PubMed Health⌕ Search

Biomedical subjects

M S LeDoux

Publications and source records attributed to M S LeDoux.

At least 19 recordsLinked to original sources
PubMed2001

Regulation of the tyrosine hydroxylase and dopamine beta-hydroxylase genes by the transcription factor AP-2.

The retinoic acid-inducible and developmentally regulated transcription factor AP-2 plays an important role during development. In adult mammals, AP-2 is expressed in both neural and non-neural tissues. However, the function of AP-2 in different neuronal phenotypes is poorly understood. In this study, transcriptional regulation of tyrosine hydroxylase (TH) and dopamine beta-hydroxylase (DBH) genes by AP-2 was investigated. AP-2 binding sites were identified in the upstream regions of both genes. Electrophoretic mobility shift assays (EMSA) and DNase I footprinting analyses indicate that the AP-2 interaction with these motifs is more prominent in catecholaminergic SK-N-BE(2)C and CATH.a than in non-catecholaminergic HeLa and HepG2 cell lines. Exogenous expression of AP-2 robustly transactivated TH and DBH promoter activities in non-catecholaminergic cell lines. While AP-2 regulates the DBH promoter activity via a single site, transactivation of the TH promoter by AP-2 appears to require multiple sites. In support of this, mutation of multiple AP-2 binding sites but not that of single site diminished the basal promoter activity of the TH gene in cell lines that express TH and abolished transactivation by exogenous AP-2 expression in cell lines that do not express TH. In contrast, mutation of a single AP-2 binding site of the DBH gene completely abolished transactivation by AP-2. Double-label immunohistochemistry showed that AP-2 is coexpressed with TH in noradrenergic and adrenergic neurons in both the central and peripheral nervous systems of adult rodents. Numerous non-catecholaminergic cell groups within the spinal cord, medulla, cerebellum, and pons also express AP-2. The concentration of AP-2 in dorsomedial locations along the neuraxis suggests a regionally specific role for this transcription factor in the regulation of neuronal function. Based on these findings we propose that AP-2 may coregulate TH and DBH gene expression and thus participate in expression/maintenance of neurotransmitter phenotypes in (nor)adrenergic neurons and neuroendocrine cells.

Animals↗
PubMed2001

Parasympathetic innervation of the meibomian glands in rats.

PURPOSE: To determine the location of parasympathetic neurons that innervate the meibomian glands in rats. METHODS: The B subunit of cholera toxin (CTB), fast blue, and a retrograde transneuronal tracer, the Bartha strain of pseudorabies virus (PRV-Ba), were injected into the upper eyelids of adult Sprague-Dawley rats after sectioning the ipsilateral branches of the facial nerve and resecting the superior cervical ganglia. Brains and orbital tissues were processed for the immunohistochemical detection of PRV-Ba and CTB. In selected cases, series of brain sections were double labeled for PRV-Ba and tyrosine hydroxylase to determine the relationship between the A5 noradrenergic cell group and superior salivatory nucleus, or for PRV-Ba and choline acetyltransferase to establish the neurochemical phenotype of parasympathetic preganglionic neurons. RESULTS: Labeled ganglionic cells were diffusely distributed within the ipsilateral pterygopalatine ganglion (PPG) and along the more proximal portions of the greater petrosal nerve (GPN). Labeled preganglionic neurons were cholinergic and were located immediately dorsolateral to the rostral-most portion of the facial nucleus and caudal superior olive, where they intermingled with A5 noradrenergic cells. CONCLUSIONS: The meibomian glands and other structures within the lid margin are subject to parasympathetic regulation by ganglion cells diffusely distributed within the PPG and along more proximal portions of the GPN. Cholinergic parasympathetic preganglionic neurons that project to meibomian gland-innervating ganglion cells are located immediately lateral, dorsal, and rostral to the facial motor nucleus in the region commonly referred to as the superior salivatory nucleus.

Amidines↗
PubMed1998

Serotonergic modulation of eye blinks in cat and monkey.

