Why a Cat in the House May Cause Depression and Suicide
Suicide accounts for approximately one death every 14 minutes. In
2009, there were 36,909 reported suicide deaths in the U.S. A primary
risk factor of suicide includes repeated non-fatal attempts to commit
suicide. Other risk factors or potential signs of impeding suicide
such as changes in behavior, increased use of alcohol, or a recent
death in the family offer little warning that someone may be depressed
and considering to commit suicide. While an estimated 90% of all
suicides are attributed to a diagnosed psychiatric disorder,
researchers recently report that some cases of suicide may be linked
to a common parasite found in cats.
In the August issue of the Journal of Clinical Psychology, researchers
explain that some cases of suicide could be due to Toxoplasma gondii
infection—an intracellular parasite hosted by cats that is passed onto
humans. According to the researchers, Toxoplasma gondii may be carried
by as much as 10% to 20% of the population.
Toxoplasma gondii is a single-celled parasitic organism that
reproduces only in cats—both wild and domestic—and therefore is a
carrier host for human infection.
According to the CDC, toxoplasmosis is considered to be a leading
cause of death attributed to foodborne illness in the United States.
While a large portion of the population carries the parasite, the
majority are symptomless due to the protective abilities of a healthy
immune system. In immunocompromised or people with a weakened immune
system due to some medications or illness, the parasite can forms
cysts that can adversely affect your muscles, your heart—and even your
brain.
Infection in humans is typically due to:
• Coming into contact with cat feces that contain the parasite
• Eating contaminated food or drinking contaminated water
• Eating unwashed fruits and vegetables
• Using contaminated knives, cutting boards or other utensils
• Receiving an infected organ during transplantation surgery or
transfused blood
While depression is often attributed to low or significantly decreased
levels of an important brain chemical called “serotonin,” previous
research has led investigators to consider that the low levels of
serotonin may be a symptom rather than a cause of depression. One
hypothesis is that parasitic organisms that can get to the brain may
cause inflammation that over time produces harmful metabolites that
damage brain cells.
“Previous research has found signs of inflammation in the brains of
suicide victims and people battling depression, and there also are
previous reports linking Toxoplasma gondii to suicide attempts,” says
Lena Brundin a researcher at Michigan State University and co-author
of the study. “In our study we found that if you are positive for the
parasite, you are seven times more likely to attempt suicide.”
In the study, 54 participants who had previously attempted suicide and
30 non-suicidal participants were given a version of a Suicide
Assessment Scale questionnaire as well as the Montgomery Asberg
Depression Rating Scale exam. The tests reportedly assess the level of
a person’s depression and are predictive of the risk a person is for
committing suicide.
What the researchers found was a positive association between testing
positive for Toxoplasma gondii infection and scoring high on the
suicide assessment tests.
The researchers believe that their results indicate that detection of
Toxoplasma gondii infection may be a candidate marker/ risk factor
toward identifying potential suicides before they happen and thereby
provide opportunity for timely and successful intervention.
For more information about the study and its results, Michigan State
University offers a free online copy of the study.
Reference: “Toxoplasma gondii Immunoglobulin G Antibodies and Nonfatal
Suicidal Self-Directed Violence” Journal of Clinical Psychiatry 73(8),
pp. 1069-1076, (Aug. 2012); Yuanfen Zhang, MD, PhD et al.
50% world population infected and controlled by this dopamine
producing parasite ...
----------------------------
Dopamine: Is this how Toxoplasma gondii controls your brain?
It’s estimated that 15 percent of people in the UK are infected with
Toxoplasma Gondii (Toxo), a bizarre mind-altering parasite capable of
driving rodents to suicide. Now scientists have discovered this
peculiar creature directly affects the production of dopamine in the
mammalian brain.
For a long time people speculated that there could be a link between
Toxo and dopamine, but now researchers from the University of Leeds
have proven that in an affected brain, Toxo produces and releases many
times the normal level of the hormone.
The research goes hand in hand with a previous study carried out by
lead scientist Dr Glenn McConkey that found Toxo had the enzyme for
producing dopamine encoded into its genome.
It could be this abundance of dopamine that encourages rodents to
approach, rather than run from, their predators (cats) as the hormone
regulates fear and, in some cases, encourages the animal to seek
sensations, some even believe the rodent becomes sexually attracted to
the cat.
