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The patient had failed to recover command-
specifically damaging oligodendrocytes, for
response or communication functions, despite
4 weeks and were subsequently tested on a
a 2-year course of inpatient rehabilitation and
Y-maze task. Treatment of mice with quetiapine
4 years in a nursing home. Functional MRI
beginning 1 week before introduction of cupri-
revealed a preserved large-scale bihemispheric
zone significantly prevented behavioral changes
cerebral language network. Inpatient rehabilita-
compared with the control group (P
tion was reinitiated, and the patient underwent
These findings suggest a mechanism for the
implantation of DBS electrodes 4 months later.
antipsychotic action of quetiapine that targets
An 18-week titration phase began 50 days after
oligodendrocytes. Furthermore, the data help
surgery, with the duration of alternating time on
to establish a role for oligodendrocytes in the
and off stimulation increasing from 3 days to
etiopathology of schizophrenia, although it is
14 days. Behavioral improvements, including
not clear whether oligodendrocytes can also be
longer periods of eye opening, increased com-
implicated in other neuropsychiatric disorders
mand response, improved functional object use
involving myelination development problems.
and intelligent verbalization, were noted shortly
The authors suggest that promyelinating treat-
after the initiation of the titration phase. Finally,
ment could be a viable therapeutic approach
the patient entered a crossover phase during
which DBS was alternately on and off for 30-day
Xiao L et al.
(2007) Quetiapine facilitates
periods. Improvements in cognitively mediated
oligodendrocyte development and prevents mice from
behaviors, functional limb control and oral feeding
myelin breakdown and behavioral changes. Mol Psychiatry
were associated with DBS-on periods.
The authors suggest that DBS might promote
functional recovery many years after an initial injury in MCS patients with only inter mittent
immunotherapy for AD
Schiff ND et al
. (2007) Behavioural
improvements with thalamic stimulation after severe
Experimental and clinical studies have suggested
traumatic brain injury. Nature 448:
that clearance of amyloid-β (Aβ) plaques can slow cognitive decline in Alzheimer’s disease (AD). Immunotherapy targeting Aβ has shown
promise in reducing plaques, but has adverse
oligodendrocytes and could be
effects including microhemorrhage and brain
a treatment for schizophrenia
inflammation. Wang et al.
recently tested the ability of a single-chain antibody against Aβ
Recent structural and neuroimaging studies
(scFv) to promote plaque clearance in a mouse
have reported white matter abnormalities in the
model of AD. This scFv lacks the normal anti-
brains of patients with schizophrenia, suggesting
body’s constant (Fc) region, which has been
that oligodendrocytes might be involved in the
suggested to mediate the detrimental side
etiopathology of this condition. To investigate
effects of other anti-Aβ immunotherapies.
this hypothesis, Xiao et al.
studied the response
The investigators first demonstrated that
of oligodendrocytes to antipsychotic drugs.
recombinant scFv could inhibit the formation
Neural progenitor cells (NPCs) isolated from
of Aβ fibrils and promote the disaggregation
rat fetuses were treated with a range of anti-
of preformed fibrils in vitro
. To test the tech-
psychotic drugs, but only quetiapine (in con-
nique in vivo
, the scFv gene was delivered by
junction with other growth factors) increased
recombined adeno-associated virus vectors
proliferation of NPCs in neurosphere cultures.
into 9-month-old transgenic mice with numer-
Quetiapine also stimulated NPCs to differentiate
ous brain Aβ deposits. Compared with control
into oligo dendrocytes, through extracellular signal-
animals, levels of Aβ peptide in the brains of
related kinases, and increased myelin basic pro-
treated animals were significantly lower follow-
tein expression in cortical aggregate cultures in
ing intramuscular (P
<0.05) as well as intra-
a dose-dependent manner (P
<0.0001). To test
<0.01) delivery of scFv. Three months
the effect of quetiapine on cortical myelin break-
after delivery, no antibodies against scFv
down in vivo
, 8-week-old mice were fed 0.2%
were detected, no T-lymphocyte infiltration
cuprizone, which causes myelin breakdown by
was observed, and there was no increase in
2007 Nature Publishing Group
the number of microhemorrhage profiles in
aid the development of therapies to alleviate
scFv-treated mice compared with controls.
comorbidities associated with shift work.
The results suggest that intramuscular delivery
Sookoian S et al
. (2007) Serotonin and
of scFv is as effective and safe as intra cranial
serotonin transporter gene variant in rotating shift workers.
delivery for reducing the total Aβ burden in a
mouse model of AD, and that neither mode of delivery elicits an inflammatory response.
