Alzheimer and platelets: low-density platelet populations reveal increased serotonin content in Alzheimer type dementia.

Introduction: Alzheimer's disease (AD) is a progressive form of dementia characterized by an increase in the toxic substance β-amyloid in the brain. Platelets display a substantial heterogeneity with respect to density. They further contain a substantial amount of β-amyloid precursor protein.

Alpha-MSH rescues neurons from excitotoxic cell death.

This study investigates the effects of alpha-melanocyte-stimulating hormone (alpha-MSH), on neurodegeneration, gliosis and changes in the neurotrophic protein brain-derived neurotrophic factor (BDNF) and in pro-inflammatory cytokines, following kainic acid (KA)-induced excitotoxic damage in the rat. Male Sprague-Dawley rats were treated with alpha-MSH (intraperitoneally, i.p.

The influence of kainic acid on core temperature and cytokine levels in the brain.

Excitotoxic brain injury is associated with hyperthermia, and there are data showing beneficial effects of hypothermia on neurodegeneration and that hyperthermia facilitates the neurodegeneration. Cytokines are inflammatory proteins that seem to be involved in the neuroinflammation associated with epilepsy. Core temperature changes caused by the epileptogenic glutamate analogue kainic acid (KA) were investigated in relation to changes in levels of the pro-inflammatory cytokines interleukin-1beta (IL-1beta) and interleukin-6 (IL-6), and the endogenous interleukin-1 receptor antagonist (IL-1ra).

alpha-Melanocyte-stimulating hormone is neuroprotective in rat global cerebral ischemia.

The aim of the study was to investigate the effects of alpha-melanocyte-stimulating hormone (alpha-MSH), a tridecapeptide derived from proopiomelanocortin (POMC), on the neurodegeneration following global cerebral ischemia and reperfusion in the rat. The biological activities of alpha-MSH include inhibition of inflammatory responses and anti-pyretic effects. Male Sprague-Dawley rats were subjected to four-vessel occlusion (4-VO) global cerebral ischemia followed by reperfusion, and treated with alpha-MSH (intraperitoneally, i.

Cytokine production by a human microglial cell line: effects of beta-amyloid and alpha-melanocyte-stimulating hormone.

Senile plaques in the Alzheimer's disease (AD) are formed by aggregation of beta-amyloid (Abeta) peptide. Abeta peptide has been shown to activate microglia and stimulate their production of inflammatory factors, such as cytokines. In the AD brain, the continued presence of amyloid plaques may keep microglia persistently activated, leading to chronic inflammation in the CNS.

Alpha-MSH decreases core and brain temperature during global cerebral ischemia in rats.

A key pathological event during cerebral ischemia is the excitotoxic release of glutamate. We have shown previously that alpha-melanocyte-stimulating hormone (alpha-MSH) enhances the hypothermia induced by kainic acid. We have investigated the effects of systemic administration of alpha-MSH on four-vessel occlusion forebrain ischemia on core temperature (CT) and brain temperature (BT), respectively.

The novel guanidine ME10092 protects the heart during ischemia-reperfusion.

The novel guanidine N-(3,4-dimethoxy-2-chlorobenzylideneamino)-guanidine [ME10092; a metabolite to the strongly cardioprotective hydroxyguanidine N-(3,4-dimethoxy-2-chlorobenzylideneamino)-N'-hydroxyguanidine (PR5)] was administered intravenously to rats subjected to left coronary artery clamping followed by reperfusion. Administration of 1-10 mg/kg of ME10092 1 or 5 min before 10 min of coronary artery occlusion followed by 20 min reperfusion significantly and dose-dependently inhibited the reperfusion-induced burst of arrhythmia, and markedly improved the survival of the animals. This dose schedule also dose-dependently and significantly inhibited the ST-segment elevation seen on the ECG during the artery occlusion, and attenuated the secondary rise in ST-segment during the reperfusion.

Classification of G-protein coupled receptors by alignment-independent extraction of principal chemical properties of primary amino acid sequences.

We have developed an alignment-independent method for classification of G-protein coupled receptors (GPCRs) according to the principal chemical properties of their amino acid sequences. The method relies on a multivariate approach where the primary amino acid sequences are translated into vectors based on the principal physicochemical properties of the amino acids and transformation of the data into a uniform matrix by applying a modified autocross-covariance transform. The application of principal component analysis to a data set of 929 class A GPCRs showed a clear separation of the major classes of GPCRs.

Spinal cord morphology and antinociception after chronic intrathecal administration of excitatory amino acid antagonists in the rat.

Drugs that antagonize the action of excitatory amino acids on the NMDA receptor in the spinal cord are of interest in pain treatment. Before such drugs can be applied clinically, their potential toxicity should be studied. This study was performed in rats in order to reveal possible neurotoxicologic side effects following chronic intrathecal (i.

Intrathecal somatostatin in the guinea pig: effects on spinal cord blood flow, histopathology and motor function.

In the present investigation, the vasoconstrictive, motor and neurodegenerative effects of intrathecal somatostatin (SST) were assessed in guinea pigs implanted with lumbar intrathecal catheters. Five consecutive dose increments of SST (5, 10, 15, 30 and 60 micrograms) to a total of 120 micrograms during the period of 16 +/- 3 min, resulted in a moderate (< 20%), gradual decrease of the spinal blood flow monitored with the laser-doppler method. A subsequent injection of clonidine (50 micrograms) or norepinephrine (10 micrograms) resulted in a more pronounced decrease of spinal blood flow (35% and 79%, respectively).

Intrathecal and epidural somatostatin in rats: can antinociception, motor effects and neurotoxicity be separated?

In the present investigation, the antinociceptive, motor blocking and neurotoxic effects of intrathecal and epidural somatostatin (SST) were assessed in rats implanted with lumbar intrathecal and epidural catheters. The doses studied were 5, 7.5, 10, 12.

Antinociceptive and 'neurotoxic' actions of somatostatin in rat spinal cord after intrathecal administration.

In the present investigation, the antinociceptive effect of somatostatin (SST) was assessed after intrathecal injection in rats. It was found that the peptide caused antinociception, hind limb paralysis and neuronal damage of the spinal cord in a dose-dependent manner. The threshold dose for antinociception was lower (approximately 10 micrograms) than that (approximately 30 micrograms) giving rise to chronic motor impairment associated with necrotic changes and loss of an immunohistochemical marker for motoneurons in the spinal cord.