bluuebunny/crossref_metadata_2025_split huggingface dataset:
Age‐related remodeling of glutamic‐acid decarboxylase‐labeled elements in deafferented piriform cortex of rats
Authors: Nousek‐Goebl N. A. , Westrum L. E. , Wu J. ‐Y. 
Published: December 2004

AbstractOlfactory bulb (OB) removal has been shown to result in plasticity in the piriform cortex (PC) that is age dependent. We are studying this phenomenon using immunoelectron microscopy of glutamic acid decarboxylase immunoreactivity (GAD, the enzymatic precursor for GABA) at selected postnatal ages and in adults with emphasis on short survival times of 4–7 days after OB ablation. Normally GAD‐labeled synaptic terminals form type II symmetric contacts from unlabeled dendrites and GAD‐labeled dendrites receive type I, asymmetric contacts from unlabeled terminals (Westenbroek, el al., 1988a). The OB lesion results in degenerating terminals with type I contacts onto unlabeled and onto GAD‐labeled dendrites. Type I postsynaptic sites may be seen partially contacted by or entirely devoid of degenerating terminals and occasionally may be apposed to variable degrees by normal unlabeled or by GAD‐positive terminals. Subsequently, some GAD‐labeled terminals may form asymmetric type I contacts usually with unlabeled dendrites and rarely with GAD‐labeled dendrites. The findings are most common in the youngest subjects and essentially absent in the adult subjects. A sequence of reinnervation of deafferented type I sites by GAD‐labeled terminals is suggested for the formation of this “atypical” synapse and the sequelae of this reorganization are discussed.
Olfactory deprivation increases dopamine D2 receptor density in the rat olfactory bulb
Authors: Guthrie K. M. , Pullara J. M. , Marshall J. F. , Leon M. 
Published: December 2004

AbstractUnilateral olfactory deprivation during postnatal development results in significant anatomical and neurochemical changes in the deprived olfactory bulb. Perhaps the most dramatic neurochemical change is the loss of dopaminergic expression by neurons of the glomerular region. We describe here the effects of early olfactory deprivation on other elements of the bulb dopaminergic system, namely the dopamine receptors of the olfactory bulb. Rat pups had a single naris occluded on postnatal day 2 (PN2). On PN20 or PN60, animals were sacrificed and the bulbs were examined for catecholamine levels or D2 and D1 dopamine receptor binding. Receptor densities were quantified by in vitro autoradiography using the tritiated antagonists spiperone (D2) and SCH23390 (D1). Dopamine uptake sites were similarly examined using tritiated mazindol. No significant specific labeling of D1 or mazindol sites was observed in the olfactory bulbs of control or experimental animals at either age. Normal animals displayed prominent labeling of D2 sites in the glomerular and nerve layers. After 60 days of deprivation, deprived bulbs exhibited an average increase in D2 receptor density of 32%. As determined by Scatchard analysis, the mean values for Kd and Bmax were 0.134 nM and 293 fmol/mg protein in normal bulbs, and 0.136 nM and 403 fmol/mg protein in deprived bulbs. The results suggest that, as in the neostriatum, dopamine depletion in the olfactory bulb leads to an upregulation of D2 receptor sites. This change may represent an attempt by the system to adapt neurochemically to reduced dopaminergic activity and thereby maintain bulb function.
Interaction of β‐funaltrexamine with [3H]cycloFOXY binding in rat brain: Further evidence that β‐FNA alkylates the opioid receptor complex
Authors: Rothman Richard B. , Bykov Victor , Mahboubi Artin , Long Joseph B. , Jiang Qi , Porreca Frank , de Costa Brain R. , Jacobson Arthus E. , Rice Kenner C. , Holaday John W. 
Published: December 2004

