Biomedical subjects

M S Levine

Publications and source records attributed to M S Levine.

At least 19 recordsLinked to original sources

PubMed2006

Behavioral effects of dopaminergic agonists in transgenic mice overexpressing human wildtype alpha-synuclein.

Overexpression of alpha-synuclein causes familial Parkinson's disease and abnormal aggregates of the protein are present in sporadic cases of the disease. We have examined the behavioral effects of direct and indirect dopaminergic agonists in transgenic mice expressing human alpha-synuclein under the Thy-1 promoter (Thy1-aSyn, alpha-synuclein overexpressor), which exhibit progressive impairments in behavioral tests sensitive to nigrostriatal dopamine dysfunction. Male Thy1-aSyn and wild-type mice received vehicle, benserazide/L-DOPA (25 mg/kg, i.p.), high (2 mg/kg, s.c.) and low doses (0.125, 0.25, 0.5 mg/kg, s.c.) of apomorphine, and amphetamine (5 mg/kg, i.p.), beginning at 3 months of age, and were tested on the challenging beam, spontaneous activity, pole test, and gait. l-DOPA had a paradoxical effect and worsened the deficits in Thy1-aSyn mice compared with controls, whereas the high dose of apomorphine only produced few deficits above those already present in Thy1-aSyn. In contrast to wild-type mice, Thy1-aSyn mice did not show amphetamine-induced stereotypies. The results indicate that chronic overexpression of alpha-synuclein led to abnormal pharmacological responses in mice.

Amphetamine↗

PubMed2005

Early behavioral deficits in R6/2 mice suitable for use in preclinical drug testing.

Huntington's disease (HD) is a neurodegenerative disorder caused by an elongated glutamine repeat in huntingtin. Improved understanding of the molecular effects of the mutation opens new avenues for treatment. High-throughput automated behavioral tests that produce well-defined markers of disease progression are necessary for in vivo drug screening. We have identified early behavioral deficits in tests of motor function that are amenable to cost effective automated analysis in a mouse model of HD. Running wheel activity and climbing behavior were reduced in R6/2 HD transgenics from as early as 4.5 weeks of age, at a time when rotarod performance and grip strength were still normal. Power calculations showed that the running wheel test was appropriate for efficient, high-throughput drug screening at this early age. Furthermore, the data extend the range of behavioral deficits observed in 1-month-old R6/2 mice, an age when synaptic dysfunction can already be detected in the striatum.

Age Factors↗

PubMed2005

Transient failure of opening of the lower oesophageal sphincter on upright oesophagrams: radiographic and clinical findings.

The purpose of our study was to determine the frequency, radiographic features, and clinical importance of transient failure of opening of the lower oesophageal sphincter (LOS) on upright double-contrast views of the oesophagus. A computerized search of radiology records identified 16 patients who had transient failure of opening of the LOS on upright views from biphasic oesophagrams or upper gastrointestinal tract examinations using high-density barium but normal opening of the LOS on prone views using low-density barium. The radiographic findings were reviewed and correlated with the clinical and manometric findings. In all cases, barium studies revealed tapered, beaklike narrowing of the distal oesophagus on upright double-contrast views, with a normal-appearing distal oesophagus, normal opening of the LOS, and intact peristalsis on prone single-contrast views. Only seven patients (44%) had dysphagia. Five of these patients had clinical follow-up, and the dysphagia improved or resolved without specific treatment for LOS dysfunction in four. The remaining patient had persistent dysphagia, but this individual had polymyositis as the likely cause for his dysphagia. Manometry revealed incomplete relaxation of the LOS in two patients and normal relaxation in one. Our experience suggests that failure of opening of the LOS may be observed as a transient finding of little clinical importance on upright double-contrast views of the oesophagus using high-density barium, with normal opening of the LOS on prone single-contrast views using low-density barium. It is important to be aware of this finding, so that it is not mistaken for achalasia or other abnormalities of the distal oesophagus.

Adult↗

PubMed2004

Barrett esophagus: update for radiologists.

