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Biomedical subjects

R Quirion

Publications and source records attributed to R Quirion.

At least 181 records · Page 10Linked to original sources
PubMed1994

Regulation of 1,4,5-IP3, 1,3,4,5-IP4 and IP6 binding sites following entorhinal cortex lesions in rat brain.

A lesion of the entorhinal cortex produces a loss of more than 80% of the synapses in the outer molecular layer of the hippocampus in the rat. However, this synaptic loss is transient. Beginning a few days after denervation, new synapses are formed, virtually replacing the lost inputs within two months. Synaptic remodelling induced by entorhinal cortex lesion is associated with specific modifications of various neurotransmitters, hormones and growth factors. Many of these substances act at membrane bound-receptors to induce the hydrolysis of phosphatidylinositols generating various inositol phosphates. Some of the key members of this family include inositol 1,4,5-trisphosphate, inositol 1,3,4,5-tetrakisphosphate and inositol hexakisphosphate which are all associated with the maintenance Ca2+ homeostasis. To investigate the potential roles and/or alterations of inositol phosphates in entorhinal cortex lesions-induced neuronal plasticity, we quantified specific receptor sites for inositol 1,4,5-trisphosphate, inositol 1,3,4,5-tetrakisphosphate and inositol hexakisphosphate using their respective tritiated ligands, at different periods post-lesion corresponding to the degenerative and subsequent reinnervation phases. [3H]inositol 1,4,5-trisphosphate binding sites are maximally increased (30%) between two and eight days post-lesion in the hippocampal formation on both sides of the lesion. In the cortex, [3H]inositol 1,4,5-trisphosphate binding increased also bilaterally following the lesion. Changes in [3H]inositol 1,3,4,5-tetrakisphosphate binding are delayed and reduced (20% increase) in magnitude compared to these seen for [3H]inositol 1,4,5-trisphosphate binding. The maximal peak in [3H]inositol 1,3,4,5-tetrakisphosphate binding is observed between eight and 14 days after the lesion in the hippocampal formation and the cortex.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

The distribution of somatostatin binding sites in the brain of gymnotiform fish, Apteronotus leptorhynchus.

The neuropeptide somatostatin (SS) and its binding sites display a wide distribution in the central nervous system of vertebrates. By employing semi-quantitative autoradiography, we identified such binding sites in the brain of the weakly electric fish Apteronotus leptorhynchus (Gymnotiformes, Teleostei). Whereas (SS1) binding sites for the octapeptide analogue Tyr3-SMS-201-995 appear to be absent in the gymnotiform brain, (SS2) binding sites for the analogue [Tyr0-D-Trp8]-somatostatin-14 were found in many brain regions and showed a similar distribution to that observed by other authors in the amphibian and mammalian central nervous system. Telencephalon While binding in the ventral telencephalon was typically low, all cell groups of the dorsal portion displayed a high degree of binding. The highest density of binding sites was found in the dorsal and caudal subdivision 2 of the dorsomedial telencephalon. Diencephalon Many cell groups of the diencephalon showed a medium to high degree of binding density. The highest level was seen in the habenula. Mesencephalon All layers of the optic tectum contained a medium number of binding sites, except the stratum marginale. In the torus semicircularis, the different layers displayed distinct binding density. While laminae 7-8 showed the highest degree of binding, the lowest density was found in lamina 6. Rhombencephalon Binding was generally low or absent in the tegmentum. Low levels of binding density were observed in the electrosensory lateral line lobe. Cerebellum Extremely high levels of binding were found in the eminentia granularis medialis and the eminentia granularis posterior. Throughout most regions of the brain, the relative density of binding sites and the relative amount of somatostatin immunoreactivity in fibres, as determined in previous studies, were in good agreement.

Animals↗
PubMed1994

The distribution of tachykinin binding sites in the brain of an electric fish (Apteronotus leptorhynchus).

