PubMed Health⌕ Search

Biomedical subjects

R L Albin

Publications and source records attributed to R L Albin.

At least 19 recordsLinked to original sources
PubMed1998

Localization of mGluR1a-like immunoreactivity and mGluR5-like immunoreactivity in identified populations of striatal neurons.

Metabotropic glutamate receptors are important mediators of excitatory amino acid neurotransmission in the striatum. Two-color immunofluorescence histochemistry and immunohistochemistry in combination with retrograde tract-tracing techniques were used to examine the distribution of metabotropic glutamate receptor subtypes 1a and 5 (mGluR1a and mGluR5) among identified subpopulations of striatal projection neurons and interneurons. The majority of striatopallidal and striatonigral neurons were double-labeled for both mGluR1a or mGluR5. Approximately 60% to 70% of either striatonigral or striatopallidal neurons expressed mGluR1a- or mGluR5-like immunoreactivity. The percentage of double-labeled striatopallidal or striatonigral projection neurons did not differ among striatal quadrants. Striatal interneurons expressing parvalbumin or somatostatin or choline acetyltransferase exhibited varying degrees of expression of mGluR1a or mGluR5. Virtually all (94%) parvalbumin-immunoreactive striatal neurons expressed mGluR1a-like immunoreactivity with a majority (79%) of these neurons expressing mGluR5-like immunoreactivity. A high percentage (89%) of striatal choline acetyltransferase-immunoreactive neurons were double-labeled for mGluR1a-like immunoreactivity. Approximately 65% of striatal choline acetyltransferase-immunoreactive neurons expressed mGluR5-like immunoreactivity. A majority (65%) of somatostatin-immunoreactive striatal interneurons expressed mGluR1a-like immunoreactivity with a slightly lower percentage (55%) expressing mGluR5-like immunoreactivity. These findings indicate considerable heterogeneity among striatal projection and interneurons with respect to mGluR1a and mGluR5 expression. There may be subpopulations of striatonigral and striatopallidal projection neurons. These results are consistent as well with prior data indicating subpopulations of the different classes of striatal interneurons.

Animals↗
PubMed1998

Chronic administration of quinolinic acid in the rat striatum causes spatial learning deficits in a radial arm water maze task.

Chronic intrastriatal administration of quinolinic acid (QA) in the rat produces a pattern of neurodegeneration similar to that seen in Huntington's disease (HD). Although these changes have been related to transient motor abnormalities, the effects of chronic QA administration on cognitive abilities have not been assessed. The present study investigated whether the striatal deterioration observed during chronic QA administration produces cognitive impairments in this animal model of HD by testing the effects of chronic administration of QA on spatial learning ability of rats in a radial arm water maze (RAWM) task. Rats were given bilateral implantation of a chronic dialysis probe apparatus which delivered either vehicle or QA (20 mM) into the striatum. Beginning 1 day after implantation, the rats were tested daily for 3 weeks in the RAWM. Nocturnal activity levels were also assessed at 1-, 3-, 5-, 7-, 14-, and 21-days following probe implantation. Results of behavioral testing indicated that chronic exposure to QA causes spatial learning deficits in the RAWM task with only a transient increase in activity levels. Collectively, these results suggest that chronic striatal exposure to QA mimics some aspects of the cognitive deficits observed in HD.

Animals↗
PubMed1998

Fuch's corneal dystrophy in a patient with mitochondrial DNA mutations.

A patient with Fuch's corneal dystrophy, sensorineural hearing loss, diabetes, cardiac conduction defects, ataxia, and hyperreflexia is described. Analysis of lymphocyte mitochondrial DNA showed missense mutations usually associated with Leber's hereditary optic neuropathy. The occurrence of Fuch's dystrophy in this patient and the biology of corneal endothelial cells suggest that mitochondrial defects could be the cause of Fuch's endothelial dystrophy.

DNA, Mitochondrial↗
PubMed1997

Ectopically expressed CAG repeats cause intranuclear inclusions and a progressive late onset neurological phenotype in the mouse.

The mutations responsible for several human neurodegenerative disorders are expansions of translated CAG repeats beyond a normal size range. To address the role of repeat context, we have introduced a 146-unit CAG repeat into the mouse hypoxanthine phosphoribosyltransferase gene (Hprt). Mutant mice express a form of the HPRT protein that contains a long polyglutamine repeat. These mice develop a phenotype similar to the human translated CAG repeat disorders. Repeat containing mice show a late onset neurological phenotype that progresses to premature death. Neuronal intranuclear inclusions are present in affected mice. Our results show that CAG repeats do not need to be located within one of the classic repeat disorder genes to have a neurotoxic effect.