Barrett esophagus is a well-recognized entity in which there is progressive columnar metaplasia of the lower esophagus due to longstanding gastroesophageal reflux and reflux esophagitis [1]. This condition is important because it is associated with an increased risk of developing esophageal adenocarcinoma by a well-established sequence from dysplasia to carcinoma [2]. During the past decade, however, an explosion of new data has dramatically affected our understanding of Barrett esophagus. Not only have revised histopathologic criteria been developed for this condition, but it is currently believed that patients with Barrett esophagus should be classified as having "short-segment" or "long-segment" disease based on the extent of columnar metaplasia in the distal esophagus. This distinction has important implications for the risk of developing esophageal adenocarcinoma and subsequent need for endoscopic surveillance. The purpose of this article is to present these new concepts about Barrett esophagus and provide radiologists with a more current framework for diagnosing this condition.

Barrett Esophagus↗

PubMed2004

Laparoscopic Heller myotomy and fundoplication: findings and predictive value of early postoperative radiographic studies.

BACKGROUND: We describe the findings on esophagography, the frequency and appearance of leaks after laparoscopic Heller myotomy and fundoplication, and the utility of early postoperative studies for predicting clinical outcome. METHODS: Our study group consisted of 40 patients who underwent laparoscopic Heller myotomy and fundoplication in whom radiographic studies were performed during the early postoperative period. The radiographic reports and images were reviewed to determine the esophageal diameter, visualization or nonvisualization of the wrap, and the presence or absence of a leak. The esophageal diameter subsequently was correlated with the clinical findings to determine whether this was a useful parameter for predicting clinical outcome. RESULTS: Two patients (5%) had small, sealed-off leaks on radiographic studies, and four (10%) had pseudo-leaks resulting from trapping of contrast material alongside the fundoplication wrap. Twelve (60%) of 20 patients with a dilated esophagus had esophageal symptoms on short-term follow-up versus three (15%) of 20 with a normal-caliber esophagus (p = 0.008), and five (56%) of nine patients with a dilated esophagus had symptoms on long-term follow-up versus six (43%) of 14 with a normal-caliber esophagus (p = 0.68). CONCLUSION: Radiographic studies are useful for showing leaks after laparoscopic Heller myotomy and fundoplication, but radiologists should differentiate true leaks from trapping of contrast material alongside the fundoplication wrap. The caliber of the esophagus on early postoperative studies is also a useful parameter for predicting short-term clinical outcome in these patients.

Esophageal Achalasia↗

PubMed2004

Calcium modulates dopamine potentiation of N-methyl-D-aspartate responses: electrophysiological and imaging evidence.

In the striatum, dopamine (DA) exerts a major modulatory influence on voltage- and ligand-gated currents. Previously we have shown that DA modulates glutamatergic neurotransmission and that the direction of this modulation depends on, among other factors, the glutamate and DA receptor subtypes activated. These effects also involve DA-induced alterations in voltage-gated Ca(2+) currents. In the present experiments, the effects of Ca(2+) channel blockers on DA and D1 receptor-dependent potentiation of N-methyl-D-aspartate (NMDA) responses were examined in vitro in striatal slices using current clamp recording techniques. DA or D1 receptor agonists consistently enhanced NMDA responses. Cadmium and the more selective L-type Ca(2+) channel antagonists nifedipine and methoxyverapamil reduced the potentiation of NMDA responses by DA or D1 receptor activation. Furthermore, studies using Ca(2+) imaging with Fluo-3 in cultured cortical or dissociated striatal neurons demonstrated that DA and D1 agonists increased intracellular Ca(2+) transients induced by NMDA. These as well as previous findings indicate that in striatal neurons at least two mechanisms contribute to the enhancement of NMDA responses by DA receptor activation, facilitation of voltage-gated Ca(2+) currents and D1 receptor activation of the cAMP-protein kinase A cascade. The existence of multiple mechanisms leading to a similar outcome allows a certain degree of redundancy in the consequences of DA modulation.

Age Factors↗

PubMed2004

Detection of reflux esophagitis on double-contrast esophagrams and endoscopy using the histologic findings as the gold standard.

The purpose of our study was to determine the accuracy of double-contrast barium studies and endoscopy for detecting reflux esophagitis, using the endoscopic biopsy findings as the gold standard. A review of radiology, endoscopy, and pathology files showed 37 patients with reflux symptoms who underwent double-contrast barium studies and endoscopy with biopsy specimens from the esophagus. The radiographic images were reviewed in a blinded fashion and correlated with the endoscopic and histologic findings to determine the radiographic and endoscopic accuracies for detecting reflux esophagitis, using the endoscopic biopsy specimens as the gold standard. Double-contrast barium studies and endoscopy had low but comparable accuracies for detecting reflux esophagitis, with sensitivities of 35% and 39%, specificities of 79% and 71%, positive predictive values of 73% and 69%, and negative predictive values of 42% and 41%, respectively. When mucosa granularity was evaluated as an individual sign of esophagitis on double-contrast studies, this finding had a sensitivity of 35%, a specificity of 93%, a positive predictive value of 89%, and a negative predictive value of 46% for detecting reflux esophagitis. Our experience suggests that double-contrast barium studies and endoscopy have limited ability to detect reflux esophagitis, in particular mild esophagitis, when using the histologic findings as the gold standard. When radiographic abnormalities are detected, however, mucosal granularity is the single best sign of reflux esophagitis on double-contrast studies.

