevets added. "We think this is the single most important
finding in mood disorders."
Drevets also suspects that glial cell loss contributes to the loss of brain
volume noted on brain scans, causing an abnormality in the brain's ability
to process emotions.
| Recommended books | |
More Attempts at Treating Parkinson's Disease; The Plot Thickens...
Parkinson's disease involves a loss of both dopamine-containing neurons
in substantia nigra, and axons of the nigrostriatal pathway (Modules
5 & 6; Principles of Psychobiology). Patients afflicted
by this disease exhibit problems in both voluntary and involuntary motor
movement, and symptoms can include tremors, rigid limbs and inability to
move.
Various attempts have been made to circumvent functional loss that accompanies
Parkinson's disease. In many people with advanced Parkinsonism,
treatment with levodopa (l-dopa; precursor to dopamine neurotransmitter
production; Module 6; Principles of Psychobiology)
has been initiated in an attempt to elevate levels of dopamine released
by surviving dopamine projection systems. However, l-dopa helps only
some patients some of the time.
Experimental methods have been attempted to circumvent the symptoms of
Parkinson's disease. One attempt has been direct electrical stimulation
of the substantia nigra, which provided equivocal results.
The basal ganglia include a group of forebrain structures that are all
known to be involved in movement functions. The substantia nigra,
as well as other structures, are included in the basal ganglia. Interconnections
between these structures, and other structures such as the thalamus and
cerebellum, establish a so-called "motor loop" (Module
5; Principles of Psychobiology). Therefore, it may
be possible that functional losses associated with degeneration of the
nigrostriatal system could be offset by altering another component of the
"motor loop".
Electrical stimulation of another component of the basal ganglia has been
shown to greatly improve the ability of Parkinson's disease patients to
perform motor responses. Patricia Limousin of Grenoble
University and colleagues found that electrical stimulation of the
subthalamic nucleus caused a 60 percent improvement in patient's motor
skills ability. These results are reported in the New
England Journal of Medicine.
When l-dopa therapy was used, electrical stimulation improved symptoms
slightly and helped decrease the jerky movements that are a side
effect of the drug. The average dosage of l-dopa was cut in half, and other
drugs were also reduced or eliminated. These results further reinforce
the notion that many brain "systems" work in parallel to provide complex
behavioral functions.
| Recommended books | |
Adult Human Brain Cells May Have More Than One Birthday
It is widely believed that adult human brain cells do not regenerate.
Most textbooks state that humans are born with as many neurons
as they will ever have, and that as we progress through life we may lose
many of these original neurons. A recent study may seriously challenge
this information.
A study by Peter S. Ericksson and colleagues at the Sahlgrenska
University Hospital in Goteborg, Sweden, indicates that neurons in
the hippocampus of adult humans may undergo what is known as neurogenesis.
These results are to be published in the November 1 issue of the journal
Nature
Medicine.
Ericksson and colleagues utilized techniques acquired while visiting the
Salk
Institute's Professor Fred H. Gage, who participated in the study.
The study employed tissue from terminal cancer patients who had undergone
a diagnostic procedure that labels cells which are in the process of dividing
or replicating. In this procedure bromodeoxyuridine (BrdU) is delivered
to patients by injection, and the nucleic acids of cells which are dividing
incorporate the BrdU. Later, the BrdU is visualized by the use of
immunohistological methods (Module 6; Principles
of Psychobiology), by using an antibody to BrdU. Only cells
that are in the process of dividing will incorporate BrdU, and the BrdU
labeling therefore serves as a "birthday marker" for newly formed cells.
Dr. Gage, discussed these results in an interview with National
Public Radio© (NPR) (REAL AUDIO(tm) INTERVIEW). UniSci Science
and Research News also quoted Dr. Gage as stating that "All of the patients
showed evidence of recent cell division." He also added that "It's
interesting to note that this was not a particularly young or healthy group
of people, so new cell growth may usually be even more prominent that we
observed."