Abstractβ‐Funaltrexamine (β‐FNA) is an alkylating derivative of naltrexone. In addition to acting as an irreversible inhibitor of μ‐receptor‐mediated physiological effects, intracerebroventricular (i.c.v.) administration of β‐FNA to rat attenuates the ability of selective δ receptor antagonists and naloxne to reverse δ receptor‐mediated effects. Moreover, recent work demonstrated that i.c.v. administration of β‐FNA alters the conformation of the opioid receptor complex, as inferred by a decrease in the Bmax of the lower affinity [3H][D‐ala2, D‐leu5]enkephalin binding site. Consistent with the decreased potency of naloxone as an inhibitor of δ receptor mediated effects, β‐FNA doubled the naloxone IC50 for displacing [3H][D‐ala2, D‐leu5]enkephalin from its lower affinity binding site. These data collectively support the hypothesis that the opioid receptor complex postulated to mediate μ‐δ interactions in vivo is identical to the opioid receptor complex as defined by vitro ligand binding studies. A direct prediction of this hypothesis is that β‐FNA should increase the Kd of antagonists for the μ binding site (μcx) of the receptor complex. The data reported in this paper demonstrate that β‐FNA doubled the IC50 of the potent narcotic antagonist, 6‐desoxy‐6β‐fluoronaltrexone (cycloFOXY) for displacing [3H][D‐ala2, D‐leu5]enkephalin from its lower affinity binding site, and doubled the Kd of [3H]cycloFOXY for its μ binding site, providing additional data that the μ binding site labeled by [3H]cycloFOXY is the μ binding site of the opioid receptor complex. β‐FNA also altered the K binding site labeled by [3H]cycloFOXY, and when administered intrathecally to mice, β‐FNA produced a longlasting antinociception in the acetic acid writhing test.
Organization of mitochondria in olfactory bulb granule cell dendritic spines
Authors: Cameron Heather A. , Kaliszewski Christine K. , Greer Charles A. 
Published: December 2004

AbstractIn contrast to dendritic spines with only postsynaptic functions, the spines of olfactory bulb granule cells subserve both pre‐and postsynatic roles. In single sections these spines were previously seen to contain mitochondria, most likely needed to provide energy for presynaptic functions, but their frequency and distribution were unkown. In order to understand the organization of mitochondria in these specialized dendritic appendages, we have studied the geometry and cytoplasmic organization of granule cell spines with computer‐assisted reconstructions of serial electron micrographs. The spine heads were seen to be elliptical in shape with a single pair of reciprocal synapses on the concave face apposed to the mitral/tufted cell dendrite. Mitochondria were found localized in the spine neck as well as the spine head and often extended between the two compartments, Based or their variable distribution it seems reasonable to suggest that these mitochondria are motile and move in and out of spine compartments from the parent dendrite. Spine apparatus was apparent in most of the spines as membrane bound cisterns of smooth endoplasmic reticulum located close to mitochondria. The possible role of spine apparatus in facilitating the movement of mitochondira in the necks and heads of granule cell spines in the absence of microtubules is discussed.
Comparison of the effects of various typical and atypical antipsychotic drugs on the suppressant action of 2‐methylserotonin on medial prefrontal cortical cells in the rat
Authors: Ashby Charles R. , Minabe Yoshio , Edwards Emmeline , Wang Rex Y. 
Published: December 2004

AbstractIn this study, we report the effects of various typical and atypical antipsychotic drugs (APDs) on the suppressant action of microiontophoretically applied 2‐methylserotonin (2‐Me‐5HT, a 5‐HT3agonist) on medial prefrontal cortical (mPFc) cells. The microiontophoresis of 2‐Me‐5HT (10–80 nA) produced a current‐dependent suppression of mPFc cells' firing, and this effect was blocked by various 5‐HT3 antagonists. The microiontophoresis of the atypical APDs clozapine and a structurally related compound, RMI 81, 582, mimicked the action of the 5‐HT3 antagonists. In addition, the intravenous administration of clozapine and RMI 81, 582 antagonized the suppressant action produced by the iontophoretic application of 2‐Me‐5HT on mPFc cells. However, the suppressant action of 2‐Me‐5HT was not blocked by the typical APDs haloperidol and chlorpromazine. The putative atypical APDs risperidone, setoperone, CL 77328, SCH 23390, CGS 10746B, 1‐sulpiride, and thioridazine were ineffective in antagonizing 2‐Me‐5HT's action. Overall, our results suggest that the majority of putative atypical APDs do not interact with 5‐HT3 binding sites in the brain. Whether the interaction of clozapine and RMI 81, 582 with 5‐HT3 sites is correlated with their therapeutic efficacy or lower potential to induce neurological side effects remains to be determined.
Ultrastructure of aberrant serotonin‐immunoreactive fibers in the caudate putamen complex of the aged rat
Authors: van Luijtelaar Mariëlle G. P. A. , Wouterlood Floris G. , Tonnaer Jeroen A. D. M. , Steinbusch Harry W. M. 
Published: December 2004

