Systemic Radical Scavenger Treatment of a Mouse Model of Rett Syndrome: Merits and Limitations of the Vitamin E Derivative Trolox.

Rett syndrome (RTT) is a severe neurodevelopmental disorder typically arising from spontaneous mutations in the X-chromosomal methyl-CpG binding protein 2 () gene. The almost exclusively female Rett patients show an apparently normal development during their first 6-18 months of life. Subsequently, cognitive- and motor-impairment, hand stereotypies, loss of learned skills, epilepsy and irregular breathing manifest.

Dopamine agonists rescue Aβ-induced LTP impairment by Src-family tyrosine kinases.

Soluble forms of oligomeric amyloid beta (AβO) are involved in the loss of synaptic plasticity and memory, especially in early phases of Alzheimer's disease. Stimulation of dopamine D1/D5 receptors (D1R/D5R) is known to increase surface expression of synaptic α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate subtype glutamate and N-methyl-D-aspartate subtype glutamate receptors and facilitates the induction of the late phase of long-term potentiation (LTP), probably via a related mechanism. In this study, we show that the D1/D5R agonist SKF38393 protects LTP of hippocampal CA1 synapses from the deleterious action of oligomeric amyloid beta.

Selective expression of a constitutively active erythropoietin receptor in GABAergic neurons alters hippocampal network properties without affecting cognition.

We have previously shown that treatment with erythropoietin (EPO) improves cognition in patients with neuropsychiatric disorders as well as in healthy mice, and that transgenic expression of a constitutively active form of the EPO receptor (cEPOR) in glutamatergic neurons boosts higher cognitive functions in mice. In the present work, we examined whether selective activation of EPOR signaling in GABAergic neurons would also modulate cognitive performance. We generated transgenic mice that express cEPOR under the control of the vesicular inhibitory amino acid transporter (Viaat) promoter and subjected them to comprehensive behavioral, cognitive, and electrophysiological analyses.

The free radical scavenger Trolox dampens neuronal hyperexcitability, reinstates synaptic plasticity, and improves hypoxia tolerance in a mouse model of Rett syndrome.

Rett syndrome (RS) causes severe cognitive impairment, loss of speech, epilepsy, and breathing disturbances with intermittent hypoxia. Also mitochondria are affected; a subunit of respiratory complex III is dysregulated, the inner mitochondrial membrane is leaking protons, and brain ATP levels seem reduced. Our recent assessment of mitochondrial function in MeCP2 (methyl-CpG-binding protein 2)-deficient mouse (Mecp2 (-) (/y)) hippocampus confirmed early metabolic alterations, an increased oxidative burden, and a more vulnerable cellular redox balance.

Oxidative burden and mitochondrial dysfunction in a mouse model of Rett syndrome.

Rett syndrome is an X chromosome-linked neurodevelopmental disorder associated with cognitive impairment, motor dysfunction and breathing irregularities causing intermittent hypoxia. Evidence for impaired mitochondrial function is also accumulating. A subunit of complex III is among the potentially dys-regulated genes, the inner mitochondrial membrane is leaking protons, brain ATP levels seem reduced, and Rett patient blood samples confirm increased oxidative damage.

Restraint Stress Intensifies Interstitial K(+) Accumulation during Severe Hypoxia.

Chronic stress affects neuronal networks by inducing dendritic retraction, modifying neuronal excitability and plasticity, and modulating glial cells. To elucidate the functional consequences of chronic stress for the hippocampal network, we submitted adult rats to daily restraint stress for 3 weeks (6 h/day). In acute hippocampal tissue slices of stressed rats, basal synaptic function and short-term plasticity at Schaffer collateral/CA1 neuron synapses were unchanged while long-term potentiation was markedly impaired.