المؤلفون: Liliane Kappeler, André Schaller, C. Nguyen-Thi Xuan-Huong, J.F. Benoist, F. Seibold, K. Madhavi Vadday, Heinrich Mattle, Sabina Gallati, Jean-Marc Burgunder, Caspar Brekenfeld, W.M.M. Schüpbach

المصدر: Schüpbach, W; Vadday, K; Schaller, A; Brekenfeld, C; Kappeler, L; Benoist, JF; Xuan-Huong, C; Burgunder, J; Seibold, F; Gallati, S; Mattle, H (2007). Mitochondrial neurogastrointestinal encephalomyopathy in three siblings: clinical, genetic and neuroradiological features. Journal of neurology, 254(2), pp. 146-53. Heidelberg: Steinkopff-Verlag; www.steinkopff.springer.de 10.1007/s00415-006-0255-3 <http://dx.doi.org/10.1007/s00415-006-0255-3Test>

مصطلحات موضوعية: Adult, Male, medicine.medical_specialty, Pathology, Magnetic Resonance Spectroscopy, Neural Conduction, Biology, Ophthalmoparesis, Leukoencephalopathy, Mitochondrial myopathy, Mitochondrial Encephalomyopathies, Internal medicine, Diseases in Twins, medicine, Humans, Thymidine phosphorylase, Radionuclide Imaging, Myopathy, Gastrointestinal dysmotility, Thymidine Phosphorylase, medicine.diagnostic_test, Siblings, Magnetic resonance imaging, Exons, Sequence Analysis, DNA, medicine.disease, Magnetic Resonance Imaging, Corpus Striatum, Substantia Nigra, Endocrinology, Neurology, Mutation, Neurology (clinical), medicine.symptom, Polyneuropathy, Thymidine

الوصف: Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a rare autosomal recessive disorder in which a nuclear mutation of the thymidine phosphorylase (TP) gene causes mitochondrial genomic dysfunction. Patients suffer from gastrointestinal dysmotility, cachexia, ptosis, external ophthalmoparesis, myopathy and polyneuropathy. Magnetic resonance imaging (MRI) shows leukoencephalopathy. We describe clinical, genetic and neuroradiological features of three brothers affected with MNGIE. Clinical examination, laboratory analyses, MRI and magnetic resonance spectroscopy (MRS) of the brain, and genetic analysis have been performed in all six members of the family with the three patients with MNGIE. Two of them are monozygous twins. They all suffered from gastrointestinal dysmotility, cachexia, ophthalmoplegia, muscular atrophies, and polyneuropathy. Urinary thymidine was elevated in the patients related to the severity of clinical disease, and urinary thymidine (normally not detectable) was also found in a heterozygous carrier. Brain MRI showed leukoencephalopathy in all patients; however, their cognitive functioning was normal. Brain MRS demonstrated reduced N-acetylaspartate and choline in severely affected areas. MRI of heterozygous carriers was normal. A new mutation (T92N) in the TP gene was identified. Urinary thymidine is for the first time reported to be detectable in a heterozygous carrier. MRS findings indicate loss of neurons, axons, and glial cells in patients with MNGIE, but not in heterozygous carriers.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::621d3faf22f8d20aee3d80c953f72997Test
http://doc.rero.ch/record/318521/files/415_2006_Article_255.pdfTest

المؤلفون: Jean-Marc Burgunder, M. Weber, Th Lauterburg, Irene Tobler

المصدر: Neuroscience Letters. 358:17-20

مصطلحات موضوعية: medicine.medical_specialty, Substantia nigra, Dynorphin, Motor Activity, Biology, Rats, Sprague-Dawley, Dopamine receptor D1, Dopamine, Dopamine receptor D2, Internal medicine, medicine, Animals, Neurotransmitter Agents, Tyrosine hydroxylase, General Neuroscience, Dopaminergic, Brain, Circadian Rhythm, Rats, Receptors, Neurotransmitter, Ventral tegmental area, Endocrinology, medicine.anatomical_structure, Gene Expression Regulation, Neuroscience, medicine.drug

