TP53INP1 exerts neuroprotection under ageing and Parkinson's disease-related stress condition.

TP53INP1 is a stress-induced protein, which acts as a dual positive regulator of transcription and of autophagy and whose deficiency has been linked with cancer and metabolic syndrome. Here, we addressed the unexplored role of TP53INP1 and of its Drosophila homolog dDOR in the maintenance of neuronal homeostasis under chronic stress, focusing on dopamine (DA) neurons under normal ageing- and Parkinson's disease (PD)-related context. Trp53inp1 mice displayed additional loss of DA neurons in the substantia nigra compared to wild-type (WT) mice, both with ageing and in a PD model based on targeted overexpression of α-synuclein.

Striatal molecular signature of subchronic subthalamic nucleus high frequency stimulation in parkinsonian rat.

This study addresses the molecular mechanisms underlying the action of subthalamic nucleus high frequency stimulation (STN-HFS) in the treatment of Parkinson's disease and its interaction with levodopa (L-DOPA), focusing on the striatum. Striatal gene expression profile was assessed in rats with nigral dopamine neuron lesion, either treated or not, using agilent microarrays and qPCR verification. The treatments consisted in anti-akinetic STN-HFS (5 days), chronic L-DOPA treatment inducing dyskinesia (LIDs) or the combination of the two treatments that exacerbated LIDs.

Mechanisms contributing to the phase-dependent regulation of neurogenesis by the novel antidepressant, agomelatine, in the adult rat hippocampus.

Agomelatine is a novel antidepressant acting as a melatonergic receptor agonist and serotonergic (5-HT(2C)) receptor antagonist. In adult rats, chronic agomelatine treatment enhanced cell proliferation and neurogenesis in the ventral hippocampus (VH), a region pertinent to mood disorders. This study compared the effects of agomelatine on cell proliferation, maturation, and survival and investigated the cellular mechanisms underlying these effects.

Plasma membrane expression of the neuronal glutamate transporter EAAC1 is regulated by glial factors: evidence for different regulatory pathways associated with neuronal maturation.

At the glutamatergic synapse the neurotransmitter is removed from the synaptic cleft by high affinity amino acid transporters located on neurons (EAAC1) and astrocytes (GLAST and GLT1), and a coordinated action of these cells is necessary in order to regulate glutamate extracellular concentration. We show here that treatment of neuronal cultures with glial soluble factors (GCM) is associated with a redistribution of EAAC1 and GLAST to the cell membrane and we analysed the effect of membrane cholesterol depletion on this regulation. In enriched neuronal culture (90% neurons and 10% astrocytes), GCM treatment for 10 days increases EAAC1 and GLAST cell surface expression with no change in total expression.

The neuronal excitatory amino acid transporter EAAC1/EAAT3: does it represent a major actor at the brain excitatory synapse?

EAAC1/EAAT3 is a transporter of glutamate (Glu) present at the post-synaptic neuronal element, in opposition to the two other main transporters, GLAST/EAAT1 and GLT1/EAAT2, expressed at the excitatory amino acid (EAA) synapse by surrounding astrocytes. Although, in the adult, EAAC1/EAAT3 exhibits a rather low expression level and is considered to make a minor contribution to Glu removal from the synapse, its early expression during brain development, before the astrocytes are functional, suggests that such a neuronal transporter is involved in the developmental effects of EAA and, possibly, in the biosynthesis and trophic role of GABA, which is excitatory in nature in different brain regions during the earlier stages of brain development. This neuronal Glu transporter is considered to have a dual action as it is apparently involved in the neuronal uptake of cysteine, which acts as a key substrate for the synthesis of glutathione, a major anti-oxidant, because the neurones do not express the Xc(-) transport system in the mature brain.

Glial soluble factors regulate the activity and expression of the neuronal glutamate transporter EAAC1: implication of cholesterol.

A co-ordinated regulation between neurons and astrocytes is essential for the control of extracellular glutamate concentration. Here, we have investigated the influence of astrocytes and glia-derived cholesterol on the regulation of glutamate transport in primary neuronal cultures from rat embryonic cortices. Glutamate uptake rate and expression of the neuronal glutamate transporter EAAC1 were low when neurons were grown without astrocytes and neurons were unable to clear extracellular glutamate.

Developmental expression and activity of high affinity glutamate transporters in rat cortical primary cultures.