We mapped the distribution of tachykinin binding sites utilizing quantitative autoradiography of iodinated substance P and eledoisin as prototypic ligands for neurokinin-1 (NK1) and neurokinin-3 (NK3) receptors, respectively. The two ligands produced highly heterogenous and quantitatively different patterns of specific binding, suggesting that they revealed different tachykinin receptor subtypes. Although [125I]substance P and [125I]eledoisin binding were correlated in most brain regions, the binding of substance P was usually denser. [125I]substance P binding and substance P-like immunoreactivity were reasonably correlated in most brain areas, although discrepancies were found in some nuclei. Dense [125I]substance P binding was found in most areas of the subpallium and in parts of the pallium related to the olfactory system, as well as in the glomerular layer of the olfactory bulb. Moderate to dense binding of both ligands was observed in preoptic area, hypothalamus, habenula, parts of the thalamus and preglomerular complex. Especially noteworthy was the presence of [125I] substance P binding in the diencephalic prepacemaker nucleus, a region involved in the control of electroncommuncatory behavior. Substance P-like immunoreactivity is sexually dimorphic in certain diencephalic nuclei, including the prepacemaker nucleus (Weld and Maler, 1992); no obvious difference was seen between [125I]substance P or [125I]eledoisin binding in the brains of male versus female fish. In the mesencephalon striking laminar patterns of binding were seen in the torus semicircularis dorsalis and the optic tectum. Dense binding was also noted in the raphé nuclei, the locus ceruleus and the sensory nucleus of the vagus. Although binding of substance P in the electrosensory lateral line lobe and nucleus preeminentialis was light, it was distributed in a discrete fashion, suggesting a role of substance P in electrosensory processing.

Amino Acid Sequence↗
PubMed1994

Blockade of neurotensin binding in the rat hypothalamus and of the central action of neurotensin on the hypothalamic-pituitary-adrenal axis with non-peptide receptor antagonists.

Central administration of neurotensin (NT) has been shown to activate the hypothalamic-pituitary-adrenal axis, an effect which seems dependent upon the release of corticotropin-releasing factor. In this study, we describe the distribution of NT binding sites in the hypothalamus using film and emulsion receptor autoradiography. Among the 125I-NT-labelled hypothalamic nuclei, relatively high densities of neurotensin binding sites were detected over the paraventricular nucleus. Silver grains on emulsion-coated slides overlaid indiscriminately cell bodies and surrounding processes of magnocellular and parvocellular parts of the nucleus. Two newly developed NT receptor antagonists, SR 48692 and its analog SR 48450, competed for 125I-NT binding to hypothalamic tissue sections and membrane preparations with Ki values in the nanomolar range. Moreover, intracerebrally injected SR 48450 was able to block the NT-induced hypothalamic-pituitary-adrenal axis activation in freely moving rats, whereas its administration alone did not significantly affect basal plasma levels of adrenocorticotropin and corticosterone. These data provide anatomical substrate for a potential neurotensin action at the hypothalamus in the hypothalamic-pituitary-adrenal axis activation and highlight the use of new non-peptide NT receptor antagonists to characterize the effects of NT on neuroendrocrine functions.

Adrenocorticotropic Hormone↗
PubMed1994

Hypothalamic-pituitary-adrenal activity during chronic central administration of interleukin-2.

The cytokine interleukin-2 (IL-2) exerts numerous effects within the immune as well as the central nervous system and is thought to serve as a humoral signal in their communication. Brain-derived or blood-borne IL-2 may also control the activity of the hypothalamic-pituitary-adrenal (HPA) axis at various levels of regulation. In this study we investigated whether persistently elevated levels of central IL-2, which are associated with several diseases or induced during immunotherapeutic use of this cytokine, could induce long term activation of the HPA axis. Adult male Sprague-Dawley rats received an intracerebroventricular infusion of the recombinant cytokine at a rate of 5 U/h (equivalent to 2.5 ng/h or 162 fmol/h) by means of osmotic minipumps. Control animals received heat-inactivated IL-2. After 7 days of continuous infusion, blood samples were taken at intervals of 4 h over a period of 24 h, and plasma levels of ACTH and corticosterone (CORT) were determined. IL-2 caused a significant increase in ACTH levels during the later portion of the dark phase of the cycle. Plasma CORT concentrations were significantly elevated over almost the whole diurnal cycle. Measurements of CORT-binding globulin concentrations revealed IL-2-induced decreases during the dark phase, resulting in a marked increase in free CORT. Additionally, after 11 days of chronic infusion, both groups of animals underwent a 20-min restraint stress. IL-2-treated animals showed stress-induced increases in plasma ACTH and CORT that were not significantly different from those of animals treated with heat-inactivated IL-2. Along with the alteration of HPA activity seen in the IL-2-treated animals, chronic delivery of the cytokine caused periventricular tissue damage and gliosis. Taken together, the data reflect the capacity of IL-2 to modulate neuroendocrine activity over an extended period of treatment. Moreover, the IL-2-induced effects on HPA activity seen here may help to explain some of the endocrine disturbances seen in patients undergoing IL-2 immunotherapy.

