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Molecular Neurodegeneration Jun 2011Prion diseases such as bovine spongiform encephalopathies (BSE) are transmissible neurodegenerative diseases which are presumably caused by an infectious conformational...
BACKGROUND
Prion diseases such as bovine spongiform encephalopathies (BSE) are transmissible neurodegenerative diseases which are presumably caused by an infectious conformational isoform of the cellular prion protein. Previous work has provided evidence that in murine prion disease the endogenous retrovirus (ERV) expression is altered in the brain. To determine if prion-induced changes in ERV expression are a general phenomenon we used a non-human primate model for prion disease.
RESULTS
Cynomolgus macaques (Macaca fasicularis) were infected intracerebrally with BSE-positive brain stem material from cattle and allowed to develop prion disease. Brain tissue from the basis pontis and vermis cerebelli of the six animals and the same regions from four healthy controls were subjected to ERV expression profiling using a retrovirus-specific microarray and quantitative real-time PCR. We could show that Class I gammaretroviruses HERV-E4-1, ERV-9, and MacERV-4 increase expression in BSE-infected macaques. In a second approach, we analysed ERV-K-(HML-2) RNA and protein expression in extracts from the same cynomolgus macaques. Here we found a significant downregulation of both, the macaque ERV-K-(HML-2) Gag protein and RNA in the frontal/parietal cortex of BSE-infected macaques.
CONCLUSIONS
We provide evidence that dysregulation of ERVs in response to BSE-infection can be detected on both, the RNA and the protein level. To our knowledge, this is the first report on the differential expression of ERV-derived structural proteins in prion disorders. Our findings suggest that endogenous retroviruses may induce or exacerbate the pathological consequences of prion-associated neurodegeneration.
PubMed: 21699683
DOI: 10.1186/1750-1326-6-44 -
Neuroscience 1999Recent electrophysiological observations suggest that, in addition to the medial septal area pacemaker system, several alternative or additional mechanisms are involved...
Recent electrophysiological observations suggest that, in addition to the medial septal area pacemaker system, several alternative or additional mechanisms are involved in the generation/regulation of hippocampal theta activity. Discharging neurons phase-locked to hippocampal theta waves have been observed in the dorsal raphe, nucleus reticularis pontis oralis and especially in the supramammillary region of rats. Since these areas are reciprocally interconnected with the hippocampal formation, including the entorhinal cortex, it would aid our understanding of limbic function to elucidate the location and neurochemical content of the entorhino-septal and septo-supramammillary projection neurons, as well as that of their postsynaptic targets. Light and electron microscopic immunostaining for calretinin, in combination with antero- and retrograde tracer techniques, postembedding immunostaining for GABA and the transmitter specific [3H]D-aspartate retrograde radiolabeling, as well as a co-localization experiment for calretinin and glutamate decarboxylase in rat supramammillary and septal neurons, demonstrated that: (i) a large population of entorhinal cells that forms asymmetric synaptic contacts on calretinin-containing neurons located at the border between the medial and lateral septal areas contains calretinin and are aspartate/glutamatergic; (ii) the overwhelming majority of calretinin-immunoreactive cells located at the border between the lateral and medial septal area are GABAergic; (iii) these neurons can be retrogradely labeled from the supramammillary area; (iv) anterogradely labeled axons originating in the border between the medial and lateral septum are GABAergic and (v) terminate on supramammillary area non-GABAergic, calretinin-containing neurons, which are known to project to the septal complex and hippocampus. These observations indicate that a large population of cells participating in the hippocampal feedback regulation of theta regulation/generation contain the same calcium-binding protein. Furthermore, entorhinal excitatory transmitter-containing neurons can depress the activity of supramammillary theta generating/regulating cells via septal inhibitory neurons.
Topics: Animals; Aspartic Acid; Axonal Transport; Calbindin 2; Entorhinal Cortex; Feedback; Female; Hippocampus; Male; Mammillary Bodies; Nerve Tissue Proteins; Neural Pathways; Neurons; Phytohemagglutinins; Rats; Rats, Sprague-Dawley; S100 Calcium Binding Protein G; Septal Nuclei; Theta Rhythm; gamma-Aminobutyric Acid
PubMed: 10363811
DOI: 10.1016/s0306-4522(98)00245-0 -
Journal of Neurological Surgery. Part... Apr 2024Emotional lability (EL), the uncontrollable and unmotivated expression of emotion, is a rare and distressing symptom of brainstem compression. In published case...
