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F Nicoletti

Publications and source records attributed to F Nicoletti.

At least 325 records · Page 18Linked to original sources
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Two sides of the same coin: Wnt signaling in neurodegeneration and neuro-oncology.

Wnts function through the activation of at least three intracellular signal transduction pathways, of which the canonical beta-catenin mediated pathway is the best understood. Aberrant canonical Wnt signaling has been involved in both neurodegeneration and cancer. An impairment of Wnt signals appears to be associated with aspects of neurodegenerative pathologies while overactivation of Wnt signaling is a common theme in several types of human tumors. Therefore, although therapeutic approaches aimed at modulating Wnt signaling in neurodegenerative and hyperproliferative diseases might impinge on the same molecular mechanisms, different pharmacological outcomes are required. Here we review recent developments on the understanding of the role of Wnt signaling in Alzheimer's disease and CNS tumors, and identify possible avenues for therapeutic intervention within a complex and multi-faceted signaling pathway.

Alzheimer Disease↗
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In vivo treatment with a monoclonal antibody to interferon-gamma neither affects the survival nor the incidence of lupus-nephritis in the MRL/lpr-lpr mouse.

The effects of the in vitro treatment with a mAb (DB-1) that neutralizes mouse IFN-gamma on the development of the SLE-like syndrome in MRL/lpr-lpr (MRL-lpr) mice were studied. The results show that the i.p. administration of 2.6 mg/week of DB-1 from the 12th to the 20th week of age neither affected the survival nor the incidence and severity of lupus nephritis in MRL-lpr mice. This study argues against the pathogenic relevance of IFN-gamma in this experimental model of human SLE.

Animals↗
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Dementia with Lewy bodies: a review.

The dementia with Lewy bodies (DLB) is the second major type of senile, degenerative dementia, after the Alzheimer disease (AD). It is characterized by the presence of cytoplasmic inclusions of alpha-synuclein in the cerebral cortex and in the nuclei of the brain stem. DLB patients frequently have complex visual hallucinations, depressive symptoms, Parkinsonian manifestations and cognitive deficits, showing important associations with the Parkinson disease and the AD. The DLB should be differentiated from atypical Parkinsonisms, but the differential diagnosis often remains difficult and unsafe. Clinical and neuropathological findings, as well as neuroimaging are valuable tools in establishing specific diagnosis of DLB. Acetylcholinesterase inhibitors, dopamine-agonists, benzodiazepines of short or medium half-life, and antidepressants may be useful in the treatment of DLB, depending on the dominant symptoms of the given patients.

Aged↗
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Comparative effects of estradiol benzoate, the antiestrogen clomiphene citrate, and the progestin medroxyprogesterone acetate on kainic acid-induced seizures in male and female rats.

We have investigated the comparative effects of estradiol benzoate (EB), the antiestrogen clomiphene citrate (CC), and the progestin medroxyprogesterone acetate (MPA) on seizures induced by systemic injection of kainic acid (15 mg/kg i.p.) in male and female rats. Subcutaneous administration for 10 days of EB (10 micrograms/kg) or high doses of CC (50 mg/kg) significantly potentiated kainate-induced seizures, with this effect being more pronounced in male animals. Doses of 2.5 mg/kg of CC potentiated kainate-induced seizures in male rats but were ineffective in female rats. Low doses of CC (0.5 mg/kg) exhibited a mild anticonvulsant effect in both sexes. Repeated administration of MPA (2.5 mg/kg) partially protected female animals against kainate-induced seizures; in male animals, MPA induced a 30% increase in the seizure severity score, although the difference from the score of control male rats was not significant. These data suggest that sex steroids influence kainate-induced seizures in a sex-dependent manner and that the effects of the antiestrogen CC are dose dependent. This should be taken into account in view of a possible use of CC and MPA in hormonal therapy for seizure disorders.

Animals↗
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Effects of CDP-choline administration on receptor-stimulated inositol phospholipid hydrolysis in brain slices and neuronal cultures.

Repeated addition of CDP-choline (100 microM, once a day since the 2nd day of maturation in culture) to corticostriatal neurons led to an increased basal hydrolysis of inositol phospholipids, as revealed by an enhanced formation of [3H]inositolmonophosphate ([3H]InsP) in the presence of 10 mM Li+. This increase was prevented by the muscarinic receptor antagonist, atropine, or by tetrodotoxin, but not by other receptor antagonists, such as L-2-amino-4-phosphonobutanoate (L-AP4), prazosin or ketanserin. The increase in inositol phospholipid hydrolysis induced by repeated addition of CDP-choline was obliterated when cultures were incubated in the presence of the muscarinic receptor agonist, carbamylcholine. CDP-choline had no effect on inositol phospholipid hydrolysis in cultured cerebellar neurons, which are devoid of cholinergic cells. The basal hydrolysis of inositol phospholipids was also increased in hippocampal slices prepared from rats repeatedly injected with CDP-choline (200 mg/kg, i.p. for 15 days). As observed in cultured cortico-striatal neurons, this increase was prevented by atropine and was masked in the presence of carabamylcholine. Taken collectively, these data indicate that repeated exposure to exogenous CDP-choline increases polyphosphoinositide turnover, an effect that results from an increased availability of acetylcholine acting on muscarinic receptors.