Adrenocorticotropic Hormone↗
PubMed1994

Autoradiographic distribution and receptor binding profile of [125I]Bolton Hunter-rat amylin binding sites in the rat brain.

Amylin is a recently isolated peptide from amyloid plaques in noninsulin-dependent diabetic patients and showed high sequence homology with calcitonin gene-related peptide. We investigated the distribution and the binding profile of [125I]Bolton Hunter-rat amylin ([125I]BH-rat amylin) binding sites in the rat brain, as well as the affinity of rat amylin for [125I]hCGRP alpha binding sites in the brain, atrium (CGRP1 receptor-enriched tissue) and vas deferens (CGRP2 receptor-enriched tissue). High amounts of high affinity [125I]BH-rat amylin binding sites were observed in the nucleus accumbens, various hypothalamic nuclei, amygdaloid body, dorsal raphe, tegmental and parabrachial nuclei and the locus ceruleus. Interestingly, both rat amylin and salmon calcitonin revealed low nanomolar affinities (2-19 nM) for [125I] BH-rat amylin binding sites in the various brain areas, whereas human calcitonin gene-related peptide-alpha (hCGRP alpha) showed lower affinities ranging between 13 to 150 nM. Moreover, the affinity of rat amylin was much lower than that of hCGRP alpha for [125I]hCGRP alpha binding in the brain, atrium and vas deferens, except for very few areas such as the nucleus accumbens and ventral striatum. Similarly, rat amylin was much weaker (100- to 400-fold) than hCGRP alpha to induce a biological effect in the atrium and vas deferens. These results thus suggest the existence of unique [125I]BH-rat amylin binding sites in the rat brain as well as limited cross-reactivity between rat amylin and [125I]hCGRP alpha receptors present in the brain, atrium and vas deferens.

Amyloid↗
PubMed1994

Multiple cholinergic markers are unexpectedly not altered in the rat dentate gyrus following entorhinal cortex lesions.

Since major cholinergic deficits are observed in Alzheimer's disease, the development of models to study possible cholinergic plasticity has generated great interest. In this regard, it has been shown that lesions of the entorhinal cortex, which sends glutamatergic projections to the hippocampus, promote the sprouting and plasticity of presumptive cholinergic septohippocampal fibers in the dentate gyrus, as revealed by AChE histochemistry. This sprouting was reported to be evident at 8 d and up to 30 d postlesion (DPL) and is now widely used as a model of cholinergic neuronal plasticity. In the present study, unilateral lesions of the entorhinal cortex were made in adult rats, and the status of various putative pre- and postsynaptic cholinergic markers was assessed after 2, 4, 8, 14, and 30 DPL. As expected, AChE was increased in the outer molecular layer of the ipsilateral dentate gyrus from 8 to 30 DPL. In contrast, the activity of ChAT, the enzyme responsible for the synthesis of ACh, and the densities of specific binding sites for 3H-AH5 183/vesamicol (blocker of the ACh vesicular transport sites), 3H-hemicholinium-3 (blocker of the high-affinity choline uptake sites), muscarinic-M2 (3H-AF-DX 384 and 3H-ACh), muscarinic-M1 (3H-pirenzepine), and nicotinic (3H-N-methylcarbamylcholine) cholinergic receptors were not increased on the ipsilateral molecular layer of the dentate gyrus, as compared to their contralateral controls. We conclude that the increase in AChE staining in the molecular layer of the dentate gyrus following entorhinal cortex lesions may be due to changes in noncholinergic neurons.

