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From: ironjustice on 10 Aug 2008 20:57
Journal of Pharmacology And Experimental Therapeutics Fast Forward

NEUROPHARMACOLOGY

Reversal of Oxidative Stress-Induced Anxiety by Inhibition of
Phosphodiesterase-2 in Mice
Anbrin Masood, Ahmed Nadeem, S. Jamal Mustafa, and James M. O'Donnell
Departments of Behavioral Medicine and Psychiatry and Neurobiology and
Anatomy (A.M., J.M.O.) and Physiology and Pharmacology (A.N., S.J.M.),
West Virginia University Health Sciences Center, Morgantown, West
Virginia


The pathogenesis of several neuropsychiatric disorders, including
anxiety and depression, has been linked to oxidative stress, in part
via alterations in cyclic nucleotide signaling. Phosphodiesterase-2
(PDE2), which regulates cGMP and cAMP signaling, may affect anxiety-
related behavior through reduction of oxidative stress.
The present study evaluated the effects of oxidative stress on
behavior and assessed the anxiolytic effects of the PDE2 inhibitor Bay
60-7550 [(2-(3,4-dimethoxybenzyl)-7-{(1R)-1-[(1R)-1-hydroxyethyl]-4-
phenylbutyl}-5-methyl imidazo-[5,1-f][1,2,4]triazin-4(3H)-one)].
Treatment of mice with L-buthionine-(S,R)-sulfoximine (300 mg/kg), an
inducer of oxidative stress, caused anxiety-like behavioral effects in
elevated plusmaze, open-field, and hole-board tests through the NADPH
oxidase pathway; these effects were antagonized by Bay 60-7550 (3 mg/
kg) and apocynin (3 mg/kg), an inhibitor of NADPH oxidase.
The Bay 60-7550-mediated decrease in oxidative stress (i.e.,
superoxide anion and reactive oxygen species generation in cultured
neurons and total antioxidant capacity and lipid peroxides in amygdala
and hypothalamus) and expression of NADPH oxidase subunits (i.e., p47
phox and gp91 phox expression in amygdala, hypothalamus, and cultured
neurons) was associated with increased cGMP and phosphorylation of
vasodilator-stimulated phosphoprotein at Ser239, suggesting an
important role of cGMP-protein kinase G signaling in reduction of
anxiety. Overall, the present results indicate that oxidative stress
induces anxiety-like behavior in mice and that PDE2 inhibition
reverses it through an increase in cGMP signaling.
Thus, PDE2 may be a novel pharmacological target for treatment of
anxiety in neuropsychiatric and neurodegenerative disorders that
involve oxidative stress.

Received January 28, 2008; accepted May 1, 2008.
Address correspondence to: Dr. Anbrin Masood, West Virginia
University, P.O. Box 9128, Morgantown, WV 26506. E-mail:
amasood(a)hsc.wvu.edu
First published on May 2, 2008; DOI: 10.1124/jpet.108.137208
0022-3565/08/3262-369-379$20.00
JPET 326:369-379, 2008

---------------------------------

"Chelation of iron prevented the hyperactivity"

Behav Brain Res. 2004 Oct 5;154(2):321-9. Related Articles, Links


Stress-induced behaviour in juvenile rats: effects of neonatal
asphyxia, body temperature and chelation of iron.


Rogalska J, Caputa M, Wentowska K, Nowakowska A.


Department of Animal Physiology, Institute of General and Molecular
Biology, N.
Copernicus University, ul. Gagarina 9, 87-100 Torun, Poland.
ro...(a)biol.uni.torun.pl


Newborn mammals, showing reduced normal body temperature, might be
protected against iron-mediated, delayed neurotoxicity of perinatal
asphyxia.
Therefore, we investigated the effects of (1) neonatal body
temperature and neonatal critical anoxia as well as (2) postanoxic
chelation of iron with deferoxamine, on open-field stress-induced
behaviour in juvenile rats.
The third aim of this study was to compare (after the above-mentioned
treatments) circadian changes in spontaneous motor activity and body
temperature in juvenile rats permanently
protected from any stress.
Neonatal anoxia at body temperature adjusted (both during anoxia and 2
h reoxygenation) to a level typical of healthy (37 degrees
C) or febrile (39 degrees C) adults led to the stress-induced
hyperactivity in juvenile (5-45 days old) rats.
Both normal neonatal body temperature of 33 degrees C and chelation of
iron prevented the hyperactivity in rats.
Neither neonatal body temperature nor neonatal anoxia affected
spontaneous motor activity or body temperature of juvenile rats,
recorded in their home-cages with implantable transmitters. Circadian
rhythmicity was also undisturbed.
Presented data support the hypothesis that physiologically reduced
neonatal body temperature can provide a protection against iron-
mediated postanoxic disturbances of behavioural stress responses in
juvenile rats.


PMID: 15313019

---------------------------------------------

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Tom


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From: jay on 11 Aug 2008 00:44
> Thus, PDE2 may be a novel pharmacological target for treatment of
> anxiety in neuropsychiatric and neurodegenerative disorders that
> involve oxidative stress.

Induction of Oxidative Stress Responses by Dioxin and other Ligands of
the Aryl Hydrocarbon Receptor.
TCDD and other polyhalogenated aromatic hydrocarbon ligands of the
aryl hydrocarbon receptor (AHR) have been classically considered as
non-genotoxic compounds because they fail to be directly mutagenic in
either bacteria or most in vitro assay systems. They do so in spite of
having repeatedly been linked to oxidative stress and to mutagenic and
carcinogenic outcomes. Oxidative stress, on the other hand, has been
used as a marker for the toxicity of dioxin and its congeners. We have
focused this review on the connection between oxidative stress
induction and the toxic effects of fetal and adult dioxin exposure,
with emphasis on the large species difference in sensitivity to this
agent. We examine the roles that the dioxin-inducible cytochromes
P450s play in the cellular and toxicological consequences of dioxin
exposure with emphasis on oxidative stress involvement. Many
components of the health consequences resulting from dioxin exposure
may be attributable to epigenetic mechanisms arising from prolonged
reactive oxygen generation. PMID: 18648615

> ---------------------------------
> Presented data support the hypothesis that physiologically reduced
> neonatal body temperature can provide a protection against iron-
> mediated postanoxic disturbances of behavioural stress responses in
> juvenile rats.

Stimulation of iron absorption by polychlorinated aromatic
hydrocarbons.
Concomitant with iron transport stimulation, aryl hydrocarbon
hydroxylase activity in the intestine and liver is increased by TCDD
treatment. These studies suggest that polychlorinated aromatic
hydrocarbons, which are environmental health hazards, may effect the
intestinal absorption of essential mineral nutrients. PMID: 443429
From: ironjustice on 11 Aug 2008 01:02
On Aug 10, 9:44 pm, jay <jaym1...(a)hotmail.com> wrote: "Chelation of
iron prevented the hyperactivity" <<

"may effect the intestinal absorption of essential mineral nutrients"

I guess this is your roundabout way of saying ..

"Yes targeting iron should work" ..

Is .. it .. ?

You can't seem to answer a direct question ON .. **my** threads ..
there .. buddy ..

You got a problem with English .. ?


Who loves ya.
Tom


Jesus Was A Vegetarian!
http://tinyurl.com/2r2nkh


Man Is A Herbivore!
http://tinyurl.com/4rq595


DEAD PEOPLE WALKING
http://tinyurl.com/zk9fk



> > Thus, PDE2 may be a novel pharmacological target for treatment of
> > anxiety in neuropsychiatric and neurodegenerative disorders that
> > involve oxidative stress.
>
> Induction of Oxidative Stress Responses by Dioxin and other Ligands of
> the Aryl Hydrocarbon Receptor.
> TCDD and other polyhalogenated aromatic hydrocarbon ligands of the
> aryl hydrocarbon receptor (AHR) have been classically considered as
> non-genotoxic compounds because they fail to be directly mutagenic in
> either bacteria or most in vitro assay systems. They do so in spite of
> having repeatedly been linked to oxidative stress and to mutagenic and
> carcinogenic outcomes. Oxidative stress, on the other hand, has been
> used as a marker for the toxicity of dioxin and its congeners. We have
> focused this review on the connection between oxidative stress
> induction and the toxic effects of fetal and adult dioxin exposure,
> with emphasis on the large species difference in sensitivity to this
> agent. We examine the roles that the dioxin-inducible cytochromes
> P450s play in the cellular and toxicological consequences of dioxin
> exposure with emphasis on oxidative stress involvement. Many
> components of the health consequences resulting from dioxin exposure
> may be attributable to epigenetic mechanisms arising from prolonged
> reactive oxygen generation. PMID: 18648615
>
> > ---------------------------------
> > Presented data support the hypothesis that physiologically reduced
> > neonatal body temperature can provide a protection against iron-
> > mediated postanoxic disturbances of behavioural stress responses in
> > juvenile rats.
>
> Stimulation of iron absorption by polychlorinated aromatic
> hydrocarbons.
> Concomitant with iron transport stimulation, aryl hydrocarbon
> hydroxylase activity in the intestine and liver is increased by TCDD
> treatment. These studies suggest that polychlorinated aromatic
> hydrocarbons, which are environmental health hazards, may effect the
> intestinal absorption of essential mineral nutrients. PMID: 443429

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