Adult↗

PubMed2004

Endogenous opioids mediate basal hedonic tone independent of dopamine D-1 or D-2 receptor activation.

Exogenously administered opiates are recognized as rewarding and the involvement of dopamine systems in mediating their apparent pleasurable effects is contentious. The aversive response to naloxone administration observed in animal studies suggests the presence of an endogenous opioid tone regulating hedonic state. We sought evidence for the requirement for dopamine systems in mediating this action of endogenous opioids by determining whether mice deficient in dopamine D-1 or D-2 receptors were able to display conditioned place aversion to naloxone. Mice received saline in the morning in one chamber and either saline or naloxone (10 mg/kg, s.c.) in the afternoon in another chamber, each day for 3 days. On the test day they were given free access to the testing chambers in the afternoon. Similar to their wild-type littermates, D-1 and D-2 receptor knockout mice receiving naloxone in the afternoon spent significantly less time on the test day in the compartment in which they previously received naloxone, compared with animals receiving saline in the afternoon. The persistence of naloxone-conditioned place aversion in D-1 and D-2 knockout mice suggests that endogenous opioid peptides maintain a basal level of positive affect that is not dependent on downstream activation of dopamine systems involving D-1 or D-2 receptors.

Affect↗

PubMed2002

Radiographically diagnosed antral gastritis: findings in patients with and without Helicobacter pylori infection.

The purpose of this study was to characterize the radiographic findings of antral gastritis and to determine whether there are differences in the appearance of antral gastritis in patients with and without Helicobacter pylori infection. A search of radiology, endoscopy and pathology files revealed 90 patients with antral gastritis on double contrast upper gastrointestinal tract studies who had endoscopy with testing for H. pylori. The barium studies were evaluated to further characterize the findings of antral gastritis without knowledge of the H. pylori status of the patients or of the endoscopy or pathology findings. The radiographic findings of antral gastritis included thickened folds in 67 patients (74%), polypoid antral gastritis (a subset of patients with thickened folds) in 6 (9%), antral erosions in 21 (23%), enlarged areae gastricae in 14 (16%), crenulation of the lesser curvature in 4 (4%), mucosal nodularity in 2 (2%), a hypertrophied antral-pyloric fold in 2 (2%) and antral striae in 1 (1%). 43 patients (48%) with antral gastritis were H. pylori positive and 47 patients (52%) were H. pylori negative. Thickened folds were detected in 39 H. pylori-positive patients (91%) with antral gastritis vs 28 H. pylori-negative patients (60%) (p<0.001); polypoid gastritis in 6 H. pylori-positive patients (14%) vs 0 H. pylori-negative patients (p<0.05); enlarged areae gastricae in 14 H. pylori-positive patients (33%) vs 0 H. pylori-negative patients (p<0.0001); and antral erosions in 2 H. pylori-positive patients (5%) vs 19 H. pylori-negative patients (40%) (p<0.0001). Our experience suggests that antral gastritis caused by H. pylori infection is associated with characteristic features on double contrast studies (including thickened folds, polypoid gastritis and enlarged areae gastricae) and that this condition is rarely associated with antral erosions. Thus, radiologists can often suggest whether the patient's gastritis is caused by H. pylori on the basis of radiographic findings.

Adult↗

PubMed2001

Changes in cortical and striatal neurons predict behavioral and electrophysiological abnormalities in a transgenic murine model of Huntington's disease.