Acetylcholine↗
PubMed1994

Binding profile of a selective calcitonin gene-related peptide (CGRP) receptor antagonist ligand, [125I-Tyr]hCGRP8-37, in rat brain and peripheral tissues.

The calcitonin gene-related peptide (CGRP) C-terminal fragment human CGRP8-37 acts as a potent antagonist of various in vitro and in vivo effects of CGRP. Its iodinated counterpart, [125I-Tyr] hCGRP8-37, binds with high affinity (KD values between 7.5 x 10(-11)-2.1 x 10(-10) M) to what is apparently a single class of CGRP receptors in brain, atrium and vas deferens membrane preparations. The relative potencies of various CGRP-related fragments and analogs in competing for [125I-Tyr]hCGRP8-37 binding sites were similar in these three preparations, with hCGRP alpha being the most potent competitor, followed by unlabeled hCGRP8-37, the linear agonist [acetamidomethyl-cysteine2,7] hCGRP alpha, and finally by rat amylin-amide and salmon calcitonin. Competition profiles suggested the existence of a single affinity site (except in the case of hCGRP alpha, for which competition binding data were best fitted to two apparent affinity constants in all three tissues), whereas rat amylin-amide revealed two affinity constants in the rat brain. Guanylylimidodiphosphate (100 microM) failed to alter specific [125I-Tyr]hCGRP8-37 binding in the various tissues studied here. Quantitative receptor autoradiography in the rat brain revealed [125I-Tyr]hCGRP8-37 binding sites mostly concentrated in the nucleus accumbens (shell), caudate putamen (tail), amygdaloid body, pontine nuclei, cerebellum and inferior olive, whereas lower quantities of sites were present in the olfactory tubercle, nucleus accumbens (core), medial geniculate, superior colliculus, temporal cortex, inferior colliculus, lateral lemniscus, vestibular nuclei and principal sensory trigeminal nucleus.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Conformational and biological studies of neuropeptide Y analogs containing structural alterations.

We evaluated the alpha-helix content, the biological activities and the affinities of a series of neuropeptide Y (NPY) analogs containing structural alterations, mainly in the central portion of the molecule for which a putative alpha-helix arrangement has been proposed. First, we investigated the conformational and pharmacological characteristics of derivatives containing the N-terminal tetrapeptide linked to C-terminal peptide-amide segments of various lengths. In some of these, the missing portion was replaced with epsilon-aminocaproic acid, a flexible arm-linker. Data revealed that (1-4)-Aca-(18-36)NPY is a discontinuous analog almost as potent as the native peptide in a pharmacological preparation enriched in Y2 receptors (rat vas deferens), whereas it is about 5 times less potent in a Y1 bioassay (rabbit saphenous vein). This analog showed a similar profile in [125I]PYY binding assays performed in rat frontoparietal cortex (Y1) and hippocampus (Y2) membrane preparations. In a series of truncated derivatives obtained with the successive removal of the 5-13 to 5-17 segments of the NPY molecule, no apparent correlation was observed between the affinity or potency in bioassays and the alpha-helix content, as measured by circular dichroism spectroscopy. Other truncated analogs, obtained by linking the C-terminal 31-36 fragment to various N-terminal tetrapeptides were also investigated. None showed any affinity in brain membrane preparations (frontoparietal cortex and hippocampus) or activity in the rat vas deferens bioassay. However, a weak short-lasting contraction was measured with some of these analogs in the rabbit saphenous vein, thus suggesting that the 1-4 and 31-36 segments of the molecule contains pharmacophores recognized by the Y1 receptor subtype. The contribution of the arginine residues also was evaluated in relation with the alpha-helix. Their successive substitution with lysine, an excellent helix-promoter, showed that the replacement of Arg-19 or Arg-25, two residues found in the putative alpha-helix, gave active analogs. Furthermore, the substitution of Arg-19 with lysine increased the activity in the rat vas deferens as well as the affinity in the brain membrane binding assays. On the other hand, the substitution of Arg-33 produced a weak agonist, whereas the replacement of Arg-35 generated an inactive analog in the Y2-pharmacological preparation and a very weak competitor in the CNS binding assays. Interestingly, this latter analog was still active in the rabbit saphenous vein, thus identifying the position 35 as an additional potential target for the development of Y1 versus Y2 specific molecules.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗
PubMed1993

Cytokine indices in Alzheimer's temporal cortex: no changes in mature IL-1 beta or IL-1RA but increases in the associated acute phase proteins IL-6, alpha 2-macroglobulin and C-reactive protein.