Evidence of neurogenesis has been gathering for years in infrahuman species,
and this study is very important because it shows that human brain cells
may, indeed, have the ability to replicate. It is now important to
determine whether or not these regenerating cells establish appropriate
connections in the brain, or whether they merely replicate and then die,
without establishing connections. This line of investigation has
obvious implications for clinical attempts to circumvent functional loss
that results from CNS damage.
| Recommended books | |
Brain Implants That Allow "Willful Thinking"
Neuroscientists have implanted a device in the motor neocortex of two people
that has allowed them to operate a computer display by "thinking" about
it. It has been known for many years that direct electrical stimulation
of particular brain regions can elicit sensory experiences, memory recall,
or motor responses. However, unlike scenes from many (oftentimes
bad) science fiction movies, it has always been unclear whether or not
brain cell activity could be used to control external machines.
Dr. Phillip R. Kennedy, a researcher who has worked with researchers at
Georgia
Institute of Technology and
Emory
University, developed an implant that can be used to detect that activity
of neurons, and convey these signals to computers for further processing
and control operations. The small recording sensor is enclosed in
a glass envelope and coated with nerve growth factors that allow neurons
in the region of the implant to establish functional connections with the
sensor. Normally, when recording electrodes are implanted in brain
tissue the region surrounding the electrode is enveloped by glial cells
(Module
1; Principles of Psychobiology) that attempt to encapsulate
the "foreign" material. This electrically isolates the recording
electrodes from small amplitude potentials that are conveyed by individual
axons, dendrites or gap junctions (Modules 1-5;
Principles
of Psychobiology). The key development is the application
of nerve growth factors that apparently encourages the growth of functional
connections to the recording electrode -- This formation of intact connections
could be followed after implantation by a change in the pattern of electrical
activity detected by the electrode.
Surgeries on two patients were performed by Dr. Roy Bakay from Emory, who
presented the findings at the Congress
of Neurological Surgeons annual meeting in Seattle. The electrodes
were implanted in the motor cortex, near the arm/facial region (Module
7c; Principles of Psychobiology), and signals were routed to
a computer that moved a cursor across a screen to an icon region.
Both patients were paralyzed and unable to move their limbs or speak.
The first patient, who had the implant for 2.5 months before dying from
amyotrophic lateral sclerosis, learned to control the signals in
an "on-off manner" for seven days. The second patient (J.R.), who
suffered brain stem stroke after a heart attack, has had the implant for
6 months. Initially, this patient had a problem stopping his brain's
electrical activity, but researchers programmed a pause into the system
so that whenever the cursor landed on an icon, it stopped. Eventually,
the patient was able to stop the cursor at an icon and click it to say
a word or a phrase.
"This will hopefully open up a whole new world for J.R.," Bakay said.
"He is learning and so are we."
More
on this development from National Public Radio...
Click
Here For NPR© Link (REAL AUDIO (tm) INTERVIEW)
| Recommended books | |
Serotonin...The Master Mood Modulator...
People who suffer from anorexia/bulimia may be born differences in brain
chemistry that makes them prone to eating disorders. It has been
known for many years that the brains of adult bulimics contain abnormal
levels of the classical neurotransmitter serotonin (5-HT) (Module
6; Principles of Psychobiology), a neurotransmitter that influences
mood states, obsessive-compulsive behaviors, and aggression.
It has not been known whether these abnormal levels of 5-HT relate to the
eating disorder, or whether 5-HT levels are abnormal prior to the
onset of the eating disorder. A recent study by Dr. Walter Kaye,
professor of psychiatry at the Western
Psychiatric Institute in Pittsburgh, suggests that serotonin levels
may be abnormal before adult bulimics begin the cycle of bingeing and purging.
The study compared 31 healthy women with 30 women who once suffered from
bulimia but had returned to normal eating habits for at least a year.
Serotonin levels were measured in spinal fluid, and Kaye found that recovered
bulimics had abnormally high levels of serotonin. Also, recovered bulimics
showed many of the symptoms associated with high levels of serotonin, including
negative moods and obsessions. Because all of the women in the study had
resumed healthy eating habits, the findings indicate that diet, alone,
cannot account for the altered serotonin found in individuals who are exhibiting
bulimia. Instead, high serotonin levels may be a genetic condition that
leaves some people prone to the disorder, Kaye said. Previous studies of
twins of bulimics and anorexics also have indicated that the eating disorders
may be genetic, "so there's accumulating evidence here."
Women with high serotonin levels may be prone to eating disorders in part
because the elevated serotonin levels tend to make them depressed, anxious
or obsessed with control, and starvation can lower the level of serotonin.
Serotonin is a product of tryptophan, which comes from amino acids in food.
"Their abnormal eating habits make them feel temporarily better," Kaye
said.