الوصف: Mammalian motor activity displays circadian patterns in normal behaviour and in many movement disorders, like levodopa responsive dystonia and Parkinson's disease. Here, we hypothesized that a circadian pattern of dopamine synthesis would trigger rhythms in the expression of genes in regions receiving dopaminergic innervation. Indeed tyrosine hydroxylase and cholecystokinin mRNA were upregulated in the substantia nigra and ventral tegmental area in the course of the day. However, in the caudate putamen, the mRNA levels, for dopamine D2 and adenosine 2A receptor, dynorphin, and substance P were lower during the day than during the night, whereas the expression of dopamine D1 receptor, enkephalin, and somatostatin was stable. In the frontal cortex, a clear midday peak of enkephalin expression was detected, while cholecystokinin and vasoactive intestinal peptide expression did not vary. Clear circadian gene expression patterns can therefore be demonstrated in brain regions involved in motor regulation, but they do not follow a simple dopaminergic drive and more complex regulatory patterns have to be assumed.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::10fdecc9b1ec678973c8488de23457cdTest
https://doi.org/10.1016/j.neulet.2003.12.053Test

المؤلفون: Li-Yen Lee, Akhlaq A. Farooqui, Gavin S. Dawe, Wei-Yi Ong, Jean-Marc Burgunder

المصدر: Neuroscience Letters. 453:6-8

مصطلحات موضوعية: Male, Reflex, Startle, medicine.medical_specialty, Phospholipase A2 Inhibitors, Striatum, Phospholipase A2, Internal medicine, Moro reflex, medicine, Animals, Enzyme Inhibitors, Rats, Wistar, Prepulse inhibition, Analysis of Variance, Phospholipase A, biology, Chemistry, General Neuroscience, Oligonucleotides, Antisense, Startle reaction, Rats, Phospholipases A2, Endocrinology, Acoustic Stimulation, Quinacrine, Acoustic Startle Reflex, Phospholipases A2, Calcium-Independent, Reflex, biology.protein, Neuroscience

الوصف: High levels of calcium-independent phospholipase A(2) (iPLA(2)) are present in the striatum and cerebral cortex [W.Y. Ong, J.F. Yeo, S.F. Ling, A.A. Farooqui, Distribution of calcium-independent phospholipase A(2) (iPLA(2)) in monkey brain, J. Neurocytol. 34 (2005) 447-458], and several clinical investigations have suggested a possible role of altered iPLA(2) activity in neurodegenerative and psychiatric disorders. The present study was carried out to elucidate a possible effect of PLA(2) on prepulse inhibition (PPI) of the acoustic startle reflex. Rats that received intraperitoneal injection of the non-specific PLA(2) inhibitor, quinacrine, showed significantly decreased PPI at 76, 80, and 84dB, compared to saline injected controls. In addition, rats that received intrastriatal injection of antisense oligonucleotide to iPLA(2) showed significant reduction in PPI at prepulse intensities of 76 and 84dB compared to scrambled sense injected controls. Together, these findings point to a role of PLA(2) in PPI of the auditory startle reflex and sensorimotor gating.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::dd83756bcd4d5c25bafaaa498dab49c8Test
https://doi.org/10.1016/j.neulet.2009.01.069Test

المؤلفون: Jean-Marc Burgunder, A. Richter, W. Löscher

المصدر: Experimental Brain Research. 129:114-120

مصطلحات موضوعية: Central Nervous System, medicine.medical_specialty, Tyrosine 3-Monooxygenase, Glutamate decarboxylase, Gene Expression, Hamster, Substantia nigra, Striatum, Biology, GAP-43 Protein, Cricetinae, Internal medicine, Basal ganglia, medicine, Animals, RNA, Messenger, Thyrotropin-Releasing Hormone, Mesocricetus, Tyrosine hydroxylase, Glutamate Decarboxylase, General Neuroscience, Hormones, Enzymes, Dystonia, Endocrinology, Cholecystokinin, Somatostatin, Pars reticulata, Golden hamster

الوصف: In the dt(sz) mutant hamster with idiopathic generalized dystonia, functional abnormalities of several neurotransmitters have been suggested to play a role in the development of symptoms. In the present study, we have used histochemistry with (35)S-ATP labeled oligonucleotides to determine whether these abnormalities are associated with modulation in the expression of neurotransmitter genes in motor regions. We examined the expression of genes encoding cholecystokinin (CCK), somatostatin (SRIF), thyrotropin-releasing hormone (TRH), glutamic acid decarboxylase (GAD), tyrosine hydroxylase (TH) and growth-associated protein 43 (GAP43) in the cortex and basal ganglia of dystonic hamsters and of non-dystonic control hamsters of a related inbred line and of a non-related outbred line. The distribution of these mRNAs in normal hamster brain was similar to that in normal rat brain. In all cortical regions studied (frontal, parietal and piriformis), the expression of CCK was similar in dystonic and inbred controls but was significantly greater than in outbred controls. In the anterior thalamus, CCK expression was lower in dystonic hamsters than in both control groups. SRIF expression was significantly decreased in the cortex and striatum of dystonic animals than in inbred and outbred control hamsters. GAD expression was lower in the striatum and substantia nigra, pars reticulata of dystonic than in outbred hamsters, but similar values were found in all groups in the other regions studied. TH was lower in the substantia nigra of dystonic than in inbred controls. No changes were found in GAP43 expression. This study demonstrates that changes in modulation of the expression of some peptides and neurotransmitter enzymes can be found in the dystonic hamster, which is in contrast to other animal models such as the dystonic rat, where no such changes have been found. The present data are consistent with previous findings in dt(sz) hamsters that suggest a dysfunction within the basal ganglia-thalamocortical circuits.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::cb3cab505da4ab93092f15ed9f0f75eaTest
https://doi.org/10.1007/s002210050941Test