Serotonergic modulation of spontaneous and reflexive blinking was studied in four cats and one monkey. In cats, facial nucleus injections of the type-2 serotonin receptor (5-HT2) antagonist ketanserin tended to increase the latency of the first (R1) and second (R2) components of the blink reflex to supraorbital nerve stimulation. Injections of serotonin tended to increase and of ketanserin, to decrease the duration and amplitude of R2. Serotonin also produced unilateral blepharospasm and hemifacial spasm. In the monkey, the 5-HT2 agonist 2,5-dimethoxy-4-iodoamphetamine increased spontaneous blink frequency while ketanserin decreased both peak blink velocity and spontaneous blink frequency. These findings in cat and monkey indicate that serotonergic innervation of the facial nucleus has a behaviorally important role in modulation of spontaneous and reflexive blinks and suggest that dysfunction of serotonergic systems could be important to the pathophysiology of some cases of blepharospasm.

Animals↗
PubMed1998

Single-unit activity of cerebellar nuclear cells in the awake genetically dystonic rat.

The purpose of this study was to characterize neuronal activity in the deep cerebellar nuclei of the unanesthetized genetically dystonic rat during the neonatal period when the clinical signs of the dystonic syndrome first appear. Previous lesion studies have established cerebellar output as critical to the expression of the dystonic rat's motor syndrome, a disorder that closely resembles generalized dystonia in humans. In the dystonic rat, both cerebellectomy and selective lesions of the deep cerebellar nuclei decrease the frequency of abnormal motor signs and improve performance on tests of motor function. Single-unit activity was recorded from the medial, interpositus and lateral cerebellar nuclei in awake normal (N=49) and dystonic (N=54) rats at postnatal days 12-26. One hundred and eighty-three cells were isolated, 91 from normal and 92 from dystonic rats. Interspike interval histograms, autocorrelations and ratemeter histograms were generated for each cell's spike train. Interspike interval histograms were modeled with single and double gamma distributions. Cells from dystonic rats as young as 12 days of age showed bursting firing patterns, positively skewed or bimodal interspike interval histograms, and sinusoidal autocorrelations. Bursting activity increased linearly with postnatal age in dystonic rats. Cells from normal rats demonstrated non-sinusoidal autocorrelations and unimodal interspike interval histograms. Spike frequency increased linearly with postnatal age in both normal and dystonic rats. There were no statistically significant group differences in spike frequency between normal and dystonic rats. These findings show that functional neuropathology can be detected at the level of single neurons in the deep cerebellar nuclei at the earliest behavioral stages of the dystonic rat's movement disorder. The degree of abnormality in spike train parameters correlates with the severity of the movement disorder. Independent of neuronal firing rates, abnormal neuronal firing patterns can serve as a guide to the localization of pathological cell populations within the central nervous system. These results provide additional evidence that abnormal cerebellar output plays a critical role in the pathophysiology of the dystonic rat's motor syndrome.

Aging↗
PubMed1997

Blink reflex to supraorbital nerve stimulation in the cat.

Neurophysiological studies of the blink reflex to supraorbital nerve stimulation were conducted in eight alert, adult male cats. The cat, like other mammals, shows both short-latency (R1) and long-latency (R2) orbicularis oculi electromyographic (OOemg) components. Measures of OOemg latency, duration, integrated area, and maximum amplitude (MA) were obtained at a stimulus magnitude of 1.5xR2 threshold. The mean (+/-SE) minimal latencies for R1 and R2 were 8.26+/-0.85 and 22.97+/-1.53 ms, respectively. On average, R1 MA was larger than R2 MA. R1 and R2 area measures were similar. Three stimulus paradigms were tested. In a paired-stimulus paradigm, the interstimulus interval (ISI) was randomly varied from 100 to 1200 ms. Ratios were constructed for the OOemg area and MA by dividing the test response by the conditioning response. In this paradigm, although a significant linear relationship was observed only between ISI and R2 MA, conditioning effects were noted on both R1 and R2 area and MA test responses at several ISIs. In a habituation paradigm, both R2 and R1 showed habituation at stimulus frequencies from 0.5 to 2 Hz. In a stimulus-response paradigm, stimulus magnitude was randomly varied between threshold and 2xthreshold. In this paradigm, OOemg area and MA of both R1 and R2 were linearly related to stimulus magnitude. Neither the systemically administered centrally acting alpha2-adrenergic antagonist yohimbine nor agonist clonidine had significant effects on blink reflex parameters, habituation, or the paired-stimulus paradigm. Overall, these results suggest that there are important similarities in the control and modulation of the R1 and R2 components of the blink reflex to supraorbital nerve stimulation in cats.