The expression and activity of glutamate transporters (EAAC1, GLAST and GLT1) were examined during the development of cortical neuron-enriched cultures. Protein content and mitochondrial respiration both increased during the first 7 days, later stabilized and decreased from DIV14. Glutamate transport and extracellular concentration were relatively constant from DIV3 to 18.

Effects of PKA and PKC modulators on high affinity glutamate uptake in primary neuronal cell cultures from rat cerebral cortex.

In this study, the effects of various agents known to alter protein phosphorylation, via protein kinase C or A, on high affinity glutamate uptake were investigated in primary neuronal cell cultures of rat cerebral cortex. Incubating the culture dishes with chelerythrine or H89 (N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide), which inhibit PKC and PKA, respectively, dramatically decreased the glutamate uptake in a dose-dependent manner. Saturation kinetic analysis showed that chelerythrine and H89 decreased the Vmax (chelerythrine: -61%, P < 0.

Effects of sustained low-flow ischemia on myocardial function and calcium-regulating proteins in adult and senescent rat hearts.

Objective: Both aging and myocardial ischemia are associated with alterations of calcium-regulating proteins. We investigated the effects of graded levels of low-flow ischemia on myocardial function and on SR Ca(2+)-ATPase (SERCA2), Na(+)-Ca2+ exchanger (NCX) and ryanodine receptor (RyR2), at mRNA and protein levels in both adult and senescent myocardium.

Methods: Isolated hearts from 4 and 24 month old (mo) rats were retrogradely perfused during 180 min at 100% (100% CF, n = 11 and n = 11 respectively.

Senescent heart compared with pressure overload-induced hypertrophy.

Although systolic left ventricular (LV) function is normal in the elderly, aging is associated in rat papillary muscle with mechanical and sarcoplasmic reticulum Ca2+ ATPase alterations similar to those observed in the hypertrophied heart. However, alterations in the other calcium-regulating proteins implicated in contraction and relaxation are still unknown. To investigate alterations in LV function and calcium-regulating proteins, we measured hemodynamics and Na(+)-Ca2+ exchanger (NCx), ryanodine receptor (RyR2), and sarcoplasmic reticular Ca2+ ATPase (SERCA2) mRNA levels (expressed in densitometric scores normalized to that of poly(A+) mRNA) in left ventricle from 4-month-old (adult, n = 13) and 24-month-old (senescent, n = 15) rats.

Bioenergetic effects of repeated +Gz acceleration on rat heart: a 31P-NMR study on isolated hearts.

This investigation was designed to determine whether repeated exposure to high sustained +Gz acceleration induces persisting changes in the myocardial energetic metabolism. Rats were exposed to three plateaus of 30 s at 10 +Gz, four times a week, for 4 weeks. Myocardial concentrations of high-energy phosphorylated compounds were evaluated by 31P-nuclear magnetic resonance (NMR) spectroscopy on isolated hearts submitted to isovolumic aortic perfusion.

Energy metabolism patterns in mammalian myocardium adapted to chronic physiopathological conditions.

Objective: When the myocardium is subjected to a chronic overload, it enlarges and a major restructuring of all organelles and cellular functions occurs. The changes occurring at the level of the contractile apparatus are well documented; less is known about the alterations in the energy status of the hypertrophied cardiomyocyte. The purpose of this paper is firstly to provide a brief review of the data published on this topic and secondly to analyse previously published data drawn from studies devoted to the evaluation of the capacity of the ATP-producing processes to respond to an acute change in workload.

Alteration of cardiovascular function in trained rats fed with fish oil.

In vivo cardiovascular function of sedentary and exercise-trained rats were studied after a 3 week feeding period of diets containing either 10% fish oil, sunflower oil or lard. Rats were randomly assigned to six groups: fish oil diet: sedentary (FS), exercise-trained (FT); sunflower oil diet; sedentary (SS), exercise-trained (ST); lard diet: sedentary (LS), exercise-trained (LT). The exercised rats ran on a treadmill at a speed of 16 m/min, for 60 min/d, 7 days/week during 3 weeks.

Energy metabolism response to calcium activation in isolated rat hearts during development and regression of T3-induced hypertrophy.

The effect of calcium activation on energy production was investigated in isolated perfused hearts from rats treated with triiodothyronine (T3) during 15 days (0.2 mg/kg/day) and in hearts of rats allowed to recover after T3-treatment during 15 days. Changes in phosphorylated compound concentrations were followed in the isolated hearts perfused with a glucose-pyruvate medium by 31P-NMR spectroscopy, when the external calcium concentration was increased from 0.

