Insulin reduces norepinephrine transporter mRNA in vivo in rat locus coeruleus

Acute and chronic in vitro insulin treatment can inhibit the uptake of norepinephrine (NE) by adult rat brain synaptosomes and slices, fetal neuronal cultures, and PC12 cells. In the present study we tested whether chronic in vivo insulin treatment could alter the biosynthetic capacity of rat locus coeruleus neurons for the NE transporter protein (NET). Chronic third ventricular insulin treatment resulted in a suppression of NET mRNA to about one third of the level of vehicle-treated controls. Our finding suggests that insulin may play a regulatory role in the synthesis of this transporter, thereby modulating activity in CNS noradrenergic pathways.     

Low‐concentrated acidic electrolysed water treatment of pork: inactivation of surface microbiota and changes in product quality

The study analysed the effect of low‐concentrated acidic electrolysed water (LCAEW) treatment on meat. Microbiological analysis and colour and sensory quality testing during storage were performed on Longissimus thoracis. FT‐IR and FT‐Raman spectroscopy were used to detect eventual changes in the structure of meat after treatment. Meat samples were sprayed for 120 s with LCAEW (0.001%, 0.01% or 0.1% NaCl solution were electrolysed for 0, 5 or 10 min). The highest reduction in total number of micro‐organisms (3.25 log reduction), yeast and moulds (2.68 log reduction) and psychrotrophs (3.10 log reduction) was observed after spraying the meat samples with 0.1% NaCl electrolysed for 10 min. LCAEW caused a decrease in deoxymyoglobin and metmyoglobin concentration in unstored meat samples. The preliminary sensory studies proved that colour changes are not significant for consumers. The IR and Raman spectra indicate that the structure of compounds of meat tissues are not affected by chlorine and chlorine compounds (LCAEW components). LCAEW has no influence on denaturation of meat protein.     

Glutamate potentiates the toxicity of mutant Cu/Zn-superoxide dismutase in motor neurons by postsynaptic calcium-dependent mechanisms

Mutations in the Cu/Zn-superoxide dismutase (SOD-1) gene are responsible for a subset of familial cases of amyotrophic lateral sclerosis. Using a primary culture model, we have demonstrated that normally nontoxic glutamatergic input, particularly via calcium-permeable AMPA/kainate receptors, is a major factor in the vulnerability of motor neurons to the toxicity of SOD-1 mutants. Wild-type and mutant (G41R, G93A, or N139K) human SOD-1 were expressed in motor neurons of dissociated cultures of murine spinal cord by intranuclear microinjection of plasmid expression vector. Both a general antagonist of AMPA/kainate receptors (CNQX) and a specific antagonist of calcium-permeable AMPA receptors (joro spider toxin) reduced formation of SOD-1 proteinaceous aggregates and prevented death of motor neurons expressing SOD-1 mutants. Partial protection was obtained by treatment with nifedipine, implicating Ca2+ entry through voltage-gated calcium channels as well as glutamate receptors in potentiating the toxicity of mutant SOD-1 in motor neurons. Dramatic neuroprotection was obtained by coexpressing the calcium-binding protein calbindin-D28k but not by increasing intracellular glutathione levels or treatment with the free radical spin trap agent, N-tert-butyl-alpha-phenylnitrone. Thus, generalized oxidative stress could have contributed in only a minor way to death of motor neurons expressing the mutant SOD-1. These studies demonstrated that the toxicity of these mutants is calcium-dependent and provide direct evidence that calcium entry during neurotransmission, coupled with deficiency of cytosolic calcium-binding proteins, is a major factor in the preferential vulnerability of motor neurons to disease.     

Intraventricular insulin enhances the meal-suppressive efficacy of intraventricular cholecystokinin octapeptide in the baboon.

Chronic intraventricular (IVT) insulin infusion suppresses food intake and body weight in the baboon. It has been hypothesized that one mechanism of this action may be enhancement of the effectiveness of satiety factors that regulate meal size. This hypothesis was supported by prior demonstration of a shift in the meal-suppressive effectiveness of cholecystokinin octapeptide (CCK-8) which was given intravenously. The authors tested the effectiveness of a near threshold dose of CCK-8 (25 ng/kg) given via the lateral ventricles (IVT) prior to a 30-min meal, while baboons were chronically infused with cerebrospinal fluid or insulin (100 μU/day) via the lateral ventricles. IVT CCK-8 infusion resulted in meal size changes of –44?±?7% and –75?±?9% in the absence and presence of insulin, respectively; this was observed in each of the three animals studied. These results provide further support for the hypothesis that IVT insulin can interact with other, meal-regulatory, peptides. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Up-regulation of protein chaperones preserves viability of cells expressing toxic Cu/Zn-superoxide dismutase mutants associated with amyotrophic lateral sclerosis

Mutations in the Cu/Zn-superoxide dismutase (SOD-1) gene underlie some familial cases of amyotrophic lateral sclerosis, a neurodegenerative disorder characterized by loss of cortical, brainstem, and spinal motor neurons. We present evidence that SOD-1 mutants alter the activity of molecular chaperones that aid in proper protein folding and targeting of abnormal proteins for degradation. In a cultured cell line (NIH 3T3), resistance to mutant SOD-1 toxicity correlated with increased overall chaperoning activity (measured by the ability of cytosolic extracts to prevent heat denaturation of catalase) as well as with up-regulation of individual chaperones/stress proteins. In transgenic mice expressing human SOD-1 with the G93A mutation, chaperoning activity was decreased in lumbar spinal cord but increased or unchanged in clinically unaffected tissues. Increasing the level of the stress-inducible chaperone 70-kDa heat shock protein by gene transfer reduced formation of mutant SOD-containing proteinaceous aggregates in cultured primary motor neurons expressing G93A SOD-1 and prolonged their survival. We propose that insufficiency of molecular chaperones may be directly involved in loss of motor neurons in this disease.     

Intraventricular Insulin and Leptin Reverse Place Preference Conditioned With High-Fat Diet in Rats.

The authors hypothesized that insulin and leptin, hormones that convey metabolic and energy balance status to the central nervous system (CNS), decrease the reward value of food, as assessed by conditioned place preference (CPP). CPP to high-fat diet was blocked in ad-lib fed rats given intraventricular insulin or leptin throughout training and test or acutely before the test. Insulin or leptin given only during the training period did not block CPP. Thus, elevated insulin and leptin do not prevent learning a food's reward value, but instead block its retrieval. Food-restricted rats receiving cerebrospinal fluid, insulin, or leptin had comparable CPPs. Results indicate that the CNS roles of insulin and leptin may include processes involving memory and reward. (PsycINFO Database Record (c) 2010 APA, all rights reserved)