Toxo prefers to make its home in the brains of rodents, as it can only
breed in the intestines of cats who ingest the parasite after eating
there willing rodent meal. But, due to our close relationship with
felines, we can often become the mind-bending bugs accidental hosts.
Dr McConkey believes this new research could shed more light on the
treatment of human neurological conditions accosotaed with dopamine
such as schizophrenia, Parkinsons disease and attention deficit
hyperactivity disorder (ADHD).
T. gondii brain parasite found to alter dopamine production
The brain parasite Toxoplasma gondii, found in an estimated 15 percent
of the population, has been found to dramatically increase the
production of dopamine, one of the brain's key chemical messengers. T.
gondii has previously been linked to a whole raft of brain disorders
and some scientists speculate that the parasite affects human behavior
on a mass scale. The new findings are the first to demonstrate that a
parasite found in the brain of mammals can affect dopamine levels.
The dopamine discovery, made by a research group at the University of
Leeds working with rodents, builds on the group's earlier work which
showed that the parasite encodes the enzyme for producing dopamine in
its genome.
Lead investigator Glenn McConkey believes that the findings could
ultimately shed light on treating human neurological disorders that
are dopamine-related such as schizophrenia, attention deficit
hyperactivity disorder and Parkinson's disease.
McConkey's research may explain how these parasites manipulate
rodents' behavior for their own advantage. Infected rodents lose their
innate fear of cats, increasing the chances of being caught and eaten,
which enables the parasite to return to its main host to complete its
life cycle.
Dopamine is a natural chemical which helps control the brain's reward
and pleasure centers and regulates emotional responses such as fear.
The presence of a certain kind of dopamine receptor is also associated
with sensation-seeking, whereas dopamine deficiency in humans results
in Parkinson's disease. "Based on these analyses, it was clear that T.
gondii can orchestrate a significant increase in dopamine production
in neural cells," noted McConkey.
McConkey is reticent to translate the parasite's dopamine manipulation
in rodents directly to humans, but concedes there may be a link
between T. gondii and certain psychiatric illnesses. "Humans are
accidental hosts to T. gondii and the parasite could end up anywhere
in the brain, so human symptoms of toxoplasmosis infection may depend
on where parasite ends up. This may explain the observed statistical
link between incidences of schizophrenia and toxoplasmosis infection."
McConkey now plans to investigate how the parasite enzyme triggers
dopamine production and precisely how this may change behavior.
> Why a Cat in the House May Cause Depression and Suicide
> Suicide accounts for approximately one death every 14 minutes. In
> 2009, there were 36,909 reported suicide deaths in the U.S. A primary
> risk factor of suicide includes repeated non-fatal attempts to commit
> suicide. Other risk factors or potential signs of impeding suicide
> such as changes in behavior, increased use of alcohol, or a recent
> death in the family offer little warning that someone may be depressed
> and considering to commit suicide. While an estimated 90% of all
> suicides are attributed to a diagnosed psychiatric disorder,
> researchers recently report that some cases of suicide may be linked
> to a common parasite found in cats.
> In the August issue of the Journal of Clinical Psychology, researchers
> explain that some cases of suicide could be due to Toxoplasma gondii
> infection—an intracellular parasite hosted by cats that is passed onto
> humans. According to the researchers, Toxoplasma gondii may be carried
> by as much as 10% to 20% of the population.
> Toxoplasma gondii is a single-celled parasitic organism that
> reproduces only in cats—both wild and domestic—and therefore is a
> carrier host for human infection.
> According to the CDC, toxoplasmosis is considered to be a leading
> cause of death attributed to foodborne illness in the United States.
> While a large portion of the population carries the parasite, the
> majority are symptomless due to the protective abilities of a healthy
> immune system. In immunocompromised or people with a weakened immune
> system due to some medications or illness, the parasite can forms
> cysts that can adversely affect your muscles, your heart—and even your
> brain.
> Infection in humans is typically due to:
> • Coming into contact with cat feces that contain the parasite
> • Eating contaminated food or drinking contaminated water
> • Eating unwashed fruits and vegetables
> • Using contaminated knives, cutting boards or other utensils
> • Receiving an infected organ during transplantation surgery or
> transfused blood
> While depression is often attributed to low or significantly decreased
> levels of an important brain chemical called “serotonin,” previous
> research has led investigators to consider that the low levels of
> serotonin may be a symptom rather than a cause of depression. One
> hypothesis is that parasitic organisms that can get to the brain may
> cause inflammation that over time produces harmful metabolites that
> damage brain cells.