Animals↗
PubMed1997

Metabotropic glutamate agonist-induced rotation: a pharmacological, FOS immunohistochemical, and [14C]-2-deoxyglucose autoradiographic study.

Metabotropic glutamate receptors (mGluRs) are a major class of excitatory amino acid receptors. Eight mGluR subtypes, coupled to a variety of effector systems, have been cloned. These receptors have been classified into three groups based on amino acid sequence homology, effector systems, and pharmacological profile. Group I mGluRs increase phosphoinositide turnover, whereas groups II and III mGluRs are negatively coupled to adenylyl cyclase. The striatum possesses a high density of mGluR binding sites, and several mGluR mRNAs and proteins are expressed by striatal neurons. In rats, unilateral striatal injection of the nonsubtype selective mGluR agonist 1-aminocyclopentane-1S,3R-dicarboxylic acid (1S,3R-ACPD) results in contralateral rotation with delayed onset, thought to be secondary to an increase in dopamine release. We sought to determine the mGluR subtype(s) involved, the modulation of the rotation by other basal ganglia neurotransmitter systems, and the functional anatomy underlying the rotational behavior. The group I mGluR agonist 3,5-dihydroxyphenylglycine (DHPG) induced contralateral rotation in a dose-dependent manner, whereas group II and group III agonists were ineffective. Rotation induced by DHPG or 1S,3R-ACPD was attenuated by group I antagonists, but not by group II or group III antagonists. This suggests that the rotation is mediated by group I mGluRs. Rotation induced by DHPG or 1S,3R-ACPD was attenuated by pretreatment with antagonists at muscarinic cholinergic, adenosine A2, dopamine D2, or dopamine D1 receptors. Examination of FOS-like immunoreactivity after group I and group II mGluR agonist administration suggests increased activity in the striatopallidal pathway. However, [14C]-2-deoxyglucose uptake studies indicate increased activity in nuclei of the striatopallidal (indirect) pathway, particularly in the subthalamic nucleus, only after group I mGluR activation.

Animals↗
PubMed1997

Paroxysmal dystonic choreoathetosis linked to chromosome 2q: clinical analysis and proposed pathophysiology.

We describe clinical features of a large Polish-American kindred in which autosomal-dominant, paroxysmal dystonic choreoathetosis (PDC) was linked to a locus on chromosome 2q. Episodes of generalized dystonia and choreoathetosis involving the face and all extremities began in early childhood, lasted for 30 minutes to several hours, and occurred up to several times each week. There was no interruption of consciousness and EEGs were normal during the episodes. Paroxysmal dyskinesia occurred at rest both spontaneously and following caffeine or alcohol consumption. Neurologic examinations were normal between attacks. The cause of PDC is unknown. We deduced a model of PDC pathophysiology from analyzing neurophysiologic effects of alcohol and caffeine (which provoke attacks of PDC), the variably beneficial effects of levodopa-carbidopa, and the occurrence of dystonia and paroxysmal dyskinesia in biopterin synthesis disorders. We propose that nigrostriatal neurons in PDC patients have either marginally deficient dopamine synthesis or excessive alcohol- and caffeine-induced dopamine release; and that following alcohol- and caffeine-induced dopamine release, PDC patients experience a period of dopamine deficiency.

Athetosis↗
PubMed1997

Cerebral metabolic differences in Parkinson's and Alzheimer's diseases matched for dementia severity.