But the serotonin levels may then drop below normal, which can cause feelings
of impulsiveness, disorder and anxiety, so the bulimic person may binge
to bring the serotonin back up again. "They start to chase something
they never really can catch," Kaye said.
More
on serotonin systems and suicide from National Public Radio...
Click
Here For NPR© Link (REAL AUDIO (tm) INTERVIEW)
| Recommended books | |
Alzheimer's Disease: The Wicked Web...
Background
from National Public Radio (1997)
Click
Here for NPR© Link (REAL AUDIO (tm) INTERVIEW)
It now seems that a relatively harmless protein in the brain is somehow
induced to cause damage to neurons when it changes molecular shape. As
it undergoes this change, the protein called amyloid beta begins forming
abnormal strand-like structures that accumulate on neurons. The accumulation
of amyloid beta then appears to induce another normal protein, called Tau,
to form aggregates that eventually kill brain cells.
The two proteins distribute abnormally in individuals with Alzheimer's
disease (Module 5; Neocortex; Principles of
Psychobiology), forming the "plaques and tangles" that have characterized
the disease since it was first described in 1907 by Alois Alzheimer. However,
until recently, scientists have not known how or why these proteins are
involved in the disease, there has been no general consensus on the reasons
that plaques and tangles are produced in Alzheimer's disease.
Three studies published in the July 1997 issue of Nature
Medicine added additional insight into these questions. To place
the significance of these results in perspective, it is important to understand
that researchers have been divided into two "camps" for the past 15-20
years. Amyloid substance has been visualized in neurons of Alzheimer's
patients for many, many years. Thus, it was suggested that amyloid protein
may build up excessively in cells during Alzheimer's disease. Other researchers
suggested that a so-called Tau protein, similar to cytoskeletal
proteins (Module 1; Principles of Psychobiology),
forms abnormal cytoplasmic aggregates in neurons called "tangles", which
eventually kill the cell.
As is usually the case in science, it appears that both camps are right...
Bruce Yankner and
colleagues at Children's Hospital
in Boston studied the brains of primates, which are genetically related
to humans, and exhibit similar responses to brain disease. Yankner took
the same amount of amyloid beta found in a human brain "plaques" and injected
it into the brains of an aged rhesus monkey, a young rhesus monkey
and aging marmoset monkeys, which are genetically different from rhesus
monkeys. Yankner found that injections of amyloid beta into the brain of
aged rhesus monkeys caused the same damage found in the brains of people
with Alzheimer's disease. It also caused changes in Tau protein, which
appeared to begin forming tangles. The brain of the young rhesus
monkey did not respond to the injection of amyloid beta, and the brains
of aged marmosets were only slightly affected.
The young rhesus monkey was apparently protected from developing plaques.
This experimental observation is interesting because, on average, symptoms
of Alzheimer's disease do not manifest until individuals are 60-65 years
of age.
A second study conducted by Claudio Soto of the New
York University Medical Center. provides dramatic evidence that a drug
may be developed to block amyloid protein from becoming harmful. The study
also shows it may be possible to dissolve the plaques on brain cells after
they have formed.
Soto and colleagues conducted experiments with live rats and human cultured
cells. They created a synthetic agent that binds to a part of the amyloid
protein that is involved in the twisting and folding that occurs when normal
amyloid changes to become toxic. When delivered to rats, the compound completely
blocked the induction of plaques by injected amyloid. Moreover, the synthetic
compound dissolved plaques on human brain cells that were grown in culture--it
was as if the synthetic compound "unwound" the plaque. The synthetic agent
is a peptide made up of only five amino acids.
Finally, researchers at the Institute
for Physical Biology in Dusseldorf, Germany, have developed a technique
for diagnosing altered forms of amyloid in spinal fluid of patients with
Alzheimer's disease. This method employs fluorescence correlation
spectroscopy to detect very small aggregations of amyloid in patients with
the disease. The test detected these aggregations with nearly 100% accuracy.
We still are not sure
what induces the development of altered amyloid protein, but the studies
mentioned above begin to give us ways to possibly slow, or eliminate, the
progression of the disease.
| Recommended books | |
Establishing Functional Connections Following Spinal Cord Damage...There May be Hope...