المؤلفون: Gian Paolo Ramelli, Joachim Weis, Sabina Gallati, Jean-Marc Burgunder, Stephan Krähenbühl

المصدر: Journal of Child Neurology. 21:253-255

مصطلحات موضوعية: Genetics, medicine.medical_specialty, Ataxia, Muscular hypotonia, Hearing loss, Point mutation, Respiratory chain complex, Biology, medicine.disease, Short stature, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, 030225 pediatrics, Internal medicine, Diabetes mellitus, Pediatrics, Perinatology and Child Health, medicine, Sensorineural hearing loss, Neurology (clinical), medicine.symptom, 030217 neurology & neurosurgery

الوصف: We report on a family with a 12-year-old boy who suffered from a maternally inherited syndrome characterized by a combination of sensorineural hearing loss, myoclonus epilepsy, ataxia, severe psychomotor retardation, short stature, and diabetes mellitus. First, he showed a muscular hypotonia with hearing loss; later, he developed a myoclonus epilepsy, growth failure, and severe psychomotor retardation. At the age of 10 years, he developed diabetes mellitus. After initiation of combined ubiquinone and vitamin C treatment, we observed a progression in psychomotor development. Lactate and pyruvate levels in blood and cerebrospinal fluid were normal. No ragged red fibers or ultrastructural abnormalities were seen in a skeletal muscle biopsy. Biochemical assays of respiratory chain complex activities revealed decreased activity of complexes I and IV. By sequence analysis of mitochondrial DNA encoding transfer ribonucleic acids (RNAs), a homoplasmic T to C substitution at nucleotide position 7512 was found affecting a highly conserved base pair in the tRNAser(UCN) acceptor stem. Asymptomatic family members of the maternal line were heteroplasmic for the mutation in blood samples. Analysis of mitochondrial DNA in patients with hearing loss and myoclonus epilepsy is recommended, even in the absence of laboratory findings. Therapeutically, ubiquinone and antioxidants can be beneficial. ( J Child Neurol 2006;21:253—255; DOI 10.2310/7010.2006.00047).

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::9b44ba3cfb4bba5311348c149659ee76Test
https://doi.org/10.2310/7010.2006.00047Test

المؤلفون: Jean-Marc Burgunder

المصدر: Developmental Brain Research. 78:109-122

مصطلحات موضوعية: medicine.medical_specialty, Central nervous system, Gene Expression, In situ hybridization, Biology, Rats, Sprague-Dawley, Diencephalon, Prosencephalon, Developmental Neuroscience, Pregnancy, Internal medicine, medicine, Animals, RNA, Messenger, In Situ Hybridization, Cerebral Cortex, Neocortex, Histocytochemistry, Cerebrum, Allocortex, Rats, medicine.anatomical_structure, Endocrinology, Somatostatin, nervous system, Forebrain, Autoradiography, Female, Oligonucleotide Probes, Developmental Biology

الوصف: With hybridization histochemistry, somatostatin (SRIF) mRNA was detected in several neuronal populations of the basal diencephalon (anterior and posterior) and basal telencephalon (lateral) for the first time on the 14th day of gestation (E14). On E16, a large increase of the extent of expression was found in these populations. In addition, cells in the medial telencephalon and a few cells in the future allocortex also contained SRIF mRNA for the first time. In the prenatal period, the expression in the above populations continued to mature and individual nuclei with SRIF mRNA began to be recognizable. At birth, the overall pattern of SRIF gene expression was established but the ventral portions (hypothalamus, amygdala, allocortical areas) had higher levels of expression than the more dorsal ones (striatum and neocortex). Over the first 2 wk of life, this difference decreased and an adult-like pattern was found at postnatal day 21. We demonstrate that most of SRIF gene expression development takes place before birth. This description may serve as a basis for studies on the putative functions of SRIF during brain ontogeny.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a09f36cdc84ca10e81fc95fc726903e3Test
https://doi.org/10.1016/0165-3806Test(94)90015-9