AbstractDegeneration of neurons in the central nervous system is associated with morphological changes. Previous observations made at the light microscopical level indicated degeneration of serotonin‐immunoreactive (IR) fibers in the aged rat brain. In this study, a comparison at the ultrastructural level was made between serotonin‐IR normal thin and aberrant swollen varicose fibers in the caudate‐putamen complex of the aged rat. Ultrastructural features such as the size and content of the thin varicose fibers resembled those in the caudate‐putamen complex of the young rat as reported by others. The aberrant profiles were swollen, reaching a size of 6 μm. Their vesicles varied in size and were no longer uniformly round. Moreover, distorted mitochondria and membranefilled vacuolelike structures were a common feature of the aberrant profiles. These changes are indicative of a degenerative process and give further evidence that, whereas many serotonergic fibers are preserved at high age, other serotonergic fibers are degenerating in the caudate‐putamen complex of the aged rat.
Characterization and distribution of [3H]ohmefentanyl binding sites in the human brain
Authors: Wang Hong , Sarrieau Alain , Pélaprat Didier , Roques Bernard P. , Vanhove Alain , Kopp Nicolas , Chi Zhi‐Qiang , Rosténe William 
Published: December 2004

AbstractBinding properties and localization of [3H]ohmefentanyl, a new ligand for μ opioid receptors, were investigated on normal human brain sections. Binding assays performed at the level of the basal ganglia revealed: (1) a steady‐state binding reached after 60 min incubation at room temperature, (2) the presence, in saturation experiments, of an apparent single class of binding sites with a Kd = 1.68 ± 0.45 nM and a Bmax = 162 ± 9 fmol/mg protein, (3) an order of potency to inhibit [3H]ohmefentanyl binding as follows: ohmefentanyl > [D‐Ala2, MePhe4, Gly‐ol5]enkephalin (DAGO) > ethylketocyclazocine (EKC) ≫ Tyr‐D‐Ser(OtBu)‐Gly‐Phe‐Leu‐Thr(OtBu) (BUBU) and U‐50, 488H. Quantitative autoradiography showed an heterogeneous distribution of [3H]ohmefentanyl binding sites with the highest densities in amygdala, medial geniculate body, thalamus, and caudate nucleus. Binding characteristics and anatomical distribution also show that [3H]ohmefentanyl may bind to a small proportion of additional sites called “DAGO‐inaccessible [3H]ohmefentanyl specific binding sites.” [3H]Ohmefentanyl binding to these sites can be partly inhibited by s̀ ligands such as 1, 3‐di‐o‐tolyguanidine (DTG) and haloperidol. However, unlabeled DAGO inhibited more than 80% of [3H]ohmefentanyl specific binding in most of the human brain regions studied, suggesting that the major population of sites labeled by [3H]ohmefentanyl represented μ opioid receptors.
Clinical and biochemical aspects of depressive disorders: I. Introduction, classification, and research techniques
Authors: Caldecott‐Hazard Sally , Guze Barry H. , Kling Mitchel A. , Kling Arthur , Baxter Lewis R. 
Published: December 2004

AbstractThe present review focuses on recent data from clinical and animal research concerning the biochemical bases of depressive disorders, diagnosis, and treatment. In addition to integrating these data, problems and future directions in this research are discussed. The review is presented in three parts. This study, Part I, describes diagnostic classification schemes for depressive disorders, some epidemiological and biological correlates of the classifications, and research techniques for investigating depressive disorders. Research techniques include animal models, human biochemical techniques, and Postron Emission Tomography. In a future issue, Part II will discuss various transmitter/receptor theories of depressive disorders, e.g., noradrenergic, serotonergic, cholinergic, and dopaminergic, GABAergic, and peptidergic theories. Also in a future issue, Part III will discuss treatments for depression and some of the controversies in the field.
Influence of age on N‐methyl‐D‐aspartate antagonist binding sites in the rat brain studied by in vitro autoradiography
Authors: Miyoshi Rie , Kito Shozo , Doudou Naomi , Nomoto Teruko 
Published: December 2004

