Biomedical subjects

N Angeretti

Publications and source records attributed to N Angeretti.

5 recordsLinked to original sources

PubMed1992

Decreased [3H]hemicholinium binding to high-affinity choline uptake sites in aged rat brain.

The binding of [3H]hemicholinium ([3H]HCh-3) to sodium-dependent high-affinity choline uptake sites provides a useful neuroanatomical and functional marker of the cholinergic system. We examined the autoradiographic distribution of [3H]HCh-3 binding sites in the forebrain of young (4-6 months) and old (32 months) rats. There was a widespread reduction of [3H]HCh-3 binding site density in the aged rat brain. This loss presented regional differences with maximal reduction in the medial and posterior striatum (55%) and in the dentate gyrus (47%), in limbic areas such as basolateral amygdala, tubercle olfactorium and piriform cortex the autoradiographic signal was about 25-30% lower. In aged hippocampus and cerebral cortex the density of [3H]HCh-3 binding sites was about 40% lower, the difference between young and senescent animals being less evident in the medial septum and basal nucleus. No significant alterations were observed in interpeduncular nucleus from old rats. These data are in agreement with the functional results obtained by measuring other cholinergic parameters in the aged rat and confirm the vulnerability of cholinergic system during aging.

Aging↗

PubMed1992

Chronic infusion of quinolinic acid in rat striatum: effects on discrete neuronal populations.

The intrastriatal infusion of relatively low doses of quinolinic acid (Quin, 4-10 nmol/h) for 1 or 2 weeks induced time-dependent degeneration of neuronal cells. We examined the effects of these infusions on discrete cellular populations. The distribution of somatostatin (SOM)-positive neurons labelled by immunocytochemistry or by NADPH-diaphorase histochemistry and of cholinergic cells stained by acetylcholinesterase was quantified in the peripheral portion of the lesioned area. SOM-positive cells did not appear selectively spared by Quin infusion. The proportion of SOM- and NADPH-diaphorase-positive neurons killed by exposure to Quin was similar to or higher than the percentage of total neurons degenerated (from 30 to 85%). A selective sparing of cholinergic cells was observed in all conditions examined; perfusion of 6 nmol/h for a week induced 65% of cell death while not more than 30% of cholinergic neurons were killed. Thus, the neurochemical similarity between the degenerative effects of intrastriatal Quin and Huntington's disease (HD) did not appear confirmed by the chronic perfusion of low doses of Quin for SOM-positive neurons, whereas an analogy between Quin's effects and HD was suggested by the pattern of AChE staining.

Acetylcholinesterase↗

PubMed1992

Expression of amyloid precursor protein mRNAs in endothelial, neuronal and glial cells: modulation by interleukin-1.

The origin of beta-amyloid deposited in senile plaques in Alzheimer's disease (AD) is not known. We compared the expression of protein precursor of beta-amyloid (APP) in the cell types involved in plaque formation. The levels of APP mRNA were determined in primary rat neurons and glial cells in culture, human endothelial cells and in a murine brain-derived endothelial cell line. Northern blot analysis was performed using an APP cDNA probe to detect the general APP sequence and an oligonucleotide (40 mer) complementary to the sequence of the Kunitz protease inhibitor (APP-KPI). The APP mRNA transcripts were abundant in all three cell types. The highest level of APP, normalized to beta-actin mRNA content, was expressed in neurons, followed by glial cells, where the APP expression was similar (94%) while in endothelial cells was lower (53%). The proportion between APP-KPI mRNA and total APP mRNA was high in endothelial, intermediate in glial and low in neuronal cells. We compared the effects of exposure to interleukin-1 (IL-1), a cytokine involved in several biological processes and elevated in AD, on APP mRNA expression in neuronal, glial and endothelial cells. In human endothelial and in brain-derived murine endothelial cells we observed a similar increase (50%) of total APP mRNA or APP-KPI mRNA after treatment with human recombinant IL-1 beta. In neuronal cells, IL-1 (200 ng/ml) substantially increased APP mRNA (175%), detected with both probes. In glial cells, the expression of APP mRNA did not appear to be altered by IL-1 (50-400 ng/ml). The results suggest a role of IL-1 in the neuronal mechanisms related to beta-amyloid protein deposition in AD.

Alzheimer Disease↗

PubMed1990

Decrease in [3H]hemicholinium binding to high-affinity choline uptake sites in deafferented striatum: restoration by oxiracetam.

Frontal cortical deafferentation of the rat striatum reduces the tone of striatal cholinergic neurons. We used biochemical and autoradiographic techniques to investigate whether the [3H]hemicholinium-3 ([3H]HCh-3) binding to sodium-dependent high-affinity choline uptake sites was influenced by this lesion. Frontal deafferentation produced a reduction of about 30% in the number of [3H]HCh-3 binding sites (Bmax) in striatum, with no significant changes in the binding affinity (Kd). Autoradiography showed a significant reduction of [3H]HCh-3 binding sites in the anteromedial portion of the striatum, but not in the posterior part of frontal deafferented rats. Oxiracetam (100 mg/kg), a nootropic drug, did not affect the distribution of [3H]HCh-3 binding sites in sham-operated rats but completely overcame the reduction in the number of [3H]HCh-3 binding sites in deafferented striatum.

Afferent Pathways↗

PubMed1990

Increased tryptophan hydroxylase mRNA in raphe serotonergic neurons spared by 5,7-dihydroxytryptamine.

Neurons expressing the tryptophan hydroxylase (TPH) mRNA within the raphe nuclei of control rats showed a distribution similar to that observed using an antibody for TPH. Numerous packed cells expressing the TPH mRNA were observed in the ventral and dorsal zone of the nucleus raphe dorsalis (NDR) and in the pars dorsalis of the nucleus centralis superior (NCS) whereas fewer and more scattered neurons were found in the pars medialis of NCS. Five days after the intracerebroventricular injection of 5,7-dihydroxytryptamine (5,7-DHT), which markedly reduced the serotonin (5-HT) content in the hippocampus, caudate putamen and cortex, the hybridization signal had completely disappeared in the dorsal region of the NDR. In the ventromedial region, above and between the medial longitudinal fasciculus (MLF), which includes the pars dorsalis of NCS, there was a partial decrease of cell number and a marked increase of the grain density over spared neurons. No significant change was noted in the number of TPH-positive cells and hybridization signal in individual neurons of the pars medialis of NCS. Consistent with previous evidence of increased TPH activity in the residual 5-HT terminals, the present study shows that synthesis of the TPH mRNA may be augmented in some neurons surviving the lesion.

5,7-Dihydroxytryptamine↗