New Pathways for the Skin's Stress Response: The Cholinergic Neuropeptide SLURP-1 Can Activate Mast Cells and Alter Cytokine Production in Mice.

The alpha7 nicotinic acetylcholine receptor (Chrna7) plays an essential anti-inflammatory role in immune homeostasis and was recently found on mast cells (MC). Psychosocial stress can trigger MC hyperactivation and increases pro-inflammatory cytokines in target tissues such as the skin. If the cholinergic system (CS) and Chrna7 ligands play a role in these cascades is largely unknown.

Commonalities and differences in extracellular levels of hippocampal acetylcholine and amino acid neurotransmitters during status epilepticus and subsequent epileptogenesis in two rat models of temporal lobe epilepsy.

Chemically or electrically induced status epilepticus (SE) in rodents is a commonly used method for induction of epilepsy. Structural and functional changes in the hippocampus play a pivotal role in epileptogenesis induced by SE. Although cholinergic mechanisms have long been thought to play an important role in the onset and propagation of epileptic seizures, not much is known about the potential role of acetylcholine (ACh) in ictogenesis and epileptogenesis in SE models of temporal lobe epilepsy.

Increased Cholinergic Response in α-Synuclein Transgenic Mice (h-α-synL62).

Pathological accumulation of misfolded α-synuclein (α-syn) in the brain plays a key role in the pathogenesis of Parkinson's disease, leading to neuronal dysfunction and motor disorders. The underlying mechanisms linking α-syn aggregations with neurotransmitter disturbance in Parkinson's brains are not well characterized. In the present study, we investigated transgenic mice expressing an aggregation-prone form of full-length human α-syn (h-α-synL62) linked to a signal sequence.

Microdialysis and its use in behavioural studies: Focus on acetylcholine.

Microdialysis is a technique that allows access to the extracellular space of many tissues. For behavioural studies, microdialysis probes are inserted into the brain under anesthesia, but the experiment can be done in awake and freely moving animals. Microdialysis is a sampling method (not a measuring method), therefore, the analyte(s) under study must be quantified from the dialysate using available analytical methods of high sensitivity.

Early metabolic responses to lithium/pilocarpine-induced status epilepticus in rat brain.

The lithium-pilocarpine model of status epilepticus is a well-known animal model of temporal lobe epilepsy. We combined this model with in vivo microdialysis to investigate energy metabolites and acute cellular membrane damage during seizure development. Rats were implanted with dialysis probes and pretreated with lithium chloride (127 mg/kg i.

Self-built microdialysis probes with improved recoveries of ATP and neuropeptides.

Background: Microdialysis is an established technique for collecting small molecular weight substances (e.g. neurotransmitter and energy metabolites) from the extracellular space.

Dynamics of hippocampal acetylcholine release during lithium-pilocarpine-induced status epilepticus in rats.

The lithium-pilocarpine model is a rat model of epilepsy that mimics status epilepticus in humans. Here, we report changes of acetylcholine (ACh) release in the hippocampus before, during and after status epilepticus as monitored by microdialysis in unanesthetized rats. Administration of pilocarpine (30 mg/kg s.

Phospholipase D is a target for inhibition of astroglial proliferation by ethanol.

The proliferation of astrocytes during early brain development is driven by growth factors and is accompanied by the activation of phospholipase D (PLD). Ethanol disrupts PLD signaling in astrocytes, a process which may contribute to delayed brain growth of fetuses exposed to alcohol during pregnancy. We here report that insulin-like growth factor 1 (IGF-1) is a strong mitogen for rat astrocytes (EC50 0.

Lipid membranes and beta-amyloid: a harmful connection.

Gradual changes in steady-state levels of beta amyloid peptides (Abeta) in the brain are considered as initial step in the amyloid cascade hypothesis of Alzheimer's disease (AD). Abeta is a product of the secretase cleavage of the amyloid precursor protein and there is evidence that the membrane lipid environment may modulate secretase activity and alters its function. Abeta disturbs membrane properties of artificial and isolated biological membranes and of plasma membranes in living cells.

Modulation of cholesterol, farnesylpyrophosphate, and geranylgeranylpyrophosphate in neuroblastoma SH-SY5Y-APP695 cells: impact on amyloid beta-protein production.

There is keen interest in the role of the isoprenoids farnesylpyrophosphate (FPP) and geranylgeranylpyrophosphate (GGPP) in protein prenylation and cell function in Alzheimer's disease (AD). We recently reported elevated FPP and GGPP brain levels and increased gene expression of FPP synthase (FPPS) and GGPP synthase (GGPPS) in the frontal cortex of AD patients. Cholesterol levels and gene expression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase were similar in AD and control samples, suggesting that homeostasis of FPP and GGPP but not cholesterol is specifically targeted in brain tissue of AD patients (Neurobiol Dis 2009 35:251-257).

Simple 2,4-diacylphloroglucinols as classic transient receptor potential-6 activators--identification of a novel pharmacophore.

The naturally occurring acylated phloroglucinol derivative hyperforin was recently identified as the first specific canonical transient receptor potential-6 (TRPC6) activator. Hyperforin is the major antidepressant component of St. John's wort, which mediates its antidepressant-like properties via TRPC6 channel activation.

Phenserine.

Phenserine, a derivative of physostigmine, was first described as an inhibitor of acetylcholinesterase (AChE) and was shown to improve cognition in various experimental paradigms in rodents and dogs. It was clinically tested for Alzheimer's disease, with moderate success in initial Phase II studies. Phenserine deserves attention for an additional quality of action: in addition to inhibiting AChE, it modulates the amount of beta-amyloid precursor protein (APP) in neuronal cell culture by reducing APP translation.

Hyperforin modifies neuronal membrane properties in vivo.

Hyperforin, the major active constituent of St. John Wort (SJW) extract, affects several neurotransmitter systems in the brain putatively by modulation of the physical state of neuronal membranes. Accordingly, we tested the effects of SJW extract and of hyperforin on the properties of murine brain membrane fluidity.

Brain-membrane cholesterol in Alzheimer's disease.

Cholesterol represents an important determinant of the physical state of biological membranes. Growing evidence indicate that changes in brain cholesterol and variations in neuronal membrane structure are involved in the development of Alzheimer's disease (AD). Cholesterol modulates the cleavage of the amyloid precursor protein and thus affect cellular production of beta-amyloid peptides (Ab).