Neurotrophin receptor p75
Wang Y-J et al.
delivery of a single chain antibody gene reduces brain Aβ
regulates the invasiveness
burden in a mouse model of Alzheimer’s disease. Neurobiol
of malignant gliomas
The highly invasive nature of malignant gliomas makes them very difficult to treat. To elucidate
Polymorphism in 5-HT transporter
the underlying mechanism of glioma invasive-
gene is associated with tolerance
ness, Johnston et al.
used serial in vivo
of rotating shift work
tion to establish a mouse model of the disease. These authors subsequently identified the p75
Desynchronization of circadian rhythms from
neurotrophin receptor (p75NTR) to be a major
environ mental conditions can have important
regulator of glioma invasion and migration. They
health implications for rotating shift workers (those
suggest that this receptor could be targeted to
who work shifts that rotate or change according
prevent recurrence of malignant gliomas.
to a set schedule). Those individuals have a high
The authors isolated a population of invasive
risk of developing cardio vascular and metabolic
cells from a noninvasive human glioma cell line
problems. Using a cohort of 683 Argentinian men
following implantation in immuno compromised
of European ancestry (437 day workers, 246 rotat-
mice. After reinjection into a new group of
ing shift workers), Sookoian et al.
the relationships between 5-hydroxytryptamine
cells migrated far from the original tumor
(5-HT; a neurotransmitter with an important role
site and formed tumors with highly infiltrative
in modulating circadian rhythms), 5-hydroxy-
edges; by contrast, reinjected noninvasive
indoleacetic acid (5-HIAA; a 5-HT metabolite),
cells resulted in large tumors with well-defined
functional polymorphism of the 5-HT transporter
borders. Microarray analyses revealed that
), and work schedule.
p75NTR was upregulated in the invasive cells
Platelet 5-HT and 5-HIAA content were both
and not expressed in tumor cells, and reverse-
greater in day workers than in shift workers.
transcriptase polymerase chain reaction and
Significantly decreased platelet 5-HIAA content,
western blot analysis confirmed that ectopic
but not platelet 5-HT content, was observed
expression of p75NTR induced migration and
in individuals homozygous for the SLC6A4
invasion in vitro
. Furthermore, upregulation of
promoter short variant, relative to other geno-
p75NTR in glioblastoma cells from various cell
types. The short (deletion) variant of the SLC6A4
lines dramatically increased their invasiveness
promoter reduces SLC6A4
. Disruption of the ability of p75NTR to
relative to the long (44 bp insertion) variant.
bind neurotrophin resulted in tumors similar
allele distribution differed
to those derived from noninvasive cells, indi-
between day workers and shift workers, with the
short allele being more prevalent in shift workers.
This difference was observed in individuals with
observed that p75NTR results in striking actin
at least 5 years’ exposure to their present work
cytoskeletal rearrangements in invading cells.
schedule, but not in those with shorter expo-
sure, indicating that individuals harboring short
strated that p75NTR is commonly expressed
variants (i.e. those with decreased
in glioblastoma multiforme, and that p75NTR-
serotonergic function) might better tolerate
positive cells migrate at a greater rate than do
shift work than those with long variants.
Johnston ALM et al.
(2007) The p75
neurotrophin receptor is a central regulator of glioma
circadian rhythm desynchronization might
invasion. PLoS Biol 5:
2007 Nature Publishing Group
J Oral Pathol Med (2004) 33: 445–50ª Blackwell Munksgaard 2004 Æ All rights reservedOral histoplasmosis associated with HIV infection:a comparative studyS. L. Herna´ndez1, S. A. Lo´pez de Blanc1,2, R. H. Sambuelli3,4, H. Roland3, C. Cornelli3, V. Lattanzi1,M. A. Carnelli41Clinical Stomatology B, School of Dentistry, National University of Co´rdoba, Co´rdoba; 2Department of Oral Pathol
Wissenschaftliche Publikationen in medizinischen Fachjournalen Ernst E, Weihmayr T, Matrai A, Resch KL. Changes in blood rheology of grossly obese individuals during a very low calorie diet. Int J Obes 1989;(Suppl2):167-8. Resch KL, Ernst E, Matrai A, Paulsen HF. Blutfließeigenschaften beeinflussen die Prognose nach Schlaganfall. Perfusion 1990;3:99-110. Resch KL, Ernst E, Matrai A, Schmid