> “Previous research has found signs of inflammation in the brains of
> suicide victims and people battling depression, and there also are
> previous reports linking Toxoplasma gondii to suicide attempts,” says
> Lena Brundin a researcher at Michigan State University and co-author
> of the study. “In our study we found that if you are positive for the
> parasite, you are seven times more likely to attempt suicide.”
> In the study, 54 participants who had previously attempted suicide and
> 30 non-suicidal participants were given a version of a Suicide
> Assessment Scale questionnaire as well as the Montgomery Asberg
> Depression Rating Scale exam. The tests reportedly assess the level of
> a person’s depression and are predictive of the risk a person is for
> committing suicide.
> What the researchers found was a positive association between testing
> positive for Toxoplasma gondii infection and scoring high on the
> suicide assessment tests.
> The researchers believe that their results indicate that detection of
> Toxoplasma gondii infection may be a candidate marker/ risk factor
> toward identifying potential suicides before they happen and thereby
> provide opportunity for timely and successful intervention.
> For more information about the study and its results, Michigan State
> University offers a free online copy of the study.
> Reference: “Toxoplasma gondii Immunoglobulin G Antibodies and Nonfatal
> Suicidal Self-Directed Violence” Journal of Clinical Psychiatry 73(8),
> pp. 1069-1076, (Aug. 2012); Yuanfen Zhang, MD, PhD et al.
On Aug 21, 4:07 am, Happy Oyster <-*-*.@.*-*-> wrote:
> On Mon, 20 Aug 2012 08:52:58 -0700 (PDT), Taka <taka0...@gmail.com>
> wrote:
> >Why a Cat in the House May Cause Depression and Suicide
> Wonderful article about Jaroslav Flegr:
> "How Your Cat Is Making You Crazy"http://t.co/TXqt3TIC
Very interesting indeed!
He is a typical victim of the parasite high on testosterone - balding,
robust jaws, red hair ...
QUOTE: He’s published some data, he tells me, that suggest infected
males might have elevated testosterone levels. Possibly for that
reason, women shown photos of these men rate them as more masculine
than pictures of uninfected men. “I want to investigate this more
closely to see if it’s true,” he says. “Also, it could be women find
infected men more attractive. That’s something else we hope to test.”
UNQUOTE.
If you want a testosterone supplement for life free of charge just
lick your cat's feces! And you get the bonus of lifelong protection
from the pituitary tumor prolactinoma too! But perhaps you will spend
more money for women/sex and at the end for the prostate cancer
treatment not speaking of my hypothesis that T shortens the maximal
lifespan ...
On Aug 20, 11:02 pm, Taka <taka0...@gmail.com> wrote:
> If you want a testosterone supplement for life free of charge just
> lick your cat's feces! And you get the bonus of lifelong protection
> from the pituitary tumor prolactinoma too! But perhaps you will spend
> more money for women/sex and at the end for the prostate cancer
> treatment not speaking of my hypothesis that T shortens the maximal
> lifespan ...
On Aug 21, 12:02 pm, Taka <taka0...@gmail.com> wrote:
> QUOTE: He’s published some data, he tells me, that suggest infected
> males might have elevated testosterone levels. Possibly for that
> reason, women shown photos of these men rate them as more masculine
> than pictures of uninfected men. “I want to investigate this more
> closely to see if it’s true,” he says. “Also, it could be women find
> infected men more attractive. That’s something else we hope to test.”
> UNQUOTE.
"Since T. gondii can reproduce sexually only in the cat, it has
learned how to get there. It enlists the help of rodents, which become
infected by eating cat droppings. As previously reported by Ajai Vyas,
Sapolsky, and others at Stanford University, the parasite turns rats’
innate, self-preserving dislike of the smell of cat urine into a fatal
feline attraction (Vyas et al., 2007). When T. gondii-infected male
rats smell "eau de cat," their testosterone levels rise and their
testes swell, which Sapolsky said shows that the odor “is smelling
sexually attractive to these males.” Drawn to the cat, the rat becomes
cat food, and T. gondii adds another generation to its family tree."