Researchers at Purdue University have
apparently confirmed that it is possible to "fuse" axons of the spinal
cord that have been severed by trauma. By performing studies on isolated
spinal cords derived from guinea pigs the researchers have, for the first
time, recorded electrical potentials from a previously severed spinal
cord axons. Not all of the axons were experimentally repaired following
damage, but the fact that some axons were repaired is a great step
forward. "If you have even 5 percent of the nerve fibers carrying
nerve impulses, you'll get significantly more than 5 percent back in terms
of restored behavior," says Richard B. Borgens. He and his colleague, assistant
professor Dr. Riyi Shi, both of Purdue's
Center for Paralysis Research in the School of Veterinary Medicine,
will report their findings today in Long Beach, Calif., at the 18th annual
meeting of the Society for Physical Regulation in Biology and Medicine.
Borgens also has submitted a paper on the research to the Journal
of Neurotrauma.
For many years researchers have known that certain chemicals, such as polyethylene
glycol (PEG), have the ability to fuse lipid membranes. In fact,
PEG is used in the now-common technique of monoclonal antibody production
to fuse different antibody-producing cells together. In their spinal
cord studies, Dr. Borgens used a similar approach to fuse cut axons
of the spinal cord. Obviously, it is not possible to re-establish
the original connections, but connections are established. Electrical
impulses were restored in all of the guinea pig cords used in the study.
The repaired spinal cords transmitted between 5 percent and 58 percent
of pre-cut impulses.
Borgens and Shi applied polyethylene glycol, or PEG -- a nontoxic, water-soluble
polymer used in medicine and cosmetics -- across the region of the
guinea pig's spinal cord that had been severed but gently pressed back
together. PEG was applied for two minutes, then removed. The polymer "fused"
the membranes of a significant number of axons, apparently establishing
physical connectivity with regions above and below the cut..
Using an apparatus and procedure that Shi designed, the researchers then
applied a small electrical current to one end of the cord to stimulate
nerve impulses to travel towards the other end (Module
3; Principles of Psychobiology). Between five and 15 minutes
after the PEG application, nerve fibers were repaired, allowing some impulses
to reach the other end of the severed cord in 100 percent of the cases.
The authors also confirmed connectivity by the use of tract-tracing techniques
(Module5: Principles of Psychobiology)
Unisci News quoted the authors as stating that: "In most spinal cord injuries
in animals and in people, the spinal cord is not completely severed, as
we have done in these first experiments," he says. "The cord is more likely
to be crushed, and the nerve fibers develop holes in their membranes, which
ultimately leads to separation of the nerve fiber within 24 to 72 hours."
The PEG method may allow trauma care facilities to "plug-up" damaged membranes
before neural degeneration begins.
Borgens and his colleagues have done extensive work in producing other
methods to treat naturally paralyzed dogs with spinal cord injuries, and
some methods have moved to testing phases in human spinal cord injuries.
| Recommended books | |
Some
Background (12/96) about the Memory of Mice with "Holes in Their Heads"...
Click
Here For NPR© Link (REAL AUDIO (tm) INTERVIEW)
The
Hippocampus and Cabbie's Brains
For many years, the hippocampus has been implicated in spatial memory functions in animals (Module 5; Principles of Psychobiology). For instance, animals that have received experimental damage to the hippocampus exhibit problems utilizing spatial stimuli during learning tasks and/or they cannot remember spatial "maps" (such as maze routes) as well as normal animals. The hippocampus in humans appears to function similarly. National Public Radio conducted an interview in November 1997 with an investigator who used a cleaver method to investigate this spatial function in humans.
More
on the Human Hippocampus from National Public Radio...
Click
Here For NPR© Link (REAL AUDIO (tm) INTERVIEW)
| Recommended books | |
Biological Basis for Dyslexia (?)
Dyslexia is a disorder in which individuals appear to process written words,
and acoustical (mental) representations of written words, much differently
that normal individuals. For instance, dyslexics oftentimes have
trouble learning words and reading. They may have trouble rhyming words,
may mix up letters such as "d'' and ''b'', and may have trouble spelling
-- despite often above-average intelligence and motivation.
Dyslexia tends to run in families, suggesting that there is a genetic basis
for the symptoms. There are no firm figures on
the incidence of dyslexia in the population, but 10 to 15 percent of school
children have learning disorders, and 80 to 85 percent of them have language
and reading based problems. The International Dyslexia Association
suggests that a large proportion of such problems may relate to dyslexia.
