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D Zaccheo

Publications and source records attributed to D Zaccheo.

At least 37 records · Page 2Linked to original sources
PubMed1997

Is amyloid beta-protein glycated in Alzheimer's disease?

Recent data suggest that protein glycation is involved in the process of amyloid formation in Alzheimer's disease (AD). To further investigate this issue, we analyzed the presence of advanced glycation end products (AGE) in soluble and insoluble forms of amyloid beta-protein (A beta) as well as in apolipoprotein E (apoE), a protein bound to amyloid deposits. Both proteins were extracted from cerebral cortex obtained from patients with AD and probed by immunoblotting with two antibodies specific for different AGE, already known to immunocytochemically label amyloid plaques. All the AGE antibodies failed to recognize either A beta or apoE, whereas they reacted with synthetic A beta glycated in vitro. These findings indicate that other proteins associated with amyloid deposits are candidates to be modified with AGE in Alzheimer's cerebral tissue.

Alzheimer Disease↗
PubMed1997

Muscarinic cholinergic receptor subtypes expression by human placenta.

The presence of a cholinergic system in the placenta is suggested by several data, but no information is available concerning cholinergic receptor expression by placenta. The present study was designed to investigate muscarinic cholinergic receptors in sections of human placenta using a radioligand binding techniques with [3H]N-methyl scopolamine ([3H]NMS) as a ligand. [3H]NMS was bound to sections of human placenta in a manner consistent with the labelling of muscarinic cholinergic receptors. The dissociation constant (Kd) value was 0.1 +/- 0.03 nM and the maximum density of binding site (Bmax) value was 10.82 +/- 0.09 fmol/mg of tissue. The binding was time-, temperature- and concentration-dependent, belonging to one class of high affinity sites. Analysis of [3H]NMS displacement curves by compounds acting on the different subtypes of muscarinic cholinergic receptor subtypes suggests that human placenta expresses the four subtypes (M1-M4) of muscarinic cholinergic receptor assayable with radioligand binding assay techniques. The demonstration of muscarinic cholinergic recognition sites in human placenta may contribute to define the possible significance of placental cholinergic system. Moreover, human placenta can be used as an easily obtainable human source of M1-M4 muscarinic cholinergic receptor subtypes.

Adult↗
PubMed1997

Muscarinic cholinergic receptors and acetylcholinesterase activity in umbilical artery and vein in pregnancy-induced hypertension (pre-eclampsia).

The influence of pregnancy-induced hypertension (pre-eclampsia) on muscarinic cholinergic receptors and on acetylcholinesterase (AChE) activity was investigated using frozen sections of the umbilical artery and vein. Pre-eclamptic patients undergoing Caesarean delivery and normotensive pregnant control woman undergoing Caesarean delivery with similar parity, gestation length and age were examined. Muscarinic cholinergic receptors were assayed in frozen sections of the umbilical artery and vein by a radioligand binding assay technique, using [3H]-N-methyl scopolamine (NMS) as a ligand. AChE was demonstrated with a histochemical technique associated with microdensitometry. [3H]-NMS was specifically bound to sections of both umbilical artery and vein in a manner consistent with the labelling of muscarinic cholinergic receptors. The affinity of the radioligand was similar in the two vessels, whereas the maximum density of binding sites (Bmax) was higher in the umbilical vein than in the artery. A faint AChE reactivity was observed in the tunica media of both umbilical artery and vein. In pre-eclampsia, a loss of [3H]-NMS binding sites not accompanied by changes in the affinity of radioligand was found. The decrease of muscarinic cholinergic receptors involved to a greater extent the umbilical artery than the vein. No differences in AChE activity were found at the level of umbilical artery and vein between control and pre-eclamptic subjects. These findings suggest that pre-eclampsia is characterized by a loss of muscarinic cholinergic receptors in the umbilical circulation not accompanied by changes of the acetylcholine catabolizing enzyme AChE. It is possible that the decreased density of vascular muscarinic cholinergic receptors in pregnancy-induced hypertension contribute to the increased resistance of the umbilical circulation occurring in pre-eclampsia.