Differential splicing of fibronectin pre-messenger ribonucleic acid during cardiac ontogeny and development of hypertrophy in the rat.

Background: Fibronectin, an extracellular matrix protein, exists as multiple isoforms expressed in a time- and cell-dependent manner. Since the developmental pattern of fibronectin expression has not been determined in the heart, the first issue of this study was to investigate the expression of total fibronectin mRNA as well as its isoforms during cardiac ontogeny. In adults, pressure overload induces a shift towards the fetal form of proteins expressed by either muscle or nonmuscle cardiac cells.

Alteration of cardiac energy state during development of hypertension in rats of the Lyon strain: a 31P-NMR study on the isolated rat heart.

The effect of different chronic blood pressure levels on cardiac energy metabolism was studied by 31P-NMR spectroscopy in perfused hearts from the Lyon strains of hypertensive (LH), normotensive (LN) and hypotensive (LL) rats at the ages of 12 and 21 weeks. The in vivo assessment of haemodynamic parameters measured at 21 weeks in anaesthetized rats with an ultraminiature catheter pressure transducer confirmed that left ventricular systolic pressure and mean aortic pressure were significantly greater (+25%) in LH rats than in LN and LL rats. In the LL animals, left ventricular systolic pressure was slightly reduced (-10%) and cardiac contractility (estimated by LV dP/dtmax) showed a 24% decreased compared to normotensive animals.

Effect of age on phosphorylated compounds and mechanical activity of isolated rat heart: a 31P-NMR study.

Objective: The aim was to test the hypothesis that aging may change the function and energetics of isolated hearts subjected to an increased work load induced by varying the calcium concentration ([Ca2+]) in the perfusion fluid from 0.5 to 1.0, 1.

Cardiovascular response to triiodothyronine in Sprague-Dawley and spontaneously hypertensive rats.

In this study we have compared the influence of triiodothyronine (T3) on cardiovascular function and heart weight in Sprague-Dawley and spontaneously hypertensive rats. We also investigated whether the effects induced by T3 are reversible. T3 was administered daily (0.

Function and energy metabolism of isolated hearts obtained from hyperthyroid spontaneously hypertensive rats (SHR). A 31P-nuclear magnetic resonance study.

It was the aim of this study to evaluate the effects of hyperthyroidism on heart function and cardiac energy metabolism of spontaneously hypertensive (SHR) rats. Hyperthyroidism was induced by daily injections of T3 (0.2 mg/kg s.

Energy metabolism of the hypertrophied heart studied by 31P nuclear magnetic resonance.

We report studies on the isolated hearts of rats treated with triiodothyronine (0.2 mg/kg daily) for 14 days, on spontaneously hypertensive rats (12 and 21 weeks old, Lyon strain) and on their respective controls. A 30% increase in cardiac weight was developed with triiodothyronine and a 40% increase in heart weight in the presence of spontaneous hypertension.

Phosphorylated compounds and function in isolated hearts: a 31P-NMR study.

The potential role of phosphorylated compounds in the control of myocardial cell respiration was investigated by means of 31P-nuclear magnetic resonance (NMR) spectroscopy. Isolated isovolumic rat hearts, perfused with a 9 mM glucose, 2 mM pyruvate medium at a constant beating rate (6 Hz) and temperature (37 degrees C), were subjected to changes in work load by varying the calcium concentration ([Ca2+]) in the perfusion fluid from 0.5 to 1.

Changes in heart function and cardiac cell size in rats with chronic myocardial infarction.

Myocardial infarctions were induced in rats by ligation of the left anterior descending (LAD) coronary artery. After 4 weeks, parameters of left (LV) and right ventricular (RV) function and of peripheral circulation were measured in the intact, anesthetized animals. The morphology of the heart chambers was examined at the macroscopic and cell size level.

Hypothermic preservation of the rat heart. Comparison of immersion and low-flow perfusion methods: contribution of 31P-NMR spectroscopy.

Comparison of rat heart preservation by simple storage in a cardioplegic solution at 4 degrees C (6 hr for group I; 15 hr for group II) and by hypothermic low-flow perfusion of the same solution (0.3 ml min-1, 15 hr: group III) was performed by measuring biochemical and functional parameters and by collecting 31P-NMR spectroscopy data. When compared to control values, adenine nucleotide levels remained unchanged in group I hearts, while glycogen was 45% hydrolyzed and lactate level increased by 700%.