Biomedical subjects

G Forloni

Publications and source records attributed to G Forloni.

79 records · Page 5Linked to original sources

PubMed1984

In vitro and in vivo evidence for the existence of presynaptic muscarinic cholinergic receptors in the rat hippocampus.

The intrahippocampal injection of kainic acid cleared 50% of muscarinic receptors and favored the detection of a further 20% loss in hippocampal presynaptic muscarinic receptors produced by electrolytic lesion of the medial septal nucleus as determined by Scatchard analysis of the saturation isotherms of [3H]dexetimide binding. In accordance, a decrease of about 20% in the in vivo accumulation of [3H]dexetimide in the hippocampus was found in animals lesioned in the medial septal nucleus. This effect occurred at both the dose of 5 micrograms/kg and at the saturating dose of 100 micrograms/kg of [3H]dexetimide. The results suggest that the loss was due to decreased receptor number rather than decreased receptor affinity.

Animals↗

PubMed1981

Studies on the indirect feedback inhibition of cholinergic neurons triggered by oxotremorine in striatum.

Oxotremorine produced 30-75% increases in rat striatal acetylcholine content and 10-15% decreases in choline content at the subtremorogenic doses of 0.34-1.34 mumol/kg, without affecting choline acetyltransferase and acetylcholinesterase activities and the sodium-dependent high affinity uptake of choline. The increase in acetylcholine was blocked by atropine and by reserpine indicating that oxotremorine indirectly influences the intrinsic striatal cholinergic neurons through a monoamine-mediated negative feedback loop. Experiments designed to interfere with neurotransmitter function indicated that noradrenaline and not dopamine or serotonin, mediated the response to oxotremorine.

Acetylcholine↗

PubMedDate not supplied

Apoptosis-mediated neurotoxicity induced by beta-amyloid and PrP fragments.

The neurotoxic activity of beta-amyloid (beta A) and prion protein (PrP) fragments contributed to the hypothesis concerning a causal role of amyloid deposits in Alzheimer disease (AD) and in prion-related encephalopathies. In this study, we investigated some aspects of the molecular mechanisms associated with neurotoxic activity of synthetic peptides homologous to beta A (beta 25-35) or PrP (PrP106-126) fragments. Chronic (5-7 d) exposure to both peptides induced neuronal death by apoptosis, as suggested by biochemical and morphological analysis. The apoptotic mechanism was confirmed by ultrastructural examination. The intracellular cascade of events activated by peptides was investigated by Northern blot and PCR analysis of expression of early genes (c-fos, c-jun, c-myc) and other proteins (p53, SGP-2 bcl-2, HSP70, Ich-1) potentially involved in apoptosis. With the exception of bcl-2 mRNA decrease and a slight increase of SGP-2 in PrP106-126-treated cells, no consistent alterations of these mRNA expressions were found in neuronal cells exposed to beta 25-35 or PrP106-126. Furthermore, we synthesized amidated homologs of both peptides with low amyloidogenic activity to test directly the relationship between amyloid fibrils and cell death. The neurotoxicity exhibited by PrP106-126-NH2 was similar to that observed with original peptide, whereas the amidation of beta 25-35 partially reduced the neurotoxicity of this peptide.

Alzheimer Disease↗

PubMedDate not supplied

Intracellular mechanisms mediating the neuronal death and astrogliosis induced by the prion protein fragment 106-126.

Prion encephalopathies include fatal diseases of the central nervous system of men and animals characterized by nerve cell loss, glial proliferation and deposition of amyloid fibrils into the brain. During these diseases a cellular glycoprotein (the prion protein, PrP(C)) is converted, through a not yet completely clear mechanism, in an altered isoform (the prion scrapie, PrP(Sc)) that accumulates within the brain tissue by virtue of its resistance to the intracellular catabolism. PrP(Sc) is believed to be responsible for the neuronal loss that is observed in the prion disease. The PrP 106-126, a synthetic peptide that has been obtained from the amyloidogenic portion of the prion protein, represents a suitable model for studying the pathogenic role of the PrP(Sc), retaining, in vitro, some characteristics of the entire protein, such as the capability to aggregate in fibrils, and the neurotoxicity. In this work we present the results we have recently obtained regarding the action of the PrP 106-126 in different cellular models. We report that the PrP 106-126 induces proliferation of cortical astrocytes, as well as degeneration of primary cultures of cortical neurons or of neuroectodermal stable cell lines (GH(3) cells). In particular, these two opposite effects are mediated by the same attitude of the peptide to interact with the L-type calcium channels: in the astrocytes, the activity of these channels seems to be activated by PrP 106-126, while, in the cortical neurons and in the GH(3) cells, the same treatment causes a blockade of these channels causing a toxic effect.

Amino Acid Sequence↗

PubMedDate not supplied

Modulation of cerebellar CGRP binding sites induced by climbing fibre activation.

The neuropeptide CGRP is transiently expressed at neonatal stages in the rat olivocerebellar system, while high affinity binding sites for the peptide are permanently expressed in the molecular layer of the adult cerebellum. In this study, an increase in the density of cerebellar high affinity binding sites for calcitonin gene-related peptide (CGRP) is induced by harmaline, given at a dose appropriate to induce tremor. The present results, taken together with the demonstration that harmaline is a potent stimulator of the olivocerebellar system, suggest that the expression of cerebellar CGRP receptors can be modulated by the level of activity in the cerebellar afferents.

Animals↗

PubMedDate not supplied

Apolipoprotein E and intronic polymorphism of presenilin 1 and alpha-1-antichymotrypsin in Alzheimer's disease and vascular dementia.

Apolipoprotein E (ApoE) genotypes, presenilin 1 (PS-1) and alpha(1)-antichymotrypsin (ACT) polymorphism and the association of the genotypes were examined in patients with Alzheimer's disease (AD, n = 121) or vascular dementia (VD, n = 68) in comparison with elderly controls (n = 125). The frequency of the ApoE epsilon 4 allele was significantly increased both in late-onset AD (0.35) and in VD (0.17); the frequency of ApoE epsilon 2 was significantly reduced in AD, but it was similar in VD and controls. The presence of the allele 1 of PS-1 intronic polymorphism was not associated with AD or VD and was not influenced by the ApoE genotypes. Also, the frequency of allele A of the intronic polymorphism of ACT was similar in AD, VD and controls and it was not altered by ApoE or PS-1 genotypes. The results confirm the association between ApoE epsilon 4 and AD and indicate an increase in ApoE epsilon 4 in Vd, too. A potential protective role of ApoE epsilon 2 is also suggested for late-onset AD but not for VD. No association was shown between ACT allele A and PS-1 allele 1 in AD or VD.

Aged↗

PubMedDate not supplied

beta-Amyloid neurotoxicity.

beta-amyloid (beta A, 39-43 amino acids) deposition in brain parenchyma and vessel walls is a major pathological feature of Alzheimer's disease (AD). This is associated with degenerative changes of neuronal cell bodies and processes, and neuronal death. beta A, a portion of a larger transmembrane glycoprotein, has been reported to be toxic in several tissue culture models. The neurotoxic activity of beta A synthetic peptides is associated with their fibrillogenic capacity. However, in vivo studies on beta A neurotoxic activity have not proved conclusive and further investigations are necessary to establish the pathogenetic role of beta A in AD.

Alzheimer Disease↗