Emotional lability (EL), the uncontrollable and unmotivated expression of emotion, is a rare and distressing symptom of brainstem compression. In published case reports, EL from an extra-axial posterior fossa tumor was alleviated by tumor resection. The primary aim herein was to radiographically establish the degree of compression from mass lesions onto brainstem structures. Secondarily, we compared changes in patient-reported quality of life (QOL) pre- and postoperatively. A retrospective review of posterior fossa tumors treated between 2002 and 2018 at Vancouver General Hospital revealed 11 patients with confirmed EL. Each case was matched to three controls. A lateral brainstem compression scale characterized mass effect at the level of the medulla, pons, and midbrain in preoperative axial T2-weighted fluid-attenuated inversion recovery magnetic resonance imaging (FLAIR MRI) scans. Compression and clinical variables were compared between patient groups. Short Form-36 version 1 health surveys were retrospectively obtained from patient charts to compare pre- versus postoperative changes in survey scores between EL and control patients. EL symptoms ceased postoperatively for all EL patients. EL tumors exert greater compression onto the pons ( = 0.03) and EL patients more commonly have cerebellar findings preoperatively ( = 0.003). Patients with EL-causing tumors experienced greater improvement postoperatively in "Health Change" ( = 0.05), which was maintained over time. Findings suggest that compression onto the pons inhibits control over involuntary, stereotyped expression of emotion. This adds to evidence that EL may be attributed to cerebellum deafferentation from cortical and limbic structures through the basis pontis, leading to impaired modulation of emotional response. QOL results augment benefits of offering patients EL-alleviating tumor resection surgery.
PubMed: 38449579
DOI: 10.1055/a-2028-6373 -
Radiology Case Reports Aug 2023We reported a case of Wallerian degeneration of the unilateral middle cerebellar peduncle (MCP) that developed after ipsilateral paramedian lower pontine infarction. The...
We reported a case of Wallerian degeneration of the unilateral middle cerebellar peduncle (MCP) that developed after ipsilateral paramedian lower pontine infarction. The patient was a 70-year-old woman with right hemiparesis and dysarthria. Using a 3-Tesla scanner, cranial magnetic resonance imaging was performed, and an infarct was found at the left paramedian lower pons. Seven months later, an abnormal signal was found at the central portion of the left MCP, indicative of Wallerian degeneration of the pontocerebellar tract (PCT). There was no abnormality at the contralateral MCP. Usually, Wallerian degeneration of the bilateral MCPs may develop after unilateral paramedian pontine infarction, because bilateral PCTs cross each other at the midline of the basis pontis. In the present case, however, Wallerian degeneration was found at only the ipsilateral MCP. The contralateral PCT was not affected because the PCT runs in the craniocaudal direction, and our patient had a lower pontine infarct. The location of the pontine infarct (affected PCT) and the Wallerian degeneration of the side of the MCP were well correlated.
PubMed: 37388256
DOI: 10.1016/j.radcr.2023.05.033 -
AJNR. American Journal of Neuroradiology Mar 2007Morphometry and spectroscopy were performed in 3 patients with fragile X-associated tremor/ataxia syndrome (FXTAS). The brain stem and cerebellum were atrophic and...
Morphometry and spectroscopy were performed in 3 patients with fragile X-associated tremor/ataxia syndrome (FXTAS). The brain stem and cerebellum were atrophic and satisfied criteria for olivopontocerebellar atrophy in 2 patients. However, the vermis was relatively spared and the basis pontis maintained its oval shape. The only spectroscopic abnormality was a decrease of the pontine N-acetylaspartate/creatine ratio in 1 patient. Atrophy and metabolic changes in FXTAS differ to some extent from those of olivopontocerebellar atrophy.
Topics: Aged; Ataxia; Brain Stem; Cerebellum; Diagnosis, Differential; Fragile X Syndrome; Humans; Magnetic Resonance Spectroscopy; Male; Protons; Tremor
PubMed: 17353317