Adrenergic alpha-Agonists↗
PubMed1995

Selective elimination of cerebellar output in the genetically dystonic rat.

The genetically dystonic (dt) rat, an autosomal recessive mutant, exhibits a progressive motor syndrome that resembles the generalized idiopathic dystonia seen in humans. Even with supportive measures, dt rats die before reaching maturity. A total cerebellectomy that includes the dorsal portions of the lateral vestibular nuclei (dLV) eliminates the dystonic motor syndrome of the dt rats, greatly improves motor function, and prevents early death. The selective elimination of cerebellar nuclei was used to determine the cerebellar components critical to the mutant's motor syndrome. Bilateral electrolytic and/or excitatory amino acid lesions of the medial cerebellar nucleus, nucleus interpositus, lateral cerebellar nucleus and dLV were created in separate groups of 15-day-old dt rats. Rats were observed for the presence of abnormal motor signs (falls, twists, clasps, pivots) and tested on several measures of motor performance (activity, climbing, righting, homing, hanging) before surgery and again on Postnatal Day 20. All nuclear lesions produced significant improvements in motor function and decreases in the frequency of abnormal motor signs. Electrolytic lesions of the dLV were associated with the greatest improvements.

Animals↗
PubMed1995

SPECT abnormalities in generalized dystonia.

A patient with severe, generalized dystonia and 6 age range-matched controls were studied with the regional cerebral blood flow tracer technetium-99m hexamethylpropyleneamine oxime by single-photon emission computed tomography to test the hypothesis that cerebellar function is abnormal in dystonia. Analysis was performed by drawing regions of interest around the caudate head nuclei, hemithalami, deep cerebellar nuclei, and cerebellar hemicortices. The counts in each region of interest were normalized to whole brain cerebral blood flow in an identical manner for each subject. The dystonic patient had a difference in regional cerebral blood flow between the right and left deep cerebellar nuclei, increased regional cerebral blood flow in subcortical motor structures, and an abnormal relationship between right cerebellar cortical and right deep cerebellar nuclear regional cerebral blood flow. The findings in this patient provide evidence that the cerebellum may play a role in the pathophysiology of motor signs in some patients with dystonia.

Brain↗
PubMed1993

Cerebellectomy eliminates the motor syndrome of the genetically dystonic rat.

The genetically dystonic (dt) rat is a neurological mutant that displays a movement disorder characterized by repetitive twisting movements of the trunk and limbs. Previous work has identified the cerebellum of the dt rat as a site of biochemical, metabolic, and functional abnormality. In order to test the hypothesis that a cerebellar defect is critical to the expression of the motor syndrome, groups of dt rats and phenotypically normal littermates underwent cerebellectomy (CBX) at either 15 or 20 days of age. The performance of these animals on a battery of motor tasks was compared with their preoperative performance. Age-matched unoperated rats of the same phenotype and a group of dt rats with lesions in the entopeduncular nuclei (ENTO) served as controls. In dt rats, CBX permanently eliminated all motor signs of the disease except pivoting movements without reducing overall levels of activity. In the dt rats, CBX also caused significant improvement in several tests of motor function. The ENTO group, however, showed an increase in motor signs and no improvement in motor function. The results of this study provide the first evidence that the abnormalities detected in the cerebellum of the dt rat are causally related to the motor syndrome and suggest that abnormal cerebellar output may contribute to the expression of motor signs in some human dystonias.