Researchers have found differences in the way that information is processed
in the brains of dyslexics. Dr. Sally Shaywitz of Yale University and colleagues
used magnetic resonance imaging (MRI) to study the brains of 32 normal
volunteers and 29 dyslexic adults. The individuals in the study were
asked to take a series of reading tasks.
Shaywitz's team found that non-dyslexic people increased their brain activity
as reading tasks got harder, while dyslexics did not. When the dyslexics
read, Shaywitz's MRIs recorded a pattern of under-activation in a large
area at the back of the brain associated with language. In
particular, they found the angular gyrus, which is considered key to the
visual and language skills needed for reading, was disrupted in the dyslexics.
Wernicke's area, which is nearby and important to language comprehension,
was also under-activated in dyslexics.
``These findings have important implications for the large numbers of intelligent
men, women and children with dyslexia,'' the researchers, who reported
their findings in the Proceedings of the National Academy of Sciences,
said in a statement. ``If you have a broken arm
you can hold up an X-ray as evidence. Up to now, individuals with dyslexia
were often doubted and there was little concrete evidence they could show
to support the neurobiologic nature of their reading difficulty.''
Previously, British researchers reported that they had found three
common genes associated with dyslexia in blood samples from 90 families.
You
will need Quicktime® to view this movie
View
Quicktime Movie from Philadelphia Newspapers Inc. about results from studies
of Dyslexia
More
on Dyslexia from National Public Radio...
Click
Here For NPR© Link (REAL AUDIO (tm) INTERVIEW 03/02/98)
| Recommended books | |
The Paradox of Sleep
We spend
roughly 30% of our lives in sleep, and one of the most fascinating questions
in the neurosciences has been "Why do we sleep, and what brain mechanisms
cause sleep." These are valid questions for the neurosciences, because
certain brain injuries and abnormalities can dramatically alter the wake-sleep
cycle (Module 5: Principles of Psychobiology)
(see below).
Although several theories have advanced to explain the why of sleep,
it is generally believed that sleep serves to aid in some form of restorative
function. Key data that support these theories are related to the
observation that sleep deprivation causes adverse physiological changes
in animals and humans, sometimes resulting in death.
Many of the classical neurotransmitters have been implicated in sleep.
It is generally thought that "excitatory" and "inhibitory" transmitters
somehow interact to modify particular wake-sleep states. Moreover,
there may be a control mechanism of some sort that affects how particular
transmitters function to produce wake-sleep states.
In early 1996 an interesting hypothesis was presented which suggests that
sleep does serve a restorative function with regard to energy restoration
in brain cells. Specifically, it is proposed that low levels of extracellular
glucose trigger the release of the nucleotide adenosine, which then may
serve to inhibit several of the "excitatory" neurotransmitter receptors.
During this process, glycogen stores in astrocytes (glial cells: Module
1: Principles of Psychobiology) also may be converted to glucose,
thereby restoring extracellular energy reserves for neurons. This
proposal was presented by J.H.
Benington and H.C. Heller in Progress in Neurobiology, and NPR
conducted an interview with Dr. Heller, of Stanford University about
the energy-restoration hypothesis.
More
on this Hypothesis from National Public Radio...
Click
Here For NPR© Link (REAL AUDIO (tm) INTERVIEW)
What about the where of sleep in the brain? The reticular (activating) system, Raphe' nuclei, locus coeruleus, and hippocampus have been implicated as brain structures that regulate sleep (Module 5: Principles of Psychobiology). In 1996, J.E. Sherin, P.J. Shiromani, R.W. McCarley, and C.B. Saper presented data in Science which may implicate a critical brain region that serves as a "switch" to control the activity of many of the aforementioned nuclei. Not surprisingly, this potential "sleep switch" may be located in the hypothalamus, together with other control centers for vital body functions.
More
on a Potential "Sleep Switch" from Phillynews
Click
Here for the Link to Phillynews Archives
| Recommended books | |
Lithium
and Bipolar Disorders
Nearly 50 years ago, Australian psychiatrist John F. Cade demonstrated
that lithium ions exert a mood-stabilizing effect on individuals
with manic-depressive symptoms (bipolar disorder). It has been estimated
that approximately 2.5 million Americans may be afflicted with a bipolar
disorder. Since Cade's early observations, lithium has been termed
a "wonder drug" in clinical treatment. However, while it is generally
assumed that that lithium somehow affects the CNS in individuals with bipolar
disorders, the way in which lithium operates to stabilize mood swings has
remained elusive. Researchers have new clues in the puzzle of how lithium
can effectively stabilize bipolar disorders.