UNLABELLED: Despite controversial clinicopathological distinctions between Parkinson's disease with dementia (PDD) and Alzheimer's disease (AD), similar patterns of metabolic reduction in the posterior brain were reported previously using PET with [18F]fluorodeoxyglucose. The current study was designed to examine more specific regional differences in cerebral glucose metabolism between PDD and AD using accurate and objective brain mapping techniques. METHODS: This study included nine normal subjects, nine PDD patients and nine AD patients. PDD and AD groups were matched carefully for age, sex and general dementia severity as measured by Mini-Mental State Examination and Clinical Dementia Rating scales. Each subject underwent [18F]fluorodeoxyglucose-PET and neuropsychological testing. After anatomic standardization of PET image sets and stereotactic data extraction, absolute and normalized cerebral metabolic rates were assessed by region of interest and pixel-by-pixel analyses. RESULTS: PDD and AD showed global glucose metabolic reduction with similar regional accentuation involving the lateral parietal, lateral temporal and lateral frontal association cortices and posterior cingulate cortex in comparison to normal controls. When comparing between PDD and AD, however, PDD showed greater metabolic reduction in the visual cortex and relatively preserved metabolism in the medial temporal cortex. CONCLUSION: Although a common feature of metabolic abnormalities in the posterior brain exists in PDD and AD, the presence of regional metabolic differences suggests different degrees and combinations of disease specific underlying pathological and neurochemical processes.

Aged↗
PubMed1996

Synergistic effects of chronic exposure to subthreshold concentrations of quinolinic acid and malonate in the rat striatum.

Adult rats received chronic intrastriatal dialytic exposure to quinolinic acid (QUIN), malonate, or a combination of QUIN and malonate. The combination of subthreshold concentrations of QUIN (4 mM) and malonate (400 mM) produced lesions larger than did either QUIN or malonate alone. The neurotoxic effect of QUIN combined with malonate was subsequently blocked by co-administration of the NMDA receptor antagonist MK-801 (1 mM). These findings indicate that malonate synergistically enhances NMDA receptor mediated excitotoxicity.

Animals↗
PubMed1996

Intraseptal administration of (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid induces immediate early gene expression in lateral septal neurons.

Prior work has shown that activation of metabotropic glutamate receptors can induce burst firing and a form of NMDA receptor independent long term potentiation in lateral septal slice preparations. To study this phenomenon in vivo we used the expression of immediate early gene products as markers for increased neuronal activity following intraseptal injection of the metabotropic agonist 1S,3R-ACPD. Intraseptal injection of 1S,3R-ACPD induced the expression of Fos-like, Jun B-like and Krox24-like immunoreactivity in lateral septal neurons in a dose-dependent fashion. Immediate early gene product expression peaked at 4 to 6 h post-injection and then declined to baseline. Immediate early gene expression was diminished by co-injection of L-AP3 and was not elicited by intraseptal injection of L-AP4, cysteine sulfinic acid or DHPG. Immediate early gene expression was not diminished by chronic lithium treatment but was diminished by chronic treatment with the phospholipase A(2) inhibitor quinacrine. Co-injection of the phospholipase A(2) inhibitor NDGA partially suppressed the induction of immediate early gene expression. Metabotropic glutamate receptors regulate lateral septal neuron excitability in vivo and some of their effects may be mediated by activation of phospholipase A(2). Alternatively, arachidonic acid may play a permissive role in the effects of metabotropic glutamate receptors on lateral septal neurons.

Animals↗
PubMed1996

Presynaptic monoaminergic vesicles in Parkinson's disease and normal aging.

We present development and human application of a method for determining the regional cerebral density of the type 2 vesicular monoamine transporter (VMAT2) using positron emission tomography (PET) and [11C]dihydrotetrabenazine (DTBZ). Previous animal studies indicate striatal VMAT2 density is linearly related to the integrity of substantia nigra dopamine neurons and is not subject to drug- or lesion-compensatory regulation. In the present studies, kinetic compartmental modeling was employed to estimate blood-brain [11C]DTBZ transport (K1) and VMAT2 binding site density (tissue-to-plasma DTBZ distribution volume, DV) from the cerebral and plasma DTBZ time courses after intravenous tracer injection. In controls, we found reductions of putamen DTBZ DVwith advancing age, corresponding to losses of 0.77% per year in specific VMAT2 binding. Parkinson's disease (PD) patients had reduction in specific DTBZ DV in the putamen (-61%) and in the caudate nucleus (-43%). There was no overlap of lowest specific putamen DTBZ DV between individual elderly controls and PD patients. The present results indicate the suitability of [11C]DTBZ PET for objective quantification of nigrostriatal integrity, including evaluation of PD progression and its possible therapeutic modification.

Adult↗
PubMed1996

GABAA receptor binding in the aging rat inferior colliculus.