Recent immunocytochemical data have demonstrated increases in interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6) and the IL-6-inducible acute phase protein, alpha 2-macroglobulin (alpha 2-M), in Alzheimer's disease (AD) brains. We investigated the levels of these proteins quantitatively using ELISA procedures and determined if increases in IL-1 beta were compensated for by a parallel increase in the endogenous interleukin-1 receptor antagonist (IL-1RA). Comparing control vs. Alzheimer's temporal cortex, we examined mature IL-1 beta, IL-1RA, IL-6, alpha 2-M and C-reactive protein (CRP). The specificities of the ELISA procedures were verified by serial dilutions of the samples; by chromatofocusing, and by Sephadex G-150 gel filtration. There were no differences in the levels of mature IL-1 beta or IL-1RA in AD and control brains. However, IL-6 levels were detectable in 14 of the 16 Alzheimer samples but only 2 of the 14 control samples. There were also significant increases seen in alpha 2-M and CRP levels in the Alzheimer's group compared to controls. These data support previous studies demonstrating a possible up-regulation of neuroimmune function in Alzheimer's cortex; however, we cannot determine, at this time, if this immune reaction is initiated by IL-1 beta.

Acute-Phase Proteins↗
PubMed1993

Localization of sulfated glycoprotein-2/clusterin mRNA in the rat brain by in situ hybridization.

Sulfated glycoprotein-2 (SGP-2) gene expression seems to be constitutively expressed in a variety of tissues and organs, although levels of expression vary widely from one tissue to the other. SGP-2, also known as clusterin, has been reported to be expressed in the central nervous system (CNS). Some possible roles for brain SGP-2 have been postulated. In order to provide a substrate for a better understanding of the functions of this glycoprotein in the CNS, we investigated the detailed anatomical and cellular distribution of SGP-2 mRNA in the adult rat brain as well as the variation in its cellular expression after excitotoxin lesion. Transcripts for SGP-2 were found to be distributed throughout the rat CNS, although regional differences in their prevalence were readily observed. The ependymal lining of the ventricles showed the highest level of expression followed by various gray matter areas, some of which contained very intensively labeled cells. These cells were mostly found among several hypothalamic and brainstem nuclei, the habenular complex, as well as in the ventral horn of the spinal cord, which displayed striking hybridization signals over motoneurons. Occasional cells expressing high levels of SGP-2 transcripts were found in fiber tracts. Highly SGP-2 mRNA-positive resting glial cells were mainly located near the glial limitans and blood vessels. Two areas of relatively low constitutive SGP-2 mRNA expression are shown to produce strong hybridization signals 10 days after the local administration of the excitotoxin kainic acid. This overexpression of SGP-2 transcripts appears to involve GFAP-positive cells. Taken together, these results indicate that in the intact adult rat CNS, various cell populations, including neurons, constitutively express SGP-2 transcripts, whereas in the injured brain, reactive astrocytes become the major producers.

Animals↗
PubMed1993

Effect of guanine nucleotides and temperature on calcitonin gene-related peptide receptor binding sites in brain and peripheral tissues.

