Astrocytes in Alzheimer's disease gray matter express alpha 1-antichymotrypsin mRNA.

The serine protease inhibitor alpha 1-antichymotrypsin (ACT) has been shown to be tightly associated with the amyloid found in plaque cores and blood vessels in the brains of patients with Alzheimer's disease (AD). Although the ACT found in plaques could be derived from the high levels of ACT in serum, previous Northern analysis revealed that ACT mRNA is produced locally in AD gray matter at much higher levels than in control gray matter. To determine which brain cells express ACT mRNA, we conducted in situ hybridization with 35S-labeled cRNA probes on hippocampal sections from four AD and three control cases.

The beta-amyloid protein precursor of Alzheimer disease has soluble derivatives found in human brain and cerebrospinal fluid.

In this study, we use antisera to synthetic beta-amyloid protein precursor (beta APP) peptides to identify, in human brain and cerebrospinal fluid (CSF), soluble approximately 125- and approximately 105-kDa derivatives of the beta APP that lack the carboxyl terminus of the full-length, membrane-associated forms. We show that the soluble approximately 125-kDa beta APP derivative contains the Kunitz protease inhibitor domain, whereas the approximately 105-kDa form does not, and we confirm that these two proteins are soluble beta APP derivatives by purifying each from human CSF and directly sequencing its amino terminus.

Neurochemistry of dementia: establishing the links.

Neurochemical research in dementia needs to move beyond descriptive inventories of neurotransmitter systems affected in the specific disorders and to link to molecular studies of mechanism and clinical studies of cognition. New advances in Alzheimer's Disease (AD), Huntington's Disease (HD), and Parkinson's Disease (PD) are being guided by models of how nerve cells die in these disorders. Theories of pathophysiology which address the cellular level need to explain the selective vulnerability of neuronal populations in the different diseases.

Antisera to an amino-terminal peptide detect the amyloid protein precursor of Alzheimer's disease and recognize senile plaques.

The cerebral amyloid deposited in Alzheimer's disease (AD) contains a 4.2 kDa beta amyloid polypeptide (beta AP) that is derived from a larger beta amyloid protein precursor (beta APP). Three beta APP mRNAs encoding proteins of 695, 751, and 770 amino acids have previously been identified.

Amyloid protein precursor messenger RNAs: differential expression in Alzheimer's disease.

In situ hybridization was used to assess total amyloid protein precursor (APP) messenger RNA and the subset of APP mRNA containing the Kunitz protease inhibitor (KPI) insert in 11 Alzheimer's disease (AD) and 7 control brains. In AD, a significant twofold increase was observed in total APP mRNA in nucleus basalis and locus ceruleus neurons but not in hippocampal subicular neurons, neurons of the basis pontis, or occipital cortical neurons. The increase in total APP mRNA in locus ceruleus and nucleus basalis neurons was due exclusively to an increase in APP mRNA lacking the KPI domain.

In situ hybridization of nucleus basalis neurons shows increased beta-amyloid mRNA in Alzheimer disease.

To determine which cells within the brain produce beta-amyloid mRNA and to assess expression of the beta-amyloid gene in Alzheimer disease, we analyzed brain tissue from Alzheimer and control patients by in situ hybridization. Our results demonstrate that beta-amyloid mRNA is produced by neurons in the nucleus basalis of Meynert and cerebral cortex and that nucleus basalis perikarya from Alzheimer patients consistently hybridize more beta-amyloid probe than those from controls. These observations support the hypothesis that increased expression of the beta-amyloid gene plays an important role in the deposition of amyloid in the brains of patients with Alzheimer disease.

Effect of fibrillation on acetylcholinesterase mRNA in cultured embryonic rat myotubes.

Acetylcholinesterase (AChE) and AChE mRNA were evaluated in spontaneously fibrillating myotubes derived from 20-day-old rat fetuses and in matched cultures in which fibrillation was prevented by adding tetrodotoxin on the fourth day of culture. On the eighth day of culture, the AChE activity of fibrillating and nonfibrillating cultures was 5332 and 1861 pmol ACh hydrolyzed min-1 dish-1, respectively (P less than 0.005).

Molecular forms of acetylcholinesterases in Alzheimer's disease.

In this study, we examined 26 cases of Alzheimer's disease (AD) and 14 age-matched controls. In Brodmann area 21 cerebral cortex of the AD cases, there was no change in soluble G1 and G4 acetylcholinesterase (AChE) (EC 3.1.

Effect of fibrillation on the secretion of acetylcholinesterase from cultured embryonic rat myotubes.

We have measured acetylcholinesterase (AChE) turnover and secretion in spontaneously fibrillating rat myotubes and in cultures in which fibrillation was blocked with tetrodotoxin. The rate at which AChE appeared in the medium was 4 times greater in fibrillating than in non-fibrillating cultures. In a 2-h interval, 32% of the AChE in fibrillating myotubes and 26% of the AChE in non-fibrillating myotubes turned over.

Assembly of monomeric acetylcholinesterase into tetrameric and asymmetric forms.

A pulse-chase experiment was performed in embryonic rat myotube cultures to examine possible precursor-product relationships among the various molecular forms of acetylcholinesterase (AChE). AChE was labeled with paraoxon, a compound which diethylphosphorylates AChE at its active site. Diethylphosphorylated (labeled) AChE is inactive but can be reactivated by treatment with 1-methyl-2-hydroxyiminomethyl-pyridinium.

Turnover of acetylcholinesterase in innervated and denervated rat diaphragm.

The acetylcholinesterase (AChE) in rat diaphragms was labelled by intravenous injection of echothiophate in order to evaluate the turnover of AChE in innervated and denervated muscle in vivo. Echothiophate diethylphosphorylates AChE thereby inactivating it. Labelled (diethylphosphorylated) enzyme is rapidly and quantitatively reactivated with 1-methyl-2-hydroxyiminomethylpyridinium (2-PAM), so labelled (diethylphosphorylated) AChE was conveniently measured as 2-PAM-reactivatable AChE activity.

The effect of spontaneous electromechanical activity on the metabolism of acetylcholinesterase in cultured embryonic rat myotubes.

We have investigated the effect of electromechanical activity on the molecular forms of acetylcholinesterase (AChE) in cultured embryonic rat myotubes. Both globular and asymmetric forms of AChE are present on the 5th day of culture when myotubes are just beginning to fibrillate. Between days 5 and 8, the 4 S (G1), 10 S (G4), and 16 S (A12) forms increase dramatically, and appreciable 12.

Reduction in fever and symptoms in young adults with influenza A/Brazil/78 H1N1 infection after treatment with aspirin or amantadine.

During an outbreak of influenza A/Brazil/78 H1N1 infection, 47 volunteers with clinical and virological influenza of less than 2 days duration were treated in a randomized double-blind fashion for 5 days with 100 or 200 mg of amantadine daily or with 3.25 g of aspirin daily. The aspirin treatment group defervesced more rapidly (10.

Accelerated degradation of junctional acetylcholine receptor-alpha-bungarotoxin complexes in denervated rat diaphragm.

[125] alpha-bungarotoxin was administered to rats in vivo to label acetylcholine receptor in innervated diaphragm, 5-day denervated diaphragm, or diaphragm which had been denervated immediately before labeling. The rate of degradation of junctional toxin-receptor complexes was followed by sacrificing animals at various times after labeling. The rate of degradation of junctional toxin-receptor complexes was significantly faster in 5-day denervated left hemidiaphragm (t 1/2=2.

A transient increase in junctional acetylcholine receptors after denervation.

An improved method for assaying acetylcholine (ACh) receptors at the neuromuscular junction has been used to examine the effects of denervation in the rat diaphragm. An early increase of junctional ACh receptors occurred after two days of denervation followed by a decline at 14 days. Possible mechanisms responsible for this transient increase in junctional ACh receptors are discussed.

Spatial and temporal features of afferent inhibition of thalamocortical relay cells.

1. The temporal and spatial features of the afferent inhibition of thalamocortical relay (TCR) cells in the ventrobasal complex of the thalamus have been examined using paired conditioning and test air jets. 2.

Neural control of skeletal muscle cholinesterase: a study using organ-cultured rat muscle.

1. It has been proposed that the influence of innervation on the cholinesterase activity (ChE) of skeletal muscle and on end-plate ChE in particular is mediated by trophic substance(s) moved by axonal transport and released from nerve. We have tested this hypothesis using rat extensor digitorum longus (e.

Substances moved by axonal transport and released by nerve stimulation have an innervation-like effect on muscle.

Substances which have an innervation-like effect on the cholinesterase activity of organ-cultured rat extensor digitorum longus muscles are moved in nerve by axonal transport, are released from nerve by stimulation, and are present in innervated muscle but apparently absent from denervated muscle. Substances which increase the acetylcholine sensitivity of cultured muscles behave similarly.