Neurons in Huntington's disease exhibit selective morphological and subcellular alterations in the striatum and cortex. The link between these neuronal changes and behavioral abnormalities is unclear. We investigated relationships between essential neuronal changes that predict motor impairment and possible involvement of the corticostriatal pathway in developing behavioral phenotypes. We therefore generated heterozygote mice expressing the N-terminal one-third of huntingtin with normal (CT18) or expanded (HD46, HD100) glutamine repeats. The HD mice exhibited motor deficits between 3 and 10 months. The age of onset depended on an expanded polyglutamine length; phenotype severity correlated with increasing age. Neuronal changes in the striatum (nuclear inclusions) preceded the onset of phenotype, whereas cortical changes, especially the accumulation of huntingtin in the nucleus and cytoplasm and the appearance of dysmorphic dendrites, predicted the onset and severity of behavioral deficits. Striatal neurons in the HD mice displayed altered responses to cortical stimulation and to activation by the excitotoxic agent NMDA. Application of NMDA increased intracellular Ca(2+) levels in HD100 neurons compared with wild-type neurons. Results suggest that motor deficits in Huntington's disease arise from cumulative morphological and physiological changes in neurons that impair corticostriatal circuitry.

Age of Onset↗

PubMed2001

NMDA receptor function in mouse models of Huntington disease.

Huntington disease (HD) is an autosomal dominant disorder in which degeneration of medium-sized spiny striatal neurons occurs. The HD gene and the protein it encodes, huntingtin, have been identified but their functions remain unknown. Transgenic mouse models for HD have been developed and we examined responses of medium-sized striatal neurons recorded in vitro to application of N-methyl-D-aspartate (NMDA) in two of these. The first model (R6/2) expresses exon 1 of the human HD gene with approximately 150 CAG repeats. In the R6/2 an enhancement of currents induced by selective activation of NMDA receptors as well as an enhancement of intracellular Ca(2+) flux occurred in both presymptomatic and symptomatic mice. These alterations appeared specific for the NMDA receptor because alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor-mediated currents were reduced in symptomatic R6/2s. In R6/2 animals there were parallel increases in NMDA-R1 and decreases in NMDA-R2A/B subunit proteins as established by immunohistochemistry. The second model (YAC72) contains human genomic DNA spanning the full-length gene and all its regulatory elements with 72 CAG repeats. The phenotypical expression of the disorder develops more gradually than in the R6/2. In YAC72 mice we found similar but less marked increases in responses of medium-sized striatal neurons to NMDA. These findings indicate that alterations in NMDA receptor function may predispose striatal neurons to excitotoxic damage, leading to subsequent neuronal degeneration and underscore the functional importance of NMDA receptors in HD.

Animals↗

PubMed2001

Dopamine D4 receptor-deficient mice display cortical hyperexcitability.

The dopamine D(4) receptor (D(4)R) is predominantly expressed in the frontal cortex (FC), a brain region that receives dense input from midbrain dopamine (DA) neurons and is associated with cognitive and emotional processes. However, the physiological significance of this dopamine receptor subtype has been difficult to explore because of the slow development of D(4)R agonists and antagonists the selectivity and efficacy of which have been rigorously demonstrated in vivo. We have attempted to overcome this limitation by taking a multidimensional approach to the characterization of mice completely deficient in this receptor subtype. Electrophysiological current and voltage-clamp recordings were performed in cortical pyramidal neurons from wild-type and D(4)R-deficient mice. The frequency of spontaneous synaptic activity and the frequency and duration of paroxysmal discharges induced by epileptogenic agents were increased in mutant mice. Enhanced synaptic activity was also observed in brain slices of wild-type mice incubated in the presence of the selective D(4)R antagonist PNU-101387G. Consistent with greater electrophysiological activity, nerve terminal glutamate density associated with asymmetrical synaptic contacts within layer VI of the motor cortex was reduced in mutant neurons. Taken together, these results suggest that the D(4)R can function as an inhibitory modulator of glutamate activity in the FC.

4-Aminopyridine↗

PubMed2001

CtBP-dependent activities of the short-range Giant repressor in the Drosophila embryo.

There are at least three short-range gap repressors in the precellular Drosophila embryo: Krüppel, Knirps, and Giant. Krüppel and Knirps contain related repression motifs, PxDLSxH and PxDLSxK, respectively, which mediate interactions with the dCtBP corepressor protein. Here, we present evidence that Giant might also interact with dCtBP. The misexpression of Giant in ventral regions of transgenic embryos results in the selective repression of eve stripe 5. A stripe5-lacZ transgene exhibits an abnormal staining pattern in dCtBP mutants that is consistent with attenuated repression by Giant. The analysis of Gal4-Giant fusion proteins identified a minimal repression domain that contains a sequence motif, VLDLS, which is conserved in at least two other sequence-specific repressors. Removal of this sequence from the native Giant protein does not impair its repression activity in transgenic embryos. We propose that Giant-dCtBP interactions might be indirect and mediated by an unknown bZIP subunit that forms a heteromeric complex with Giant. We also suggest that the VLDLS motif recruits an as yet unidentified corepressor protein.