المؤلفون: Kai M. Rösler, Séverine Petitprez, Lie Chen, Liliane Kappeler, D Schorderet, Hugues Abriel, Jean-Marc Burgunder, L Tiab

المصدر: Neurology. 71(21)

مصطلحات موضوعية: medicine.medical_specialty, Nav1.4, DNA Mutational Analysis, Transfection, Sodium Channels, Cell Line, Membrane Potentials, Myotonia, Internal medicine, medicine, Humans, Hyperkalemic periodic paralysis, Patch clamp, Isoleucine, NAV1.4 Voltage-Gated Sodium Channel, Membrane potential, Family Health, biology, Sodium channel, Valine, medicine.disease, Cell biology, Transmembrane domain, Protein Subunits, Endocrinology, Paramyotonia congenita, Mutation, biology.protein, Female, Neurology (clinical)

الوصف: Background: Mutations in SCN4A may lead to myotonia. Methods: Presentation of a large family with myotonia, including molecular studies and patch clamp experiments using human embryonic kidney 293 cells expressing wild-type and mutated channels. Results: In a large family with historic data on seven generations and a clear phenotype, including myotonia at movement onset, with worsening by cold temperature, pregnancy, mental stress, and especially after rest after intense physical activity, but without weakness, the phenotype was linked with the muscle sodium channel gene ( SCN4A ) locus, in which a novel p.I141V mutation was found. This modification is located within the first transmembrane segment of domain I of the Na v 1.4 α subunit, a region where no mutation has been reported so far. Patch clamp experiments revealed a mutation-induced hyperpolarizing shift (−12.9 mV) of the voltage dependence of activation, leading to a significant increase (approximately twofold) of the window current amplitude. In addition, the mutation shifted the voltage dependence of slow inactivation by −8.7 mV and accelerated the entry to this state. Conclusions: We propose that the gain-of-function alteration in activation leads to the observed myotonic phenotype, whereas the enhanced slow inactivation may prevent depolarization-induced paralysis.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::677b1aeb0f489949f8a9ef705e45ab19Test
https://pubmed.ncbi.nlm.nih.gov/19015483Test

المؤلفون: W. Scott Young, Jean-Marc Burgunder

المصدر: Developmental Brain Research. 52:85-93

مصطلحات موضوعية: medicine.medical_specialty, Tyrosine 3-Monooxygenase, Ontogeny, Substantia nigra, Biology, Midbrain, Embryonic and Fetal Development, Developmental Neuroscience, Mesencephalon, Dopamine, Internal medicine, medicine, Animals, RNA, Messenger, Gene, Tyrosine hydroxylase, Nucleic Acid Hybridization, Rats, Inbred Strains, Molecular biology, Rats, Ventral tegmental area, Endocrinology, medicine.anatomical_structure, Gene Expression Regulation, nervous system, Immunohistochemistry, Cholecystokinin, Developmental Biology, medicine.drug

الوصف: The ontogeny of tyrosine hydroxylase and cholecystokinin gene expression was studied in the rat mesencephalon using hybridization histochemistry. Both transcripts appeared on E13 in the ventrocaudal mesencephalon. The levels of both transcripts increased synchronously during the second half of gestation. The locations of neurons containing either transcript changed similarly during development with a rostral transposition and a lateral extension of the respective areas covered with grains. On the day after birth, the patterns of expression for both genes, although at lower transcript levels, were similar to the patterns seen in the adult.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::856f9c892b12f1afea714f261e94d40fTest
https://doi.org/10.1016/0165-3806Test(90)90224-m

المؤلفون: Benjamin K.C. Ong, Raymond C.S. Seet, Roland Baur, Chew Soh Eng, Shang Huifang, Erle C.H. Lim, Walter Hunziker, Pascal Béguin, Erwin Sigel, Jean-Marc Burgunder

المصدر: Neuromuscular disorders : NMD. 18(8)