Acetylcholinesterase↗
PubMed1996

Pharmacological characterization and autoradiographic localization of dopamine receptors in the rat adrenal medulla.

The pharmacological profile and the anatomical localization of dopamine D1-like and D2-like receptors were studied in sections of rat adrenal medulla, with radioligand binding and autoradiographic techniques, respectively. [3H]([R]-(+)-chloro-2,3,4,5-tetrahydro-5-phenyl-1 H-3benzazepin-al hemimaleate) (SCH 23390) was used as a ligand for dopamine D1-like receptors and [3H]spiperone was used as a ligand for dopamine D2-like receptors. Radioligand binding and light microscope autoradiography did not show specific [3H]SCH 23390 binding in sections of rat adrenal medulla. This suggests that rat adrenal medulla does not express dopamine D1-like receptors. [3H]Spiperone was specifically bound to sections of rat adrenal medulla. The binding was time-, temperature- and concentration-dependent, with a dissociation constant (Kd) of 1.05 nM and a maximum density of binding sites (Bmax) of 100.2 +/- 3.8 fmol/mg tissue. The pharmacological profile of [3H]spiperone binding to rat adrenal medulla was similar to that displayed by neostriatum, which is known to express dopamine D2 receptors. Light microscope autoradiography showed the accumulation of specifically bound [3H]spiperone as silver grains within sections of adrenal medulla. Silver grains were found primarily over the cellular membrane of chromaffin cells. The above data indicate that chromaffin cells of the rat adrenal medulla express dopamine receptors belonging to the dopamine D2 receptor subtype. These receptors are probably involved in the modulation of catecholamine release from chromaffin cells, as documented by functional studies.

Adrenal Medulla↗
PubMed1996

NADPH-diaphorase activity in brain macrophages during postnatal development in the rat.

NADPH-diaphorase histochemistry, that allows the visualization of cells producing the gaseous intercellular messenger nitric oxide, was used in the study of the forebrain during the first three postnatal weeks in the rat. Subpopulations of NADPH-diaphorase positive neurons were observed at all ages studied. In addition, non-neuronal NADPH-diaphorase-stained cells were detected in the subcortical white matter, and were very numerous in the supraventricular portion of the corpus callosum, and in the internal and external capsules. These cells were present during the first two postnatal weeks, and were especially prominent at the end of the first postnatal week. They were round-shaped and morphologically similar to the brain macrophages, whose phagocytic activity has been shown in previous studies to play a role in naturally occurring cell death and elimination of exhuberant axons. Series of sections adjacent to those stained with NADPH-diaphorase were processed with immunohistochemistry, using two different antibodies (OX-42 and ED-1) that detect macrophagic and microglial markers, and antibodies that recognize the neuronal form of nitric oxide synthase. Furthermore, brain sections from rats at postnatal day 7 were sequentially processed for either OX-42 or nitric oxide synthase immunohistochemistry followed by NADPH-diaphorase histochemistry. The morphological features and distribution of the non-neuronal NADPH-diaphorase-positive cells were superimposable to those obtained with OX-42 and ED-1 immunohistochemistry. In addition, these cells did not display nitric oxide synthase immunoreactivity. Double-labelled NADPH-diaphorase-positive and OX-42-immunoreactive cells were detected at postnatal day 7. The present results show that brain macrophages express NADPH-diaphorase activity during the early stages of the normal postnatal maturation and suggest that nitric oxide produced by brain macrophages could be involved in the development reshaping of the central nervous system.

Animals↗
PubMed1996

Isolated lung perfusion with platinum in the treatment of pulmonary metastases from soft tissue sarcomas.

A multimodality approach including operation and isolated lung perfusion with platinum was used in six patients with lung metastases from soft tissue sarcomas. Staged thoracotomies were used in two patients with bilateral lesions. The inclusion criteria generally applied for surgical excision were adopted in this study. The pulmonary artery and a portion of the left atrium were isolated from systemic circulation and cannulated. The cannulas were then connected to a perfusion circuit and normothermic isolated lung perfusion was done for 60 minutes. The lung was then flushed and metastasectomy was done. Serial blood (systemic and pulmonary), tissue (normal lung and tumor), and urine samples were obtained for platinum content measurement by flameless atomic absorption spectroscopy. Lung damage was assessed by light and electron microscopy examination and by serial respiratory tests. Isolated lung perfusion was accomplished in all patients without any death, operative complication, or systemic toxicity. After operation, interstitial and alveolar edema developed in two patients (48 hours after treatment), necessitating respiratory support in one case. Total platinum concentrations in pulmonary plasma were about 43 times greater than those in systemic plasma. No differences in platinum concentrations between normal lung and metastatic tissue were found. Thus the proposed isolated lung perfusion technique is feasible and safe enough to be offered as a valid model to study combined chemosurgical approaches in the treatment of lung metastases.

Adult↗
PubMed1996

Age-dependent changes in the expression of dopamine receptor subtypes in human peripheral blood lymphocytes.

The pharmacological profile and the density of dopamine D3 and D5 receptor subtypes expressed by human peripheral blood lymphocytes of subjects of different ages (ranging from 20 to 75 years) were assessed using radioligand binding techniques. Dopamine D3 receptor was assayed with [3H]7-hydroxy-N,N-di-n-propyl-2-aminotetraline ([3H]7-OH-DPAT) as a ligand. Dopamine D5 receptor was assayed using [3HIR]-(+)-(-chloro-2,3,4,5, tetrahydro-5-phenyl-1H-3-benzazepin-al-hemimaleate) ([3H]SCH 23390) as a ligand. The affinity and the pharmacological profile of [3H]7-OH-DPAT and [3H]SCH 23390 at dopamine D3 and D5 receptor, respectively, were similar in subjects of different ages. The density of dopamine D3 receptor binding sites was slightly decreased in subjects of 30-39 years in comparison with younger individuals. A remarkable loss of dopamine D3 receptor was then found between 40 and 49 years of age in comparison with younger subjects. A further slight decrease was noticeable between 50 and 59 years of age. The number of [3H]7-OH-DPAT binding sites was then stabilized after 60 years of age. The density of dopamine D5 receptor binding sites did not show age-dependent changes. The above findings indicate the occurrence of a decline in the density of lymphocyte dopamine D3 but not D5 receptor between adult and mature subjects. The possibility that dopamine D3 receptor assay in peripheral blood lymphocytes may represent a tool for investigating dopamine receptor function in aging and age-related neurological disorders is discussed.

Adult↗
PubMed1996

Presence of soluble amyloid beta-peptide precedes amyloid plaque formation in Down's syndrome.

Abnormal and excessive accumulation of the amyloid beta-peptide (A beta) in the brain is a major and common characteristic of all Alzheimer's disease (AD) forms irrespective of their genetic background. Insoluble aggregates of A beta are identified as amyloid plaques. These deposits are thought to form when the amount of A beta is increased in the brain parenchyma as a result of either overexpression or altered processing of the amyloid precursor protein (APP). Soluble A beta ending at carboxyl-terminal residue 40 (A beta 40) and, in lesser amount, the form ending at residue 42 (A beta 42), are normal products of the APP metabolism in cell cultures. Increased secretion of soluble A beta 42 has been observed in cells transfected with constructs modeling APP gene mutations of familial forms of AD (refs 4, 5). On the basis of these in vitro data it has been hypothesized that the presence of soluble A beta 42 plays a role in the formation of amyloid plaques. Subjects affected by Down's syndrome (DS) have an increased APP gene dosage and overexpress APP. Apparently because of this overexpression, they almost invariably develop amyloid deposits after the age of 30 years, although they are free of them at earlier ages. Moreover, it has been observed that A beta 42 precedes A beta 40 in the course of amyloid deposition in DS brain. Thus, DS subjects provide the opportunity to investigate in the human brain the metabolic conditions that precede the formation of the amyloid deposits. Here we report that soluble A beta 42 is present in the brains of DS-affected subjects aged from 21 gestational weeks to 61 years but it is undetectable in age-matched controls. It is argued that overexpression of APP leads specifically to A beta 42 increase and that the presence of the soluble A beta 42 is causally related to plaque formation in DS and, likely, in AD brains.

Adolescent↗
PubMed1995

Effect of long-term treatment with the dihydropyridine-type calcium channel blocker darodipine (PY 108-068) on the cerebral capillary network in aged rats.

The effects of treatment with the dihydropyridine Ca+2 antagonist darodipine (PY 108-068) on age-related changes in the cerebral capillary network was studied using alkaline phosphatase histochemistry with quantitative image analysis. The investigation was performed on male Wistar rats of 12 months (adult reference group) and 27 months. The 27-month-old rats consisted of two groups, the first of control untreated animals and the second of rats receiving an oral dose of 5 mg/kg/day of darodipine from the 21st to the 27th month. The cerebral areas examined included the frontal cortex, the occipital cortex, Ammon's horn of the hippocampus, and the dentate gyrus. The number and the average length of alkaline phosphatase-positive capillaries were decreased in old rats, when compared with adult rats. The intercapillary distance, which is considered as a sensitive parameter for capillary density was increased in aged rats in comparison to adult rats. The capillary diameter was increased slightly or unchanged in old rats. The Ammon's horn and the frontal cortex were the cerebral areas most affected by age-dependent changes of the capillary network. Treatment with darodipine increased the number and the average length of alkaline phosphatase-reactive capillaries and reduced the intercapillary distance and the diameter of cerebral capillaries in old rats. The pericapillary microenvironment of the Ammon's horn was the most sensitive to treatment with darodipine. The above results showed that treatment with darodipine is capable of counteracting some microvascular changes occurring in the brain of aged rats. This suggests that the blockade of dihydropyridine-type Ca2+ channels has a positive effect on the brain microvascular system and may counteract the impairment of pericapillary microenvironment occurring with aging.

Aging↗
PubMed1995

Effect of treatment with the dihydropyridine-type calcium antagonist darodipine (PY 108-068) on the expression of calbindin D-28K immunoreactivity in the cerebellar cortex of aged rats.

The influence of long term treatment with the dihydropyridine-type Ca2+ antagonist darodipine (PY 108-068) on age-dependent changes in calbindin D-28K immunoreactivity in the cerebellar cortex of male Wistar rats was assessed. In 12-month-old rats used as an adult reference group, specific calbindin D-28K immunoreactivity was found within the cytoplasm of Purkinje neurons and their dendritic processes. The number of Purkinje neurons displaying calbindin D-28K immunoreactivity was decreased in the cerebellar cortex of aged in comparison with adult rats. The pattern of calbindin D-28K immunoreactivity was similar in the cerebellar cortex of 24-month-old rats (aged), although a significant decrease in the intensity of immunoreactivity was noticeable. Treatment of aged rats with darodipine for 6 months increased the percentage of immunoreactive Purkinje neurons and the intensity of calbindin D-28K immunoreactivity in the cytoplasm of Purkinje neurons. Calbindin D-28K is a Ca2+ binding protein probably involved in the modulation of Ca2+ homeostasis. The observation of a positive effect of darodipine treatment on calbindin D-28K immunoreactivity in the cerebellar cortex suggests that manipulation of dihydropyridine-type Ca2+ channels may contribute to counter age-dependent changes of Ca2+ homeostasis.

Aging↗
PubMed1995

Identification of age-related changes of dopamine D1-like receptors in the rat cerebellar cortex.

The present study was designed to characterize the pharmacological profile of dopamine D1-like receptors in the rat cerebellar cortex and to assess if these receptor sites undergo age-related changes. Cerebella of young (3 months), adult (12 months), and old (27 months) male Wistar rats were examined by using radioligand binding techniques and light microscope autoradiography. The non-selective dopamine D1-like radioligand [3H]SCH 23390 was specifically bound to sections of rat cerebellum. The findings that dopamine displaced [3H]SCH 23390 binding in the submicromolar range suggest that labelling of a dopamine D5 (or D1B) receptor subtype. The affinity of [3H]SCH 23390 for dopamine D1-like receptors was similar in the cerebellar cortex of the three animal groups investigated, whereas radioligand binding techniques revealed a gradual age-related reduction of the density of binding sites. Light microscope autoradiography showed the localization of [3H]SCH 23390 binding sites primarily in the molecular layer and to a lesser extent in the Purkinje neuron layer of the cerebellar cortex. Aging was accompanied by a loss of [3H]SCH 23390 binding sites affecting mainly the molecular layer. The age-dependent loss of dopamine D1-like receptors is more pronounced if detected with radioligand binding techniques than with light microscope autoradiography. This suggests that the decrease of dopamine D1-like receptors observed in aging rat cerebellar cortex may depend in part on changes in the receptor expression and in part on cortico-cerebellar structural changes.

Age Factors↗
PubMed1995

Dopamine D1-like receptors in the thymus of aged rats: a radioligand binding and autoradiographic study.

Age-dependent changes in the density and pattern of dopamine D1-like receptors were studied in the thymus of young (3 months), adult (12 months) and aged (24 months) male Wistar rats using combined radioligand binding and autoradiographic techniques. [3H]SCH 23390, which was used as a ligand, was specifically bound to sections of the thymus in a manner consistent with the labelling of dopamine D5 receptor. The dissociation constant value was similar in the thymus of the three animal groups examined. The maximal density of binding sites, evaluated with conventional radioligand binding techniques, was significantly reduced in the thymus of adult in comparison with young rats and further reduced in aged animals. Silver grains which correspond to [3H]SCH 23390 binding sites were revealed by light microscope autoradiography primarily in the cortex of the thymus and in lesser amounts within thymic corpuscles. A progressive decrease in the density of silver grains more pronounced in the cortex than in thymic corpuscles was observed in the thymus of adult and old in comparison with young rats. The loss of silver grains revealed with autoradiography is more moderate than the decrease in the density of binding sites shown by radioligand binding. Silver grains developed per single cells (probably lymphocytes) of the thymic cortex were reduced between young and adult rats and further decreased in old rats. The above findings suggest that the age-related decline in the density of dopamine D5 receptor assayed in the thymus is due in part to the reduced thymic mass with aging.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1995

Differentiation of human trophoblast populations involves alterations in cytokeratin patterns.

Cytokeratins (CKs) are related to proliferation and differentiation of epithelial cells. Little knowledge exists about CK patterns in human trophoblast subpopulations (villous and extravillous trophoblasts). To better understand differentiation and function of trophoblast components, we studied the distribution patterns of CKs in the placenta throughout pregnancy. A panel of well-defined monoclonal antibodies against different types of cytokeratins, vimentin, and fibrin, was used on frozen and paraffin sections. CK8, 18, and 19 were expressed in all the villous and extravillous trophoblastic subsets throughout pregnancy. In the first trimester, syncytiotrophoblasts were positive for CK7 and 13 along the basal membrane. As pregnancy progressed there was an increase in intensity of the reaction product and a more diffuse positive staining of CK7 in the cytoplasm of the syncytium, with evident positivity along the apical membrane. CK13 showed similar expression as CK7, but with less intense staining along the apical membrane and less prominent staining in the cytoplasm. Villous cytotrophoblasts were also positive for CK7 and CK13. CK17 was found related to cytotrophoblastic cells in contact with or next to fibrin deposits. Extravillous cytotrophoblasts in cell islands and cell columns were positive for CK13 only in the cell layers located proximal to the villous stroma, whereas the distal and more differentiated cells were negative. CK7 was positive in all epithelial cells of cell islands and columns, but the reaction product was not present in cells deeply migrated into the decidua. Amnion was negative for anti-CK13 antibodies in the first trimester but was positive at term. CK4 and CK16 were not found in the placenta. Our study shows for the first time that the different populations of human placental trophoblast express cytokeratins in developmental, differentiative, and functional specific patterns. These findings can be useful to distinguish and classify the various trophoblastic populations and provide a foundation for studying pathological aspects of the trophoblast.

Cell Differentiation↗
PubMed1995

Localization of calcium channels of the L-type in human epicardial arteries: a light microscope autoradiographic study.

The anatomical localization of Ca2+ channels of the L-type was analyzed in sections of the human right and anterior interventricular coronary arteries by using in vitro light microscope autoradiography associated with radioligand binding techniques. [3H]Nicardipine was utilised as a ligand. Binding of the radioligand to sections of the two coronary arteries was time-, temperature- and concentration-dependent. Analysis of binding isotherms revealed a dissociation constant value of about 0.5 nM in the two arteries and maximum binding capacities of 139 +/- 6.4 fmol/mg tissue for the right coronary artery and of 173 +/- 9.5 for the anterior interventricular branch. The pharmacological profile of [3H]nicardipine binding to sections of human coronary arteries was consistent with the labelling of Ca2+ channels of the L-type. Dihydropyridine derivatives were the most powerful competitors of [3H]nicardipine binding, whereas phenylalkylamines, benzothiazepine or non-selective channel modulators were weak competitors or ineffective. Light microscope autoradiography revealed the highest density of [3H]nicardipine binding sites in the tunica media of the coronary arteries. In this layer Ca2+ channels of the L-type are located within smooth muscle cells. A lower accumulation of the radioligand occurred in the tunica adventitia, whereas no specific binding was found in the tunica intima. Study of the localization of Ca2+ channels in sections of human coronary arteries may contribute to a better understanding of the mechanism of the marked coronary dilatory activity elicited by Ca2+ antagonists demonstrable in both in vitro preparations and in vivo.

Adolescent↗
PubMed1995

Age-related changes in the density of muscarinic cholinergic M1 and M2 receptor subtypes in pyramidal neurons of the rat hippocampus.

Age-dependent changes in the expression of muscarinic M1 and M2 cholinergic receptors were assessed in the CA1 and CA3 fields of hippocampus using radioligand binding and autoradiographic techniques with [3H]-pirenzepine and [3H]-AF-DX 116 as ligands. Male Wistar rats of 2 months (young), 12 months (adult) and 27 months (old) of age were examined. Radioligand binding analysis revealed a significant decrease of the density of muscarinic M1 cholinergic receptors with increasing age and no change in muscarinic M2 cholinergic receptors. Autoradiographic evaluation of the number of silver grains developed within the cell body of pyramidal neurons of the CA1 and CA3 fields revealed a decrease of muscarinic M1 cholinergic receptors in the 27-month-old rats in comparison with younger cohorts and no changes in muscarinic M2 cholinergic receptors. These findings suggest that the reduction of muscarinic M1 sites noticed between rats of 2- and 12-months of age using radioligand binding techniques is probably dependent on the loss of hippocampal neurons rather than on the reduction of receptor density per neuron. Our data also indicate that appropriate morphological techniques associated with quantitative analysis may be useful in assessing age-dependent changes in the expression of neurotransmitter receptors by specific neuronal populations. The possible pharmaco-therapeutic relevance of the decreased expression of muscarinic M1 cholinergic receptors by pyramidal neurons of the hippocampus of old rats is discussed.

Aging↗
PubMed1995

Nucleus basalis magnocellularis lesions decrease histochemically reactive zinc stores in the rat brain: effect of choline alphoscerate treatment.

The effects of monolateral lesioning of the nucleus basalis magnocellularis (NBM) and of choline alphoscerate treatment on histochemically reactive vesicular zinc stores were assessed in the rat brain using the sulphide-silver histochemical technique. Histochemically reactive zinc stores are located primarily within association fibres of the neuropil of the cerebral cortex as well as in the mossy fibres of the hippocampus. The density of cortical and hippocampal sulphide-silver positive fibres, which might have a role in cognitive and mnemonic processes, parallels the density of zinc-containing presynaptic buttons. Unilateral lesions of NBM caused a remarkable decrease of sulphide-silver positive fibres from the 4th week after lesioning in the neuropil of the ipsilateral fronto-parietal cortex and from the 3rd week in the mossy fibres of the ipsilateral hippocampus. Treatment with choline alphoscerate, which is a precursor in the biosynthesis of brain phospholipids that increases the bioavailability of acetylcholine in the nervous tissue, restored, in part, the density and pattern of sulphide-silver positive fibres in the fronto-parietal cortex and in the hippocampus. The data suggest that, analogously to reports from Alzheimer's disease patients, lesions of the NBM cause a decrease of zinc stores in the rat brain. Choline alphoscerate treatment is able to counter the expression of this phenomenon which accompanies experimental lesions of the NBM.

Animals↗
PubMed1994

Muscarinic cholinergic receptors in the hippocampus of aged rats: influence of choline alphoscerate treatment.

The present study was designed to investigate age-dependent changes of muscarcinic M1 and M2 cholinergic receptors in the rat hippocampus using radioreceptor assay and autoradiographic techniques with [3H]pirenzepine and [3H]AF-DX 116 as ligands. The analysis was performed on 2-, 12- and 27-month-old male Wistar rats, considered young, adult and old, respectively. Moreover, the influence of a 6-month treatment with choline alphoscerate on the density and pattern of M1 and M2 cholinergic receptors was assessed. Choline alphoscerate (L-alpha-glyceryl phosphorylcholine) is a precursor in the biosynthesis of several brain phospholipids which increases the availability of acetylcholine in various tissues. Muscarinic M1 cholinergic receptors were significantly decreased with increasing age whereas M2 cholinergic receptors did not show changes. Choline alphoscerate treatment countered, in part, the loss of muscarinic M1 receptor sites in old rats. Light microscope autoradiography revealed a loss of silver grains developed after exposure of sections of hippocampus to [3H]pirenzepine in the stratum oriens of CA1 and CA3 fields in rats of 12 and 27 months in comparison with young animals. Choline alphoscerate restored, in part, the decrease of silver grains noted in old rats. Quantitative analysis of the density of silver grains developed in the cell body of pyramidal neurons of CA1 and CA3 fields processed for the demonstration of muscarinic M1 receptor sites revealed a decrease of these grains in rats of 27 months in comparison with younger cohorts. These findings suggest that the reduction in muscarinic M1 sites noticeable between 2- and 12-month rats is probably dependent on the loss of nerve cells and/or terminals in these hippocampal fields rather than to a reduction of their density per neuron. Treatment with choline alphoscerate increased the expression of muscarinic M1 cholinergic receptors within the cell body of pyramidal neurons of CA1 and CA3 fields compared to age-matched control old rats. Consistent with radioreceptor assay data, no changes in the density of muscarinic M2 cholinergic receptors in the animal groups examined were demonstrated by light microscope autoradiography. The possible pharmacological relevance of the increased expression of muscarinic M1 cholinergic receptors elicited by choline alphoscerate in the hippocampus of aged rats is discussed.

Aging↗