Recent data have suggested the existence of at least two major classes of calcitonin gene-related peptide (CGRP) receptors in brain and peripheral tissues [Henke et al., Brain Res., 410 (1987) 404-408; Dennis et al., J. Pharmacol. Exp. Ther., 251 (1989) 718-725; ibid, 254 (1990) 123-128; Quirion et al., Ann. NY Acad. Sci., 657 (1992) 88-105]. However, little is currently known in the structure characteristics of CGRP receptors as cloning as yet to be reported. In the present study, the sensitivity of [125I]humanCGRP alpha binding to guanine nucleotides and temperature was investigated in guinea pig atria (prototypical CGRP1 tissue) guinea pig vas deferens (prototypical CGRP2 tissue) and in the rat brain and cerebellum (mixed assay). Binding isotherms of [125I]hCGRP alpha in those four tissue preparations were curvilinear and best fitted to a two-site model under most assay conditions. The high affinity binding component was highly temperature-sensitive and accounted, under experimental conditions, for up to 18% of the total population of receptors. Moreover, these high affinity sites were also highly sensitive to guanine nucleotides (Gpp(NH)p, 100 microM) in all preparations although to a different extend depending upon assay temperatures. Taken together, this suggests that the different CGRP receptor subtypes present in these tissue all belong to a G-protein coupled receptor family.

Animals↗
PubMed1993

Quantitative autoradiographic localization of [125I]insulin-like growth factor I, [125I]insulin-like growth factor II, and [125I]insulin receptor binding sites in developing and adult rat brain.

Insulin-like growth factors I and II (IGF I and IGF II) and insulin itself, which are structurally related polypeptides, play an important role in regulating brain growth and development as well as in the maintenance of its normal functions during adulthood. In order to provide a substrate for the better understanding of the roles of these growth factors, we have investigated the anatomical distribution as well as the variation in the density of [125I]IGF I, [125I]IGF II, and [125I]insulin receptor binding sites in developing and adult rat brain by in vitro quantitative autoradiography. The distributional profile of [125I]IGF I, [125I]IGF II, and [125I]insulin receptor binding sites showed a widespread but selective regional localization throughout the brain at all stages of development. The neuroanatomic regions which exhibited relatively high density of binding sites with each of these radioligands include the olfactory bulb, cortex, hippocampus, choroid plexus, and cerebellum. However, in any given region, receptor binding sites for IGF I, IGF II, or insulin are concentrated in anatomically distinct areas. In the cerebellum, for example, [125I]IGF II receptor binding sites are concentrated in the granular cell layer, [125I]insulin binding sites are localized primarily in the molecular layer, whereas [125I]IGF I receptor binding sites are noted in relatively high amounts in granular as well as molecular cell layers. The apparent density of sites recognized by each radioligand also undergoes remarkable variation in most brain nuclei, being relatively high either during late embryonic (i.e., IGF I and IGF II) or early postnatal (i.e., insulin) stages and then declining gradually to adult levels around the third week of postnatal development. These results, taken together, suggest that each receptor-ligand system is regulated differently during development and thus may have different roles in the process of cellular growth, differentiation, and maintenance of the nervous system. Furthermore, the localization of [125I]IGF I, [125I]IGF II, and [125I]insulin receptor binding sites over a wide variety of physiologically distinct brain regions suggests possible involvement of these growth factors in a variety of functions associated with specific neuronal pathways.

Aging↗
PubMed1993

Evaluation of truncated neuropeptide Y analogues with modifications of the tyrosine residue in position 1 on Y1, Y2 and Y3 receptor sub-types.

Substitutions of the tyrosine residue in position 1 of truncated neuropeptide Y (N-terminal fragment 1-4 linked to C-terminal fragment 18-36 by the epsilon-aminocaproic acid) produced analogues that compete for specific [125I]polypeptide YY (PYY) binding in the frontoparietal cortex (Y1-enriched) with a profile best fitted to a two site-model with KD values in the low and high nM range, respectively. In the hippocampal membrane preparations (Y2-enriched), halogen substitutions on the aromatic ring generated analogues with competition profiles best fitted to a one-site model, revealing differences between the two binding assays and the interaction of these analogues with the Y1 and Y2 receptor sub-types. In the rat vas deferens (Y2-enriched), all truncated analogues inhibited the twitch response with similar or slightly weaker potency than the native molecule. In contrast, these molecules were markedly less potent than neuropeptide Y (NPY) in the rabbit saphenous vein (Y1-enriched) and the rat distal colon (Y3-enriched). Some of the truncated analogues were inactive at up to microM concentrations in the rat distal colon, demonstrating the distinct structural requirement of the receptor sub-type present in this bioassay. These results revealed that amino acid residues between positions 5 and 17 are critical for the maintenance of optimal affinity for the NPY receptors present in the rabbit saphenous vein and the rat distal colon.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

NGF level of is not decreased in the serum, brain-spinal fluid, hippocampus, or parietal cortex of individuals with Alzheimer's disease.