A study reported in the July
7, 1998 Proceedings of the National Academy of Sciences found
that, in mice, lithium exerts a push/pull effect on the synaptic levels
of glutamate, eventually causing it to stabilize at a level where it can
control both mood extremes. University of Wisconsin Medical School
professor of pharmacology, Dr. Lowell Hokin, directed the research.
Glutamate is the primary excitatory neurotransmitter in the brain (Module
6; Principles of Psychobiology), and it has been estimated that
approximately 85 percent of neurons in the brain either release glutamate
OR are receptive to glutamate. Other neurotransmitters include serotonin,
dopamine, norepinephrine and acetylcholine, but the glutamate system is
extremely widespread in the brains of all organisms. Normally, presynaptic
potentials cause a release of glutamate which interacts with receptors
postsynaptically. Re-uptake transporters located presynaptically then reabsorb
some of the glutamate, pumping it back into the cell for reuse (Module
6; Principles of Psychobiology).
If the reuptake mechanism malfunctions, inappropriate concentrations of
glutamate can remain in the synapse. Hokin postulates that abnormally low
glutamate levels are involved in depression, while high levels are
responsible for mania.
In an earlier study (reported
in PNAS, Aug. 30, 1994), Hokin and colleague showed that lithium
causes glutamate to accumulate in synapses of mice and monkey brain slices,
but exactly how it worked remained unclear. In the current study, functioning
slices of mice brain were examined following exposure to lithium, while
control slices were not exposed to the drug. The researchers observed that
lithium raised the synaptic glutamate level by slowing its reuptake. The
higher the lithium dose, the greater the accumulation of glutamate.
Clinically, it takes a while for lithium to exert its effects on bipolar
disorders. To experimentally study the chronic effect of the lithium,
the UW team administered it to live mice for two weeks. To their surprise,
they saw that glutamate reuptake increased. This "up-regulation" of transporters
resulted in a lowering of synaptic glutamate, which would produce an anti-manic
effect. "We were especially interested to find that the reuptake mechanism
in the 18 lithium-treated mice was stabilized in a very narrow range, as
compared to the 18 controls," he said.
Hokin proposes that a compensatory mechanism in the reuptake system
strives, over time, to stabilize synaptic glutamate in a fixed range.
When the levels of glutamate are too low, as postulated in depression,
lithium may elevate synaptic glutamate.
The research findings support clinical observations, he noted. "It takes
a few weeks before lithium begins to relieve depression and mania in bipolar
patients," he said. "It's now apparent an adaptive reuptake mechanism that
brings glutamate within a 'normal' range works over time to curb both the
highs and lows." Moreover, he added, lithium doesn't change
the moods of people who aren't bipolar, suggesting that their glutamate
levels may be positioned consistently within the set zone, and therefore
would not be affected by the drug.
| Recommended books | |
More About Microbes and Alzheimer's Disease
For about 15 years researchers that have examined the brains of Alzheimer's
patients have noticed something very unusual. In addition to the
characteristic neuronal anomalies that characterize Alzheimer's disease,
such as "plaques and tangles", investigators have been seeing what appears
to be both bacterial and viral fragments in areas of the brain that have
degenerated. This has given rise to one hypothesis that Alzheimer's
disease may have an infectious basis. In fact, a correlation has
already been established between late-onset Alzheimer's and infection with
herpes simplex virus type 1.
One group of neuroscientists recently identified a specific bacterium
in the brains of Alzheimer's patients, and these results were presented
at the 1998 annual meeting of the Society for Neuroscience.
These investigators examined brain tissue of Alzheimer's patients after
autopsy and found that a bacterium called Chlamydia pneumoniae had
invaded brain cells in regions where Alzheimer's damage was detected.
Researchers were surprised to find the presence of the bacterium because
it normally cannot cross the blood-brain barrier, and in Alzheimer's patients
it appeared to have traveled far beyond its common entry point into the
body, the sinuses and lungs.
The finding is important to "our potential understanding of how an infectious
agent could lead to the neurodegeneration observed in Alzheimer's disease,"
according to Brian J. Balin, of Allegheny
University of the Health Sciences in Philadelphia.