مصطلحات موضوعية: musculoskeletal diseases, Male, congenital, hereditary, and neonatal diseases and abnormalities, medicine.medical_specialty, China, DNA, Complementary, Adolescent, Xenopus, Pain, Biology, Compound heterozygosity, medicine.disease_cause, Myotonia, Variable features, Chloride Channels, Internal medicine, medicine, Animals, Humans, Muscle, Skeletal, Exercise, Genetics (clinical), Genetics, Neurologic Examination, CLCN1, Mutation, Myotonia congenita, Electromyography, Reverse Transcriptase Polymerase Chain Reaction, medicine.disease, biology.organism_classification, Electrophysiology, Endocrinology, Neurology, Pediatrics, Perinatology and Child Health, Chloride channel, biology.protein, Oocytes, Female, Neurology (clinical)

الوصف: We describe two Chinese families with a mild form of the myotonia congenita due to novel chloride channel (ClCN1) mutations. In one case, heterozygous I553F and H555N mutations were found. The patient shared the I553F mutation with his healthy father, and his mother had a history of mild myotonia when she was younger. In another family, autosomal dominant myotonia congenita was due to a L844F change. The physiological effects of the mutations were examined by using the two-electrode voltage-clamp technique after expression of the channels in Xenopus oocytes. All mutations drastically shifted the voltage required for half-maximal activation, more under conditions mimicking the homozygous situation, than under conditions mimicking the heterozygous situation. The larger effect was seen in the compound heterozygous situation combining the I553F and the H555N mutations. Our data suggest that myotonia congenita caused by CLCN1 mutations in Chinese have similar variable features to those found in the West.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f0c2fdf4dfca35d7248e8e99f8ec0c33Test
https://pubmed.ncbi.nlm.nih.gov/18579381Test

المؤلفون: Li-Yen Lee, Akhlaq A. Farooqui, Wei-Yi Ong, Jean-Marc Burgunder

المصدر: Lee, Li-Yen; Ong, Wei-Yi; Farooqui, Akhlaq A; Burgunder, Jean-Marc (2007). Role of calcium-independent phospholipase A2 in cortex striatum thalamus cortex circuitry-enzyme inhibition causes vacuous chewing movements in rats. Psychopharmacology, 195(3), pp. 387-95. Berlin: Springer 10.1007/s00213-007-0912-y <http://dx.doi.org/10.1007/s00213-007-0912-yTest>

مصطلحات موضوعية: Male, medicine.medical_specialty, Cerebellum, Phosphodiesterase Inhibitors, Central nervous system, Thalamus, Organophosphonates, chemistry.chemical_element, Striatum, Arachidonic Acids, Biology, Calcium, Naphthalenes, Dopamine Uptake Inhibitors, Internal medicine, Cortex (anatomy), Basal ganglia, medicine, Animals, Enzyme Inhibitors, Rats, Wistar, Pharmacology, Benztropine, Cerebral Cortex, Behavior, Animal, Drug Administration Routes, Oligonucleotides, Antisense, Corpus Striatum, Rats, medicine.anatomical_structure, Endocrinology, nervous system, chemistry, Cerebral cortex, Organ Specificity, Pyrones, Phospholipases A2, Calcium-Independent, Stereotyped Behavior, Neuroscience

الوصف: RATIONALE: High levels of calcium independent phospholipase A2 (iPLA2) are present in certain regions of the brain, including the cerebral cortex, striatum, and cerebellum (Ong et al. 2005). OBJECTIVES: The present study was carried out to elucidate a possible role of the enzyme in the motor system. METHODS: The selective iPLA2 inhibitor bromoenol lactone (BEL), the nonselective PLA2 inhibitor methyl arachidonyl fluorophosphonate (MAFP), and an antisense oligonucleotide were used to interfere with iPLA2 activity in various components of the motor system. Control animals received injections of carrier (phosphate buffered saline, PBS) at the same locations. The number of vacuous chewing movements (VCM) was counted from 1 to 14 days after injection. RESULTS: Rats that received BEL and high-dose MAFP injections in the striatum, thalamus, and motor cortex, but not the cerebellum, showed significant increase in VCM, compared to those injected with PBS at these locations. BEL-induced VCM were blocked by intramuscular injections of the anticholinergic drug, benztropine. Increased VCM was also observed after intrastriatal injection of antisense oligonucleotide to iPLA2. The latter caused a decrease in striatal iPLA2 levels, confirming a role of decreased enzyme activity in the appearance of VCM. CONCLUSIONS: These results suggest an important role for iPLA2 in the cortex-striatum-thalamus-cortex circuitry. It is postulated that VCM induced by iPLA2 inhibition may be a model of human parkinsonian tremor.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::25babd4f6fd63dcb641e59b2d1647178Test
https://pubmed.ncbi.nlm.nih.gov/17768607Test