266 research outputs found
Dysfunction of homeostatic control of dopamine by astrocytes in the developing prefrontal cortex leads to cognitive impairments
Astrocytes orchestrate neural development by powerfully coordinating synapse formation and function and, as such, may be critically involved in the pathogenesis of neurodevelopmental abnormalities and cognitive deficits commonly observed in psychiatric disorders. Here, we report the identification of a subset of cortical astrocytes that are competent for regulating dopamine (DA) homeostasis during postnatal development of the prefrontal cortex (PFC), allowing for optimal DA-mediated maturation of excitatory circuits. Such control of DA homeostasis occurs through the coordinated activity of astroglial vesicular monoamine transporter 2 (VMAT2) together with organic cation transporter 3 and monoamine oxidase type B, two key proteins for DA uptake and metabolism. Conditional deletion of VMAT2 in astrocytes postnatally produces loss of PFC DA homeostasis, leading to defective synaptic transmission and plasticity as well as impaired executive functions. Our findings show a novel role for PFC astrocytes in the DA modulation of cognitive performances with relevance to psychiatric disorders
Microtubule-associated protein 6 mediates neuronal connectivity through Semaphorin 3E-dependent signalling for axonal growth.
Structural microtubule associated proteins (MAPs) stabilize microtubules, a property that was thought to be essential for development, maintenance and function of neuronal circuits. However, deletion of the structural MAPs in mice does not lead to major neurodevelopment defects. Here we demonstrate a role for MAP6 in brain wiring that is independent of microtubule binding. We find that MAP6 deletion disrupts brain connectivity and is associated with a lack of post-commissural fornix fibres. MAP6 contributes to fornix development by regulating axonal elongation induced by Semaphorin 3E. We show that MAP6 acts downstream of receptor activation through a mechanism that requires a proline-rich domain distinct from its microtubule-stabilizing domains. We also show that MAP6 directly binds to SH3 domain proteins known to be involved in neurite extension and semaphorin function. We conclude that MAP6 is critical to interface guidance molecules with intracellular signalling effectors during the development of cerebral axon tracts
In vivo expression of polyglutamine-expanded huntingtin by mouse striatal astrocytes impairs glutamate transport: a correlation with Huntington's disease subjects
Huntington's disease (HD) is a neurodegenerative disorder previously thought to be of primary neuronal origin, despite ubiquitous expression of mutant huntingtin (mHtt). We tested the hypothesis that mHtt expressed in astrocytes may contribute to the pathogenesis of HD. To better understand the contribution of astrocytes in HD in vivo, we developed a novel mouse model using lentiviral vectors that results in selective expression of mHtt into striatal astrocytes. Astrocytes expressing mHtt developed a progressive phenotype of reactive astrocytes that was characterized by a marked decreased expression of both glutamate transporters, GLAST and GLT-1, and of glutamate uptake. These effects were associated with neuronal dysfunction, as observed by a reduction in DARPP-32 and NR2B expression. Parallel studies in brain samples from HD subjects revealed early glial fibrillary acidic protein expression in striatal astrocytes from Grade 0 HD cases. Astrogliosis was associated with morphological changes that increased with severity of disease, from Grades 0 through 4 and was more prominent in the putamen. Combined immunofluorescence showed co-localization of mHtt in astrocytes in all striatal HD specimens, inclusive of Grade 0 HD. Consistent with the findings from experimental mice, there was a significant grade-dependent decrease in striatal GLT-1 expression from HD subjects. These findings suggest that the presence of mHtt in astrocytes alters glial glutamate transport capacity early in the disease process and may contribute to HD pathogenesis
Search for Branons at LEP
We search, in the context of extra-dimension scenarios, for the possible
existence of brane fluctuations, called branons. Events with a single photon or
a single Z-boson and missing energy and momentum collected with the L3 detector