Although the cause of Alzheimer's disease (AD) is unknown, nerve growth factor (NGF) has gained attention as a therapeutic agent for the disease. Because NGF maintains the magnocellular cholinergic neurons that are damaged in AD, research interests have been focused on the change in NGF level in patients with AD. This is the first reported study in which human NGF levels were accurately measured and compared between normal and AD samples. We measured NGF levels using enzyme immunoassay (EIA) system for human NGF and found no difference in NGF level in serum, brain-spinal fluid, or brain (hippocampus and parietal cortex) obtained from normal people and patients with AD. These results suggest that a decrease in the NGF level is not a causative factor of AD.

Alzheimer Disease↗
PubMed1993

Brain calcium channel related dihydropyridine and phenylalkylamine binding sites in Alzheimer's, Parkinson's and Huntington's diseases.

Disruptions of normal calcium (Ca2+) homeostasis in human aging processes, are well documented. The existence of at least four distinct types of Ca2+ channels, L-, T-, P-, and N-, have been reported in the central nervous system. Binding sites for clinically useful dihydropyridines (DHP) and phenylalkylamines (PA) are located on the L-type Ca2+ channels. In the present study, DHP/[3H]PN200-110 and PA/[3H](-)-D-888 binding parameters were determined in various brain areas obtained at autopsy from Alzheimer's (AD), Parkinson's (PD), Huntington's (HD) disease patients, and healthy age-matched controls as a means to assess the integrity of L-type channels in these neurological disorders often associated with the aging brain. DHP and PA receptor binding parameters (KD and Bmax) were not significantly altered in any of the brain regions studied in AD and PD. However, a significant decrease in the maximal binding capacity of [3H]PN200-110 was observed in the striatum of HD patients. Taken together, this suggests that DHP and PA binding sites associated to L-type Ca2+ channels are mostly preserved in AD and PD brains. Accordingly, the use of DHP- and/or PA-related drugs in these neurological disorders should not be hindered by deficits in their related Ca2+ channel binding proteins.

Aged↗
PubMed1993

[3H]phorbol ester binding sites and neuronal plasticity in the hippocampus following entorhinal cortex lesions.

Entorhinal cortex lesioning (ECL) produces a loss of more than 80% of the synapses in the outer molecular layer of the hippocampus. However, the loss of synapses is transient. Beginning a few days after denervation, new synapses are formed, virtually replacing the lost inputs within 2 months. Synaptic remodelling induced by ECL is associated with specific modifications of neurotransmitters, hormones and growth factors. Particularly, protein kinase C (PKC) plays important functional roles in receptor-mediated transmembrane signal transduction. PKC is also involved in various aspects of synaptic plasticity, such as cellular growth and differentiation. To investigate further the potential roles of PKC in synaptic plasticity observed in the ECL model, [3H]phorbol 12,13-dibutyrate ([3H]PDBu) binding, a putative marker of PKC, was examined at different times post-lesion. [3H]PDBu binding sites transiently decreased bilaterally at 2 and 8 days post-lesion (20%) in different laminae and sub-fields of the rostral hippocampus but returned to control values at 14 and 30 days post-lesion. In caudal portion of the hippocampus, [3H]PDBu binding was also decreased at 2 days post-lesion but only on the contralateral side. Interestingly, [3H]PDBu binding sites in the cortex increased by up to 30% in the contralateral side while no significant change was observed in the ipsilateral side at any time post-lesion. It is known that PKC can be regulated by different systems following alterations of neuronal and glial activity. We suggest that these could be involved in the response of PKC and [3H]PDBu binding sites following ECL. Moreover, PKC seemed to be modified in different brain areas in neuronal inputs from the entorhinal cortex and the subsequent reinnervation process.

Acetylcholinesterase↗