Acetylcholine↗
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Excitatory amino acids and neuronal plasticity: modulation of AMPA receptors as a novel substrate for the action of nootropic drugs.

The nootropic drug, aniracetam, behaves as a positive modulator of AMPA-sensitive glutamate receptors in a variety of systems, including intact brain tissue, amphibian oocytes injected with rat brain mRNA, and cultured neurons. In electrophysiological studies, aniracetam both increases the peak amplitude and reduces the rate of decay of the ion current generated by AMPA or quisqualate. In cultured neurons, aniracetam (as well as oxiracetam and piracetam) enhances the stimulation of 45Ca2+ influx produced by AMPA but not that produced by kainate or NMDA. In addition, aniracetam (as other nootropic drugs) increases the maximal density of low affinity binding sites for [3H]AMPA in crude synaptic membranes. Positive modulation of AMPA receptors by aniracetam provides a novel molecular substrate which explains the clinical efficacy of nootropic drugs as memory and cognition enhancers.

Amino Acids↗
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Inositol hexakisphosphate stimulates 45Ca2+ influx in purified mitochondria from rat liver.

Inositol hexakisphosphate (InsP6) stimulates 45Ca2+ influx in purified mitochondria from rat liver. The action of InsP6 is concentration-dependent, with an apparent EC50 value of 50 microM. Stimulation of 45Ca2+ influx may follow the interaction between InsP6 and specific membrane receptors. Accordingly, [3H]InsP6 binds to specific and saturable recognition sites in purified mitochondria. These results support the view that InsP6 acts as a signal molecule to regulate the intracellular homeostasis of Ca2+.

Animals↗
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Repeated injections of piracetam improve spatial learning and increase the stimulation of inositol phospholipid hydrolysis by excitatory amino acids in aged rats.

Repeated injections of piracetam (400 mg/kg, i.p. once a day for 15 days) to 16-month old rats led to an improved performance on an 8-arm radial maze, used as a test for spatial learning. This effect was accompanied by a greater ability of excitatory amino acids (ibotenate and glutamate) to stimulate [3H]inositol-monophosphate formation in hippocampal slices incubated in the presence of 10 mM Li+. Repeated administration of piracetam did not induce changes in excitatory amino acid-stimulated polyphosphoinositide hydrolysis in hippocampal slices prepared from 2-month old animals.

Animals↗
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Pyrrolidone-carboxylic acid magnesium salt (PCA-Mg2+) protects against seizures induced by excitatory amino acids.

Single administration of PCA-Mg2+ (200 mg/kg, s.c.) increased the latency and shortened the duration of seizures produced by systemic injection of N-methyl-D-aspartate (NMDA) in mice. Mortality was reduced in mice pretreated with PCA-Mg2+. Single or repeated (twice a day for 5 days) injections of PCA-Mg2+ (250 mg/kg, i.p.) also attenuated kainate-induced seizures in rats. However, PCA-Mg2+ had no effect on kainate-induced automatisms but reduced the frequency of generalized seizures. These results indicate that pharmacological doses of Mg2+ protect experimental animals against excitatory amino acid-induced seizures.

Animals↗
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Activation of excitatory amino acid receptors increases intracellular free [3H]arachidonate levels in cultured cerebellar neurons.

Addition of glutamate to cultured cerebellar neurons increases both intra- and extracellular content of [3H]arachidonic acid. The increase is time- and concentration-dependent and is antagonized by Mg2+ or by specific NMDA receptor antagonists (such as a-aminoadipate or MK-801). An increase in intracellular content of [3H]arachidonic acid is also induced by kainate and the muscarinic receptor agonist, carbamylcholine. However, as opposed to glutamate, carbamylcholine does not enhance the extracellular levels of [3H]arachidonic acid.

Animals↗
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Excitatory amino acid signal transduction in cerebellar cell cultures.

In primary cultures of cerebellar granule cells excitatory amino acid recognition sites are coupled with the stimulation of inositol phospholipid (PI) hydrolysis, cGMP formation and 45Ca2+ uptake. Mg2+, 2-amino-5-phosphonovalerate (APV) and phencyclidine (PCP) potently inhibit signal transduction in response to N-methyl-D-aspartate (NMDA), glutamate (GLU) and aspartate (ASP). Activation by quisqualate (QUIS) is transduced selectively into stimulation of PI hydrolysis and this response is not sensitive to inhibition by Mg2+, APV and PCP. Activation by kainate (KA) is transduced into potent stimulation of cGMP formation and 45Ca2+ uptake. Transduction of KA signal is not affected by Mg2+ and is relatively insensitive to PCP and APV.

Amino Acids↗
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[Physiopathological and clinical aspects of Parkinson disease. Current problems].

Some interpretative hypotheses of the most important symptoms of Parkinson's disease are formulated, on the ground of acquired neurohistopathologic elements and in the light of new observations of experimental neuro-physiology. The possible role of the inferior olivary body in the genesis of parkinsonian tremor is pointed out. The psycho-behavioural disorders and among these the severe weakness of pulsional control and the scanty elaboration of the affective-emotional motivation would be in relation, according to the Authors, to the involvement of the pallido-habenular pathways and the habenuloreticular midbrain outflow (limbic midbrain area).

Animals↗