The inhibitory neurotransmitter GABA has been shown to be critically involved in shaping neuronal responses to simple and complex acoustic stimuli in the inferior colliculus. Studies in the rat and human inferior colliculus have suggested significant changes in functions related to GABA neurotransmission occur in the aged. These changes include significant decreases in GABA content, GABA release, GABA neurons, glutamate decarboxylase enzymatic activity, and GABAB receptor binding. Such changes within the inferior colliculus may affect the ability of elderly listeners to process complex acoustic signals, particularly in the presence of background noise. The present study was designed to examine the regional distribution and effects of aging on GABAA receptor binding sites in the Fischer 344 rat inferior colliculus using in vitro quantitative receptor autoradiography. [3H]GABA binding to GABAA receptors was significantly reduced in the inferior colliculus of young adult (3 months) and aged (18-26 months) rats when compared to 2-month animals. However, no significant changes were observed after 3 months of age. Single concentrations of tritiated GABAA receptor ligands (muscimol, t-butylbicycloorthobenzoate, and flunitrazepam) revealed no significant age-related changes in receptor binding in the inferior colliculus between 3 and 26 months of age. To characterize further the pharmacology of the GABAA receptor in the inferior colliculus, GABA modulation of the picrotoxin binding site was examined using [3H]t-butylbicycloorthobenzoate. When increasing concentrations of GABA were added to the incubation buffer, a significant decrease in binding was observed in the inferior colliculus of rats in each age group. In aged rats, the dose-response curve was shifted to the left, indicating an increase in the potency of GABA to inhibit [3H]t-butylbicycloorthobenzoate binding. Although no changes in GABAA receptor binding were detected in the inferior colliculus after 3 months of age, a significant alteration in interaction between the GABA and picrotoxin binding sites was observed in the inferior colliculus of aged rats when compared to 3-month-old young adults. This difference appears to reflect an increased sensitivity of the receptor to GABA modulation in aged rats and, thus, may serve as a compensatory mechanism to enhance GABAA receptor function in response to a presynaptic loss of inhibition.

Aged↗
PubMed1996

Splice variants of glutamate receptor subunits 2 and 3 in striatal projection neurons.

The distribution of glutamate receptor subunits (GluR) 2 and 3 in relation to striatal efferent neurons was examined. Our results showed that striatonigral and striatopallidal neurons differed in the relative proportion of splice variant messenger RNAs expressed. The rank order of the percentage of striatonigral neurons expressing a particular splice variant was GluR2-flop (approximately 40%) > GluR3-flop (approximately 20%) > GluR2-flip (approximately 10-15%) > GluR3-flip (approximately 10%). For striatopallidal neurons, the pattern of expression was GluR3-flop (approximately 35%) > GluR2-flop (approximately 20%) > GluR3-flip (approximately 15-20%) > GluR2-flip (< 10%). By immunohistochemical methods, we observed that approximately half of striatal projection neurons stained for GluR2/4, with no discernible difference in the distribution or proportion of striatonigral neurons labeled as compared to striatopallidal neurons. In the case of striatonigral neurons, the immunohistochemical data support the results of in situ hybridization studies. However, with regard to striatopallidal neurons, the percentage of neurons expressing GluR2 messenger RNA (< 35%) is lower than the percentage of neurons expressing the receptor protein (approximately 50%). This disparity underscores the importance of looking at both messenger RNA expression and protein abundance rather than relying on a single measure of receptor expression. The results of in situ hybridization and immunohistochemical studies demonstrate inhomogeneity within both striatonigral and striatopallidal neuron populations since some, but not all, of these neurons express GluR2 and/or GluR3. These data suggest that specific populations of striatal projection neurons express unique complements of excitatory amino acid receptors, which may be important in the understanding of both normal striatal function and basal ganglia disease.

Alternative Splicing↗
PubMed1996

Chronic intrastriatal administration of quinolinic acid produces transient nocturnal hypermotility in the rat.

Adult male Sprague-Dawley rats were exposed to 15 mM quinolinic acid solution or vehicle via bilateral intrastriatal dialytic administration for a period of 3 weeks. Animals were tested twice weekly for spontaneous behaviors and nocturnal activity during the 3-week dialysis period and for the 3 weeks following cessation of the dialysis period treatment. Nocturnal activity increased significantly (p < 0.005) during the first week of quinolinic acid exposure compared to vehicle exposed animals. The increase in nocturnal activity subsequently diminished to near control levels by the end of the 3-week dialysis period. During the 3-week period following cessation of dialysis, no significant differences were seen between quinolinic acid and vehicle-exposed animals. In addition, no differences were noted between quinolinic acid and vehicle-exposed animals in spontaneous behaviors either in the 3-week dialysis period or the 3-week period following cessation of dialysis. The results of this study are in agreement with other recent findings of transient nocturnal hyperactivity following striatal damage in rats. One possible explanation for the transient nature of this behavioral change is a transient effect of excitotoxicity in the striatum. During initial exposure to excitotoxins, nocturnal hypermotility could result from premorbid changes in neural function. With continued exposure, this behavioral effect may then diminish as a result of subsequent widespread striatal cell death.