Alcohol Oxidoreductases↗

PubMed2001

Fecal impaction: a cause of isolated small bowel dilatation on abdominal radiographs.

OBJECTIVE: The purpose of this study was to assess the frequency of isolated small bowel dilatation on abdominal radiographs in patients with colonic fecal impaction and also to elucidate the cause of this finding. METHODS: A computerized search of radiology files revealed 515 patients with colonic fecal impaction on abdominal radiographs. The radiologic reports described isolated small bowel dilatation not related to other known causes of ileus or obstruction in 18 (3.5%) of the 515 patients. The films were reviewed to determine the distribution of fecal impaction and the degree and extent of small bowel dilatation. In 16 cases, medical records were reviewed to determine the clinical presentation, treatment, and course. Finally, follow-up radiographs were reviewed in four cases to determine the response to treatment of the impaction. RESULTS: All 16 patients with available medical records had abdominal symptoms. The average diameter of the dilated small bowel on abdominal radiographs was 3.7 cm. Fourteen patients (78%) had a diffuse colonic fecal impaction (nine) or a predominantly right-sided fecal impaction (five) that involved the cecum, and the remaining four (22%) had a left-sided colonic fecal impaction. All 12 patients with clinical follow-up had resolution of symptoms and all four with follow-up radiographs had resolution of small bowel dilatation after treatment of the underlying impaction. CONCLUSION: Fecal impaction should be considered in the differential diagnosis of small bowel dilatation on abdominal radiographs, as treatment of the underlying impaction usually produces a dramatic clinical response with resolution of the small bowel dilatation on follow-up radiographs.

Adult↗

PubMed2001

Differential sensitivity of medium- and large-sized striatal neurons to NMDA but not kainate receptor activation in the rat.

Infrared videomicroscopy and differential interference contrast optics were used to identify medium- and large-sized neurons in striatal slices from young rats. Whole-cell patch-clamp recordings were obtained to compare membrane currents evoked by application of N-methyl-d-aspartate (NMDA) and kainate. Inward currents and current densities induced by NMDA were significantly smaller in large- than in medium-sized striatal neurons. The negative slope conductance for NMDA currents was greater in medium- than in large-sized neurons and more depolarization was required to remove the Mg2+ blockade. In contrast, currents induced by kainate were significantly greater in large-sized neurons whilst current densities were approximately equal in both cell types. Spontaneous excitatory postsynaptic currents occurred frequently in medium-sized neurons but were relatively infrequent in large-sized neurons. Excitatory postsynaptic currents evoked by electrical stimulation were smaller in large- than in medium-sized neurons. A final set of experiments assessed a functional consequence of the differential sensitivity of medium- and large-sized neurons to NMDA. Cell swelling was used to examine changes in somatic area in both neuronal types after prolonged application of NMDA or kainate. NMDA produced a time-dependent increase in somatic area in medium-sized neurons whilst it produced only minimal changes in large interneurons. In contrast, application of kainate produced significant swelling in both medium- and large-sized cells. We hypothesize that reduced sensitivity to NMDA may be due to variations in receptor subunit composition and/or the relative density of receptors in the two cell types. These findings help define the conditions that put neurons at risk for excitotoxic damage in neurological disorders.

Animals↗

PubMed2001

Facilitated glutamatergic transmission in the striatum of D2 dopamine receptor-deficient mice.

Dopamine (DA) receptors play an important role in the modulation of excitability and the responsiveness of neurons to activation of excitatory amino acid receptors in the striatum. In the present study, we utilized mice with genetic deletion of D2 or D4 DA receptors and their wild-type (WT) controls to examine if the absence of either receptor subtype affects striatal excitatory synaptic activity. Immunocytochemical analysis verified the absence of D2 or D4 protein expression in the striatum of receptor-deficient mutant animals. Sharp electrode current- and whole cell patch voltage-clamp recordings were obtained from slices of receptor-deficient and WT mice. Basic membrane properties were similar in D2 and D4 receptor-deficient mutants and their respective WT controls. In current-clamp recordings in WT animals, very little low-amplitude spontaneous synaptic activity was observed. The frequency of these spontaneous events was increased slightly in D2 receptor-deficient mice. In addition, large-amplitude depolarizations were observed in a subset of neurons from only the D2 receptor-deficient mutants. Bath application of the K+ channel blocker 4-aminopyridine (100 microM) and bicuculline methiodide (10 microM, to block synaptic activity due to activation of GABA(A) receptors) markedly increased spontaneous synaptic activity in receptor-deficient mutants and WTs. Under these conditions, D2 receptor-deficient mice displayed significantly more excitatory synaptic activity than their WT controls, while there was no difference between D4 receptor-deficient mice and their controls. In voltage-clamp recordings, there was an increase in frequency of spontaneous glutamate receptor-mediated inward currents without a change in mean amplitude in D2 receptor-deficient mutants. In WT mice, activation of D2 family receptors with quinpirole decreased spontaneous excitatory events and conversely sulpiride, a D2 receptor antagonist, increased activity. In D2 receptor-deficient mice, sulpiride had very little net effect. Morphologically, a subpopulation of medium-sized spiny neurons from D2 receptor-deficient mice displayed decreased dendritic spines compared with cells from WT mice. These results provide evidence that D2 receptors play an important role in the regulation of glutamate receptor-mediated activity in the corticostriatal or thalamostriatal pathway. These receptors may function as gatekeepers of glutamate release or of its subsequent effects and thus may protect striatal neurons from excessive excitation.

4-Aminopyridine↗

PubMed2001

Electrophysiological and morphological changes in striatal spiny neurons in R6/2 Huntington's disease transgenic mice.

We examined passive and active membrane properties and synaptic responses of medium-sized spiny striatal neurons in brain slices from presymptomatic (approximately 40 days of age) and symptomatic (approximately 90 days of age) R6/2 transgenics, a mouse model of Huntington's disease (HD) and their age-matched wild-type (WT) controls. This transgenic expresses exon 1 of the human HD gene with approximately 150 CAG repeats and displays a progressive behavioral phenotype associated with numerous neuronal alterations. Intracellular recordings were obtained using standard techniques from R6/2 and age-matched WT mice. Few electrophysiological changes occurred in striatal neurons from presymptomatic R6/2 mice. The changes in this age group were increased neuronal input resistance and lower stimulus intensity to evoke action potentials (rheobase). Symptomatic R6/2 mice exhibited numerous electrophysiological alterations, including depolarized resting membrane potentials, increased input resistances, decreased membrane time constants, and alterations in action potentials. Increased stimulus intensities were required to evoke excitatory postsynaptic potentials (EPSPs) in neurons from symptomatic R6/2 transgenics. These EPSPs had slower rise times and did not decay back to baseline by 45 ms, suggesting a more prominent component mediated by activation of N-methyl-D-aspartate receptors. Neurons from both pre- and symptomatic R6/2 mice exhibited reduced paired-pulse facilitation. Data from biocytin-filled or Golgi-impregnated neurons demonstrated decreased dendritic spine densities, smaller diameters of dendritic shafts, and smaller dendritic fields in symptomatic R6/2 mice. Taken together, these findings indicate that passive and active membrane and synaptic properties of medium-sized spiny neurons are altered in the R6/2 transgenic. These physiological and morphological alterations will affect communication in the basal ganglia circuitry. Furthermore, they suggest areas to target for pharmacotherapies to alleviate and reduce the symptoms of HD.

Action Potentials↗

PubMed2001

Metabotropic glutamate receptors mGluR1alpha and mGluR2/3 display dynamic expression patterns in developing rat striatum.

The developmental expression of two metabotropic glutamate receptors (mGluR), mGluR1alpha and mGluR2/3 was evaluated in the rat striatum from birth to adulthood. The mGluR1alpha receptor subtype displayed a patchy organization perinatally that became more homogeneous after the first postnatal week. The adult pattern of receptor expression consisted of homogeneous punctate profiles spread throughout the striatum. The mGluR2/3 receptor subtype exhibited a unique pattern of ontogenic expression, being associated exclusively with fibers of the internal capsule that penetrate the striatum, during the perinatal period. The protein localization for this subtype spread into the striatal neuropil after the first postnatal week, in parallel to the development of afferent terminations and arborizations to the nucleus. Unlike the ionotropic GluR subunits that are associated with somata and dendrites, neither subtype of metabotropic receptor was associated with neuronal cell bodies within the striatum.

Animals↗