in e^+ e^- collisions at centre-of-mass energies sqrt{s}=189-209$ GeV are
analysed. No excess over the Standard Model expectations is found and a lower
limit at 95% confidence level of 103 GeV is derived for the mass of branons,
for a scenario with small brane tensions. Alternatively, under the assumption
of a light branon, brane tensions below 180 GeV are excluded
Search for Branons at LEP
We search, in the context of extra-dimension scenarios, for the possible
existence of brane fluctuations, called branons. Events with a single photon or
a single Z-boson and missing energy and momentum collected with the L3 detector
in e^+ e^- collisions at centre-of-mass energies sqrt{s}=189-209$ GeV are
analysed. No excess over the Standard Model expectations is found and a lower
limit at 95% confidence level of 103 GeV is derived for the mass of branons,
for a scenario with small brane tensions. Alternatively, under the assumption
of a light branon, brane tensions below 180 GeV are excluded
Measurement of Exclusive rho^0 rho^0 Production in Two-Photon Collisions at High Q^2 at LEP
Exclusive rho rho production in two-photon collisions involving a single
highly virtual photon is studied with data collected at LEP at centre-of-mass
energies 89GeV < \sqrt{s} < 209GeV with a total integrated luminosity of
854.7pb^-1 The cross section of the process gamma gamma^* -> rho rho is
determined as a function of the photon virtuality, Q^2 and the two-photon
centre-of-mass energy, Wgg, in the kinematic region: 1.2GeV^2 < Q^2 < 30GeV^2
and 1.1GeV < Wgg < 3GeV
Formation of the in Two-Photon Collisions at LEP
The two-photon width of the meson has been
measured with the L3 detector at LEP. The is studied in the decay
modes , KK, KK,
KK, , , and
using an integrated luminosity of 140 pb at GeV and
of 52 pb at GeV. The result is
(BR) keV. The dependence of the cross section is studied for
GeV. It is found to be better described by a Vector Meson
Dominance model form factor with a J-pole than with a -pole. In addition,
a signal of events is observed at the mass. Upper limits
for the two-photon widths of the , , and are also
given
Search for Charginos with a Small Mass Difference with the Lightest Supersymmetric Particle at \sqrt{s} = 189 GeV
A search for charginos nearly mass-degenerate with the lightest
supersymmetric particle is performed using the 176 pb^-1 of data collected at
189 GeV in 1998 with the L3 detector. Mass differences between the chargino and
the lightest supersymmetric particle below 4 GeV are considered. The presence
of a high transverse momentum photon is required to single out the signal from
the photon-photon interaction background. No evidence for charginos is found
and upper limits on the cross section for chargino pair production are set. For
the first time, in the case of heavy scalar leptons, chargino mass limits are
obtained for any \tilde{\chi}^{+-}_1 - \tilde{\chi}^0_1 mass difference
Direct Observation of Longitudinally Polarised W Bosons
The three different helicity states of W bosons, produced in the reaction
e+e- -> W+W- -> l nu q q~ are studied using leptonic and hadronic W decays at
sqrt{s}=183GeV and 189GeV. The W polarisation is also measured as a function of
the scattering angle between the W- and the direction of the e- beam. The
analysis demonstrates that W bosons are produced with all three helicities, the
longitudinal and the two transverse states. Combining the results from the two
center-of-mass energies and with leptonic and hadronic W decays, the fraction
of longitudinally polarised W bosons is measured to be 0.261 +/- 0.051(stat.)
+/- 0.016(syst.) in agreement with the expectation from the Standard Model
Search for Scalar Leptons in e+e- collisions at \sqrt{s}=189 GeV
We report the result of a search for scalar leptons in e+e- collisions at 189
GeV centre-of-mass energy at LEP. No evidence for such particles is found in a
data sample of 176 pb^{-1}. Improved upper limits are set on the production
cross sections for these new particles. New exclusion contours in the parameter
space of the Minimal Supersymmetric Standard Model are derived, as well as new
lower limits on the masses of these supersymmetric particles. Under the
assumptions of common gaugino and scalar masses at the GUT scale, we set an
absolute lower limit on the mass of the lightest scalar electron of 65.5 Ge
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