Animals↗
PubMed1993

Spinal cord stimulation for the failed back syndrome.

Thirty-two patients with failed back syndrome received a trial of spinal cord stimulation. Stimulators were internalized in 26; long-term follow-up was available for 23 of these patients. Seventy-six percent of the 22 patients with stimulators still present at 1 year and 74% of the 19 patients with stimulators still present at 2 years were receiving 50% or better pain relief. Patients routinely underwent pain team evaluation and therapy, psychological testing and a transcutaneous electrical nerve stimulator trial prior to consideration of spinal cord stimulation. The most common complication was electrode migration. Spinal cord stimulation should be considered as an important therapeutic modality in carefully selected patients with failed back syndrome.

Electric Stimulation Therapy↗
PubMed1993

Lumbosacral neurenteric cyst in an infant. Case report.

The case of a combined intra- and extraspinal neurenteric cyst in an infant is reported. This case is unique because an intraspinal cyst was not suspected clinically until large numbers of squamous epithelial cells were obtained at lumbar puncture performed as part of a workup for a septic entity. The cyst extended from an intradural location ventral to the conus medullaris at L-1 through a ventrolateral defect in the S-4 vertebral body to communicate with a large presacral component. The entire cystic cavity was lined by stratified squamous epithelium. The possible pathogenesis of this lesion is discussed.

Humans↗
PubMed1991

Topographic distribution of connections from the primary motor cortex to the corpus striatum in Aotus trivirgatus.

Connections between the primary motor cortex (MI) and the corpus striatum were studied in the owl monkey. Representations of specific body movements were elicited in MI by microstimulation techniques, and the efferent projections from these stimulation sites were labeled with wheat germ agglutinin-horseradish peroxidase conjugate (WGA-HRP). Dense projections were found in the putamen ipsilateral to the injection site and sparser projections occupied comparable areas in the contralateral putamen. Representations of hindpaw regions projected to the dorsomedial portion of the putamen with only slight extensions across cell bridges into the caudate nucleus. Representations of the forepaw and head projected to progressively more ventrolateral zones of the dorsal two-thirds of the putamen. Projections from injections of cortex representing discrete body movements terminated in an irregular or patchy distribution over a relatively large portion of the putamen. Extensive projections from relatively discrete injections in MI are indicative of a large degree of divergence and provide evidence for possible overlap from representations of relatively disparate body parts. The results are consistent with observations reported in other species of primates, but different from those seen in carnivores. This difference is discussed with regard to possible general features of corticostriate organization.

Animals↗
PubMed1991

Stabilization of the cervical spine in spondyloepiphyseal dysplasia congenita.

Spondyloepiphyseal dysplasia congenita is an inheritable bone dysplasia causing abnormalities that manifest at birth and primarily involve the spine and proximal epiphyses. The clinical findings include short-trunk dwarfism, myopia, frequent retinal detachment, shortening of the spine and proximal extremities, mild thoracic kyphoscoliosis, a barrel-shaped thorax, a short neck, and mild ocular hypertelorism. The characteristic radiographic features are a generalized delay in ossification, flattening and dysplasia of the vertebral bodies, pelvic dysplasia, and retarded ossification of the femoral head and neck. Other radiographic features of interest to the neurosurgeon may be platybasia, kyphoscoliosis, lumbar hyperlordosis, and odontoid hypoplasia. A case of spondyloepiphyseal dysplasia congenita is presented in which an unstable and markedly dysplastic cervical spine was stabilized with Halifax interlaminar clamps and sublaminar wires. The clinical findings and radiographic features are presented and the etiology and neurosurgical management of spondyloepiphyseal dysplasia congenita are discussed.

Cervical Vertebrae↗