" It should not be forgotten, however, that dopamine is not the only
suspected molecule. There are several indirect and recently even
direct indications for changed levels of testosterone in subjects with
latent toxoplasmosis (Flegr et al., 2008). Moreover, the increased
levels of dopamine in Toxoplasma infected mice and men seem to be
byproducts of local brain inflammations, rather than a product of
biologically important manipulation of the host behavior by the
parasite. The results from human cytomegalovirus, i.e., the parasite
transmitted by direct contact, not by predation, suggest that an
infection of brain tissue by various parasites could increase the
level of brain dopamine"
Oh boy, it's easy to understand. E.g. you get the bright sunlight
into your eyes in the morning and it shuts down melatonin and other
night hormones (as prolactin) and triggers dopamine release which in
turn stimulates the release of testosterone. It's a known fact that
dopamine raises the testosterone.
On Aug 21, 1:03 am, Taka <taka0...@gmail.com> wrote:
> 50% world population infected and controlled by this dopamine
> producing parasite ...
> Human infection by T. gondii is common. Worldwide, rates vary between
> 20 - 80 percent of the population
Men with cat-litter disease are manlier
About half of all men have cysts in their brains, heart and muscles
that contain the single-celled parasite Toxoplasma gondii. The most
likely origin of the parasite? Cats' droppings. According to
parasitologists at Charles University in Prague, men who are infected
with the parasite have higher testosterone levels.
You might not be aware of it, but you've probably got cysts containing
parasites in your muscles and brain. If you haven't, don't worry;
you'll probably develop them sooner or later. Up to half of humanity
is infected with the Toxoplasma gondii organism. [Ned Tijdschr Klin
Chem 1999; 24: 65-70.] Every year of your time spent on this planet,
the chance of your body being invaded by this parasite grows.
According to a Dutch study, 20 percent of all people in their twenties
are infected, and 90 percent of people in their seventies.
Well this can come as far that some "science hero" will claim that
prostate cancer is caused by this parasite like they blame stomach
cancer on Helicobacter or AIDS on HIV.
On Aug 21, 11:16 pm, Taka <taka0...@gmail.com> wrote:
> Well this can come as far that some "science hero" will claim that
> prostate cancer is caused by this parasite like they blame stomach
> cancer on Helicobacter or AIDS on HIV.
On the contrary, prostate cancer just like the majority of cancers in
older adults is caused by vitamin D insufficiency.
The only loop hole that I see so far with the vitamin D insufficiency
theory of cancer development are children who develop cancer. Of
course, I know of no doctor who has seriously treated childhood cancer
patients with massive amounts of vitamin D. So it is more of an
unknown than a negative finding.
Toxoplasma gondii secretes a calcium-independent phospholipase A(2).
Cassaing S, Fauvel J, Bessières MH, Guy S, Séguéla JP, Chap H.
Département de Parasitologie et Mycologie, UPRES-EA 2405, Centre
Hospitalier Universitaire, Hôpital Rangueil, 1 avenue du Professeur
Jean Poulhès, 31054 Toulouse, Cedex 4, France.
Phospholipases A(2) (PLA(2)) play an important role in Toxoplasma
gondii host cell penetration. They are also key enzymes in the host
cell response to the parasite invasion. PLA(2) hydrolyse cellular
phospholipids, releasing multiple inflammatory lipidic mediators. We
have investigated the biochemical characterisation of T. gondii PLA(2)
activity in a mouse-cultured tachyzoite homogenate and in the
peritoneal exudate from infected mice, using the hydrolysis of a
fluorescent phosphatidylglycerol labelled at the sn-2 position.
Spectrofluorimetry and thin-layer chromatography showed a PLA(2)
activity (about 0.5-2 nmol/min per mg), calcium-independent, secreted
into infected mice peritoneal exudate, with a broad pH activity
ranging between 6.5 and 9.5 and resistant to a great number of
potential PLA(2) inhibitors except dithio-nitrobenzoic acid (1 mM). An
associated phospholipase A(1) activity was also displayed. These
results suggest that Toxoplasma gondii displays specific
phospholipases different from host enzymes and probably involved at
critical steps of infectious cycle.
PMID: 11027777
-------------------
Another parasite exploiting the arachidonic acid charged humans ...
Taka
The microscopic parasite Toxoplasma gondii is small enough to get
inside the cells of the animals it infects. A single-celled organism
known as a protozoan, it has a complicated life cycle involving
rodents and cats. Toxoplasma can also infect humans and farm animals,
but these species are accidental hosts.
The parasite can only reproduce sexually and form eggs within cats,
which can shed millions of toxoplasma “oocysts” in their faeces. Cats
become infected if they eat contaminated raw meat, or catch and eat
infected mice or rats.
Cats can shed up to 10 million oocysts a day for up to 14 days after
they initially become infected. Given that there are 8 million pet
cats in Britain and 1 per cent of them are shedding toxoplasma oocysts
at any one time, this means there are in the region of 800 billion
toxoplasma eggs being released each day in Britain by domestic cats.
Toxoplasma oocysts in the soil remain viable for several years where
they can be ingested by other animals which then become infected with
tissue cysts in their vital organs, including brain and muscle tissue.
A survey of 51 cats on 22 sheep farms the South West of England found
that nearly half the felines carried antibodies to toxoplasma,
indicating past exposure to the parasite.
Lamb meat has been shown from limited testing to carry the greatest
risk of toxoplasma based on past exposure to the parasite by various
farm animals.
Fuller Torrey, director of the Stanley Medical Research Institute in
Maryland, carried out studies of playground sandpits that are left
uncovered at night and found that they are a favourite haunt of cats,
which prefer to defecate in loose sand and soil.
“I’ve just been looking at the data on levels of oocysts secreted by
cats and I’m frankly appalled at the level of contamination of areas
where they go to the bathroom,” Dr Torrey said.
“I estimated in some of these public sandboxes [sandpits] there are
about a million viable oocysts per square foot of sand. I would not
let any children of mine play in a sandbox that had not been covered
at all times when not in use, or in a sheltered place that cats could
not enter,” he said.
Dr Torrey said that he would go as far as to recommend against having
cats as pets if there are young children in a household.
“I would certainly advise families not to get a cat if they have small
children. I gave this advice to my own daughter and granddaughter,” he
said.
Toxoplama infection can result from the ingestion of oocysts or from
tissues cysts that form in the muscle of infected farm animals. Most
people show no symptoms but it is estimated that between 10 and 20 per
cent of infected individuals develop flu-like symptoms in the early,
acute stages of the infection.
The latent stage of toxoplasma is normally without obvious clinical
symptoms but it can develop into serious illness when people become
immune-compromised, for instance during Aids or when undergoing
certain types of cancer treatment. One notable manifestation in immune-
compromised patients is toxoplasmic encephalitis of the brain, which
can be lethal.
If women become infected with toxoplasma while pregnant, the parasite
can seriously damage the development of their baby in the womb,
leading to miscarriage or congenital birth problems.
Toxoplasma is the second most common cause of abortion in sheep,
resulting in the loss of more than 500,000 lambs a year at a cost of
up to £24m. Sheep acquire the infection by eating oocysts on pasture
grass or from concentrated feed contaminated with cat faeces.
A survey of 3,539 blood samples taken from breeding ewes in Britain
revealed that 68.6 per cent are positive for toxoplasma antibodies,
indicating past exposure to the parasite.
On Aug 21, 11:16 pm, Taka <taka0...@gmail.com> wrote:
> Well this can come as far that some "science hero" will claim that
> prostate cancer is caused by this parasite like they blame stomach
> cancer on Helicobacter or AIDS on HIV.
On the contrary, prostate cancer just like the majority of cancers in
older adults is caused by vitamin D insufficiency.
The only loop hole that I see so far with the vitamin D insufficiency
theory of cancer development are children who develop cancer. Of
course, I know of no doctor who has seriously treated childhood cancer
patients with massive amounts of vitamin D. So it is more of an
unknown than a negative finding.
> On Fri, 14 Sep 2012 04:59:13 -0700 (PDT), in sci.med.nutrition, "John
> H. Gohde" <john.h.go...@gmail.com> wrote:
> >On Aug 21, 11:16 pm, Taka <taka0...@gmail.com> wrote:
> >> Well this can come as far that some "science hero" will claim that
> >> prostate cancer is caused by this parasite like they blame stomach
> >> cancer on Helicobacter or AIDS on HIV.
> >On the contrary, prostate cancer just like the majority of cancers in
> >older adults is caused by vitamin D insufficiency.
> Why are you so worried, John. I do not take mega doses of anything,
> and don't have any worries about prostate cancer.
> You take massive doses and seem to do nothing but worry about your
> own little problem.
> >The only loop hole that I see so far with the vitamin D insufficiency
> >theory of cancer development are children who develop cancer. Of
> >course, I know of no doctor who has seriously treated childhood cancer
> >patients with massive amounts of vitamin D. So it is more of an
> >unknown than a negative finding.
> That isn't a loop hole, that is a giant crater.
> Try learning something about what you are mumbling about, stop
> playing doctor, get help for you mental disorder, and stop the lies
> you tell.
> And even intelligent/smart people get cancer.
> --
> Ak'toh'di
In case, the Comatose Science Psycho don't know, I am a spry senior
citizen. Vitamin D works for my age group, and that is all that I
care about.
The fact that Science Psychos are NOT treating childhood cancer
patients with vitamin D is precisely why THEY should be criminally
prosecuted. :)
> On Fri, 14 Sep 2012 08:30:40 -0700 (PDT), in sci.life-extension,
> "John H. Gohde" <john.h.go...@gmail.com> wrote:
> >On Sep 14, 10:50 am, Bob Officer <boboffic...@127.0.0.7> wrote:
> >> On Fri, 14 Sep 2012 04:59:13 -0700 (PDT), in sci.med.nutrition, "John
> >> H. Gohde" <john.h.go...@gmail.com> wrote:
> >> >On Aug 21, 11:16 pm, Taka <taka0...@gmail.com> wrote:
> >> >> Well this can come as far that some "science hero" will claim that
> >> >> prostate cancer is caused by this parasite like they blame stomach
> >> >> cancer on Helicobacter or AIDS on HIV.
> >> >On the contrary, prostate cancer just like the majority of cancers in
> >> >older adults is caused by vitamin D insufficiency.
> >> Why are you so worried, John. I do not take mega doses of anything,
> >> and don't have any worries about prostate cancer.
> >> You take massive doses and seem to do nothing but worry about your
> >> own little problem.
> >> >The only loop hole that I see so far with the vitamin D insufficiency
> >> >theory of cancer development are children who develop cancer. Of
> >> >course, I know of no doctor who has seriously treated childhood cancer
> >> >patients with massive amounts of vitamin D. So it is more of an
> >> >unknown than a negative finding.
> >> That isn't a loop hole, that is a giant crater.
> >> Try learning something about what you are mumbling about, stop
> >> playing doctor, get help for you mental disorder, and stop the lies
> >> you tell.
> >> And even intelligent/smart people get cancer.
> >In case, the Comatose Science Psycho don't know, I am a spry senior
> >citizen. Vitamin D works for my age group, and that is all that I
> >care about.
> You not more than a year or two older than I am, John. I have Zero
> sign of prostate cancer. and I am considered a very active and a spry
> person.
> Matter of Fact as I consider retirement from one job after 43 years,
> I have several offers of part time consultation waiting in the wings,
> If I wish.
> >The fact that Science Psychos are NOT treating childhood cancer
> >patients with vitamin D is precisely why THEY should be criminally
> >prosecuted. :)
> You have no idea of what you are talking about John.
> BTW next time you write about taking "aim" and "pulling triggers", be
> careful. Because with your apparent mental disability, the police
> might show up at your house.
Sorry, but you have ALREADY proved operationally my theory that the
frustrated Police Offiiccers are just a bunch of comatose fools. :)
PLoS One. 2012;7(8):e41499. Epub 2012 Aug 22.
Cytosolic Phospholipase A(2) alpha/Arachidonic Acid Signaling Mediates
Depolarization-Induced Suppression of Excitation in the Cerebellum.
Wang DJ, Yang D, Su LD, Xie YJ, Zhou L, Sun CL, Wang Y, Wang XX, Zhou
L, Shen Y.
Source
Key Laboratory of Medical Neurobiology of the Ministry of Health,
Zhejiang Province Key Laboratory of Neurobiology, Department of
Neurobiology, Zhejiang University School of Medicine, Hangzhou,
People's Republic of China.
Abstract
BACKGROUND:
Depolarization-induced suppression of excitation (DSE) at parallel
fiber-Purkinje cell synapse is an endocannabinoid-mediated short-term
retrograde plasticity. Intracellular Ca(2+) elevation is critical for
the endocannabinoid production and DSE. Nevertheless, how elevated
Ca(2+) leads to DSE is unclear.
METHODOLOGY/PRINCIPAL FINDINGS:
We utilized cytosolic phospholipase A(2) alpha (cPLA(2)α) knock-out
mice and whole-cell patch clamp in cerebellar slices to observed the
action of cPLA(2)α/arachidonic acid signaling on DSE at parallel fiber-
Purkinje cell synapse. Our data showed that DSE was significantly
inhibited in cPLA(2)α knock-out mice, which was rescued by arachidonic
acid. The degradation enzyme of 2-arachidonoylglycerol (2-AG),
monoacylglycerol lipase (MAGL), blocked DSE, while another catabolism
enzyme for N-arachidonoylethanolamine (AEA), fatty acid amide
hydrolase (FAAH), did not affect DSE. These results suggested that 2-
AG is responsible for DSE in Purkinje cells. Co-application of
paxilline reversed the blockade of DSE by internal K(+), indicating
that large conductance Ca(2+)-activated potassium channel (BK) is
sufficient to inhibit cPLA(2)α/arachidonic acid-mediated DSE. In
addition, we showed that the release of 2-AG was independent of
soluble NSF attachment protein receptor (SNARE), protein kinase C and
protein kinase A.
CONCLUSIONS/SIGNIFICANCE:
Our data first showed that cPLA(2)α/arachidonic acid/2-AG signaling
pathway mediates DSE at parallel fiber-Purkinje cell synapse.
> PLoS One. 2012;7(8):e41499. Epub 2012 Aug 22.
> Cytosolic Phospholipase A(2) alpha/Arachidonic Acid Signaling Mediates
> Depolarization-Induced Suppression of Excitation in the Cerebellum.
> Wang DJ, Yang D, Su LD, Xie YJ, Zhou L, Sun CL, Wang Y, Wang XX, Zhou
> L, Shen Y.
> Source
> Key Laboratory of Medical Neurobiology of the Ministry of Health,
> Zhejiang Province Key Laboratory of Neurobiology, Department of
> Neurobiology, Zhejiang University School of Medicine, Hangzhou,
> People's Republic of China.
> Abstract
> BACKGROUND:
> Depolarization-induced suppression of excitation (DSE) at parallel
> fiber-Purkinje cell synapse is an endocannabinoid-mediated short-term
> retrograde plasticity. Intracellular Ca(2+) elevation is critical for
> the endocannabinoid production and DSE. Nevertheless, how elevated
> Ca(2+) leads to DSE is unclear.
> METHODOLOGY/PRINCIPAL FINDINGS:
> We utilized cytosolic phospholipase A(2) alpha (cPLA(2)α) knock-out
> mice and whole-cell patch clamp in cerebellar slices to observed the
> action of cPLA(2)α/arachidonic acid signaling on DSE at parallel fiber-
> Purkinje cell synapse. Our data showed that DSE was significantly
> inhibited in cPLA(2)α knock-out mice, which was rescued by arachidonic
> acid. The degradation enzyme of 2-arachidonoylglycerol (2-AG),
> monoacylglycerol lipase (MAGL), blocked DSE, while another catabolism
> enzyme for N-arachidonoylethanolamine (AEA), fatty acid amide
> hydrolase (FAAH), did not affect DSE. These results suggested that 2-
> AG is responsible for DSE in Purkinje cells. Co-application of
> paxilline reversed the blockade of DSE by internal K(+), indicating
> that large conductance Ca(2+)-activated potassium channel (BK) is
> sufficient to inhibit cPLA(2)α/arachidonic acid-mediated DSE. In
> addition, we showed that the release of 2-AG was independent of
> soluble NSF attachment protein receptor (SNARE), protein kinase C and
> protein kinase A.
> CONCLUSIONS/SIGNIFICANCE:
> Our data first showed that cPLA(2)α/arachidonic acid/2-AG signaling
> pathway mediates DSE at parallel fiber-Purkinje cell synapse.