Animals↗
PubMed1996

Fluoro-deoxyglucose positron emission tomography in diffuse Lewy body disease.

We report six demented individuals with pathologically verified diffuse Lewy body disease (DLBD) studied with fluoro-deoxyglucose positron emission tomography (FDG-PET). Three subjects had pure DLBD and three subjects had combined DLBD and Alzheimer's disease (DLBD-AD) pathology. FDG-PET revealed evidence of diffuse cerebral hypometabolism in both pure DLBD and DLBD-AD with marked declines in association cortices with relative sparing of subcortical structures and primary somatomotor cortex, a pattern reported previously in AD. Unlike AD, however, these subjects also had hypometabolism in the occipital association cortex and primary visual cortex. These findings indicate the presence of diffuse cortical abnormalities in DLBD and suggest that FDG-PET may be useful in discriminating DLBD from AD antemortem.

Aged↗
PubMed1996

Felbamate inhibits [3H]t-butylbicycloorthobenzoate (TBOB) binding and enhances Cl- current at the gamma-aminobutyric AcidA (GABAA) receptor.

We investigated the interaction of felbamate (FBM) with gamma-aminobutyric acid type A receptors using receptor autoradiography with [3H]t-butylbicycloorthobenzoate (TBOB) and whole-cell patch-clamp recordings of cultured mouse cortical neurons. FBM produced dose-dependent inhibition of [3H]T-BOB binding with IC50 values of approximately 250 microM. Saturation analysis in the presence of FBM revealed increased Kd and decreased Bmax. Dissociation initiated by picrotoxin (PTX) was accelerated by FBM. The regional pattern of [3H]TBOB binding inhibition by FBM was different from the regional modulation of [3H]TBOB binding produced by gamma-aminobutyric acid (GABA) agonists, bicuculline, zinc or neurosteroids. With electrophysiological recordings, FBM enhanced GABA-elicited Cl- currents at GABA concentrations of 10 microM but not 3 microM or 100 microM. FBM enhancement was not blocked by the benzodiazepine antagonist flumazenil, and FBM did not affect pentobarbital potentiation of GABA-elicited currents. FBM also had no effect on PTX inhibition of GABA-elicited Cl- currents. These results suggest that FBM potentiates gamma-aminobutyric acid type A receptor function, at least in part, by acting at a site that interacts with the PTX site but is distinct from the PTX, barbiturate, GABA, benzodiazepine, zinc and neurosteroid sites.

Animals↗
PubMed1995

Adenosine A2 receptor-mediated modulation of contralateral rotation induced by metabotropic glutamate receptor activation.

Systemic pretreatment with the adenosine receptor antagonist theophylline significantly decreases contralateral rotation induced by unilateral intrastriatal 1-aminocyclopentane-1S,3R-dicarboxylic acid (1S,3R-ACPD). Intrastriatal or intrasubthalamic nucleus coadministration of theophylline and 1S,3R-ACPD significantly decreases contralateral rotation suggesting that metabotropic glutamate (mGlu) receptors and adenosine receptors interact locally. These appear to be adenosine A2 receptor effects as the adenosine A2 receptor antagonist 8-(3-chlorostyryl)caffeine (CSC) also decreases contralateral rotation induced by unilateral intrastriatal and intrasubthalamic nucleus administration of 1S,3R-ACPD, while the adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) has no effect. Pretreatment with the adenosine A2 receptor agonist 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamido adenosine hydrochloride (CGS 21680) potentiates contralateral rotation induced by unilateral striatal 1S,3R-ACPD, whereas pretreatment with the adenosine A1 receptor agonist N6-cyclopentyl-adenosine (CPA) has no effect. These results suggest that mGlu receptor effects may be due, in part, to modulation of adenosine action.

Animals↗