Rather then observing what was suspected of being bacteria, Balin and colleagues
analyzed DNA segments from the putative bacteria. The bacterium type
was confirmed in post-mortem brain samples of 17 of the 19 Alzheimer's
patients he analyzed. Conversely, 18 of 19 brain samples from people that
died of other causes showed no signs of the organism.
"At this time, we do not know if the presence of this organism is causative
or if it is a risk factor for the disease," Balin wrote. "However, we believe
that our findings support those of others suggesting that inflammation,
which can be stimulated by this bacterial infection, is a very important
aspect of late-onset Alzheimer's disease." When cells become
infected with the bacterium, the cells produce chemicals to fight the infection.
Some of these inflammatory chemicals, called cytokines, can damage nerve
cells.
This suggestion has good face validity because it has recently been reported
that patients taking over-the-counter anti-inflammatory compounds, such
as aspirin and ibuprofen, show a slower rate of disease progression.
Zaven Khachaturian, a consultant to the Alzheimer's Association,
said the critical question is to identify the trigger, which he suggested
might be some sort of trauma or other incident that creates damage to the
blood-brain barrier and lets the bacteria in. "Now you have a break in
the pipe...setting the stage for other events to occur. I think this is
a likely scenario."
Khachaturian said it's also important to find out whether the bacteria
has set the stage for Alzheimer's in the patients who died, or whether
the Alzheimer's damaged the brain, letting in the bacteria.
Interestingly, the same bacterium has been detected in the fatty plaques
that clog heart arteries, though researchers do not yet know if it is responsible
for the clogging.
| Recommended books | |
Brain Circuits and Hallucinations
Neuroscientists have caught a glimpse of what appears to be brain circuits
that are unusually active during schizophrenic hallucinations, where
patients hear voices and see things that aren't there. The observations
may help researchers understand why some individuals "hear" or "see" something
that is not "real".
In the study, psychiatrist and neurologist David Silbersweig, MD, radiologist
Emily Stern, MD, of Cornell University,
and colleagues at MRC cyclotron facility, Hammersmith
Hospital in London observed that hallucinating patients share
a similar pattern of activity in a set of interconnected regions deep in
the brain. Silbersweig and colleagues used positron emission tomography
(PET) to study six hallucinating schizophrenics. Participants were told
to press buttons connected to the scanner whenever they heard voices talking
to them or saw hallucinatory images. Five of the participants were
experiencing auditory hallucinations even though they were on medications,
and one had both auditory and visual hallucinations and was not taking
medication. The team was aided in the study by colleagues at Hammersmith
Hospital in London.
In the five patients experiencing auditory hallucinations, PET showed strong
activity in systems associated with the frontal lobe, a neocortical
area responsible for integrating current and past events, language, cognitive
concepts of space and time, and emotions (Module
5: Principles of Psychobiology). The areas included the mediodorsal
thalamic region, left hippocampus/parahippocampal gyri, right anterior
cingulate neocortex and left orbitofrontal cortex. Many of these regions
have been implicated by other research as being involved in schizophrenia.
In addition, the single patient experiencing both auditory and visual hallucinations
showed activity in the visual association cortex and the auditory association
cortex. Most of the neocortical activity in this patient took place in
the left hemisphere, where language-related information would be
integrated with visual information. When activity of neocortical structures
was compared to the subcortical structures, activity in the subcortical
brain regions was abnormally high.
When "normal" people hear real voices or see real images, their brains
show similar patterns of activation in the neocortex, but fewer of the
subcortical brain regions are activated, Silbersweig said. This work
gives clues about where to look for a difference in the "hallucination
circuitry" of different people. For instance; very high levels of
activity in subcortical areas of schizophrenics may indicate that the hallucinations
are being "made" in those regions of the brain in the absence of "real"
external auditory or visual stimuli. When the neocortex receives input
from these abnormally active subcortical structures, it may not "test"
the validity of the input: The neocortex may simply "create
its own reality and believe it" based solely on the type of neural
input it receives. These results were published in Nature.
Here's
a thought question: Do you think that understanding these
brain mechanisms may also tell us something about the nature of dreams
or Visa Versa?
| Copyright©1998,1999,
Red Reef Publications, All Rights Reserved.
Last Update: 08/25/1999 Return to Principles Home Page |