AbstractThe N‐methyl‐D‐aspartate (NMDA) receptor complex has been considered to consist of an L‐glutamate recognition site, a strychine‐insensitive glycine modulatory site, and a voltage‐dependent cation channel. In this study, an effect of age on NMDA antagonist binding sites was investigated through quantitative in vitro autoradiography with 3H‐3‐((+)‐2‐carboxypiperazin‐4‐yl)propyl‐1‐phosphonic acid (CPP). 3H‐CPP binding sites were most concentrated in the hippocampus and cerebral cortex where NMDA receptors have been demonstrated to be involved in synaptic transmission. In aged rats, 3H‐CPP binding sites in the hippocampus and cerebral cortex were not significantly changed. As for other brain regions, there was an age‐dependent decline of binding sites only in the caudate‐putamen and nucleus accumbens. Our previous study revealed that strychine‐insensitive glycine receptors were markedly reduced in telencephalic regions in the aged rat brain. Taking these findings into consideration, is concluded that glycine receptors but not NMDA antagonist binding sites are severely altered in telencephalic regions of aged animals. It is considered that within the NMDA receptor complex, glycine receptors may be selectively affected in the aging process.
Neuroanatomic specificity and time course of alterations in rat brain serotonergic pathways induced by MDMA (3,4‐methylenedioxymethamphetamine): Assessment using quantitative autoradiography
Authors: Battaglia George , Sharkey John , Kuhar Michael J. , de Souza Errol B. 
Published: December 2004

AbstractThe Widely abused “designer” durg MDMA (3,4‐methylenedioxymethamphetamine) has been shown to caused marked and long‐lasting changes in brain serotonergic systems. The present study uses quantitative in vitro autoradiography of 3H‐paroxetine labeled 5‐HT uptake sites to assess the time‐dependent effects of MDMA on 5‐HT neurons in specific neuroanatomic loci. Following treatment with MDMA (20 mg/kg, b.i.d. for 4 days), marked decreases in 5‐HT uptake sites were observed in a number of brain regions known to receive projections of ‐5HT neurons. These regions included cerebral cortex, caudate nucleus, hippocampus, nucleus accumbens, olfactory tubercle, superior and inferior colliculi, geniculate nuclei, and most thalamic nuclei. In contrast, other areas such as the septal nuclei and some thalamic nuclei which also receive 5‐HT projections were not substantially affected by this drug. In most regions, decreases in 5‐HT uptake sites occurred within 24 hours of the last dose of MDMA and persisted at the 2 week time point. Some regions such as dorsal striatum exhibited a time‐dependent reduction with greater reductions occurring at 2 weeks rather than immediately following the MDMA treatment regimen. The density of 5‐HT uptake sites in other regions such as endopiriform nucleus and substantia nigra at the 2 week versus 18 hour time point indicated some degree of region‐specific recovery. Regions which demonstrated no significant reduction in 5‐HT uptake sites included the dorsal and median raphe nuclei, ventral tegmental area, central grey, interpeduncluar nucleus, locus coerulus, pontine reticular formation and cerebellum. Likewise, region containing 5‐HT axons of passage (e.g., indusium griseum and lateral hypothalamus) appeared to be insensitive to the neurotoxic effects of MDMA on 5‐HT neurons. Furthermore, the neurotoxic effects of MDMA showed specificity in that the catecholamine neurons labeled by 3H‐mazindol were unaffected by the treatment regimen. These data indicate that the preferential degeneration of serotonergic neurons by MDMA is mediated primarily at 5‐HT terminal regions, whereas regions containg 5‐HT perikarya and axons of passage remain relatively unaffected. In addition, the observed time‐dependent reductions and recovery of 5‐HT uptake sites which were detected within 2 weeks of the treatment regimen in certain brain regions suggest region‐specific differences in recovery of 5‐HT systems from MDMA‐induced lesion.
Calcitonin gene‐related peptide in the amygdaloid complex of the rat: Immunohistochemical and quantitative distribution, and drug effects on calcium dependent, potassium‐evoked in vitro release
Authors: Haring C. , Humpel C. , Skofitsch G. , Krobath J. , Javorsky F. , Saria A. 
Published: December 2004

AbstractThe amygdaloid complex is an area with a high concentration of calcitonin gene‐related peptide. In the present paper, immunohistochemical studies revealed a dense innervation of the central nucleus originating most probably from the bed nuclei of the stria terminalis. For determination of tissue concentrations of calcitonin gene‐related peptidelike immunoreactivity, the amygdaloid complex was dissected into four parts. The distribution was found to be uneven with the highest concentration (1153.3 fmol/mg protein) in the portion including the nucleus amygdaloideus centralis. High performance liquid chromatographic analysis from an extract of amygdaloid tissue showed that 97% of the calcitonin gene‐related peptidelike immunoreactivity measured by radioimmunoassay is authentic rat calcitonin gene%related peptide alpha or beta. Release of calcitonin gene‐related peptidelike immunoreactivity was measured in superfused slices of amygdalae pooled from three rats. High potassium (60 mM) caused a significant release of calcitonin gene‐related peptidelike immunoreactivity (from 0.88% of total tissue content to 1.91%) from the amygdaloid complex in vitro, which was blocked in calcium‐free buffer. Pretreatment with haloperidol or clozapine caused a significant reduction of the 60 mM potassium‐evoked release, compared with a saline treated control group (control 21.0 fmol; haloperidol 2.8 fmol; clozapine 8.8 fmol) and an increase of tissue levels after haloperidol treatment by 43%. These results demonstrate that calcitonin gene‐related peptide is integrated in amygdaloid functions and possibly a target for actions of neuroleptic drugs.
Beta‐adrenergic receptor subtypes in the basal ganglia of patients with Huntington's chorea and Parkinson's disease
Authors: Waeber Christian , Rigo Monique , Chinaglia Giorgia , Probst Alphonse , Palacios José M. 
Published: December 2004

AbstractThe density of [125I]iodo‐cyanopindolol binding to beta‐1 and beta‐2 adrenergic receptors was studied in post mortem basal ganglia samples of Huntington's chorea and Parkinson's disease patients using autoradiography. Whereas no significant changes were observed in sections from Parkinson's and Huntington's chorea grade 2 patients, a nearly complete loss of beta‐1 binding sites was observed in the basal ganglia of Huntington patients at later stages of the disease. The concentration of beta‐2 receptors was increased by a factor 2 in the posterior putamen of all choreic cases. These results are consistent with the view that beta‐1 receptors are predominantly located on a subpopulation of neurons which degenerate at late stages of Huntington's chorea, while beta‐2 receptors are present mainly on glial elements.
The effect of the acetylcholine transport blocker vesamicol on central cholinergic pressor neurons
Authors: Buccafusco Jerry J. , Wei Jian , Kraft Katherine L. 
Published: December 2004

AbstractVesamicol (AH 5183) inhibits the uptake of acetylcholine into cholinergic neuronal storage vesicles. Earlier in vitro studies have demonstrated that such inhibition can lead to a failure of transmission, particularly in peripheral cholinergic tissues. The present study was designed to determine whether vesamicol could inhibit central cholinergic transmission in conscious freely moving rats. Central (lateral cerebroventricular) injection of 20 μg of vesamicol significantly reduced the hypertensive and bradycardic response to subsequent central injection of physostigmine in spontaneously hypertensive rats. Inhibition of the pressor response was greatest when physostigmine was administered 1 hr after vesamicol. Acetylcholine and choline levels were determined in three brain regions derived from rats treated one hr earlier with either vehicle or vesamicol. Acetylcholine levels were found to be unaltered after vesamicol treatment, although choline levels were significantly higher in two brain regions. These results are consistent with the ability of vesamicol to inhibit the function of central cholinergic cardiovascular regulatory neurons. The mechanism for this inhibition is not related to depletion of total brain acetylcholine content but may be due to depletion of a small critical pool of transmitter.
Actions of phosphomonoesters on CA1 hippocampal neurons as revealed by a combined electrophysiological and nuclear magnetic resonance study
Authors: Bradler James E. , Barrionuevo German , Panchalingam Kanagasabi , McKeag Dennis , Pettegrew Jay W. 
Published: December 2004

AbstractPhosphomonoesters (PMEs), precursors of membrane phospholipids, are found in high levels in the developing brain and in Alzheimer's disease brain. The present study details the neurophysiological and metabolic effects of acute PME elevation on the Fisher 344 rat in vitro hippocampal slice. Two abundant PMEs, phosphoethanolamine (PE) and L‐phosphoserine (PS), reliably altered properties of synaptic transmission at the Schaffer collateral/commissural—CA1 cell synapse. Specifically, PE reversibly depressed the amplitude of population EPSPs at millimolar concentrations but had no effect at micromolar concentrations. PS had biphasic effects on population EPSPs, inducing first a reduction followed by an enhancement of response amplitude. In contrast to PE, the effects of PS were not reversible; population EPSPs were augmented during the wash of PS, and the CA3 region generated evoked (but not spontaneous) epileptiform discharges. 31P nuclear magnetic resonance spectroscopy revealed enhanced slice uptake of PS compared to PE. There was no significant effect of PE on slice high‐energy phosphates but incubation with PS significantly lowered slice phosphocreatine (PCr) and ATP concentrations. These observations indicate that the slice uptake of PS could be energy requiring and the enhanced response amplitude observed at 5 mM PS also could produce a drain on high‐energy phosphates. Possible modes of PME action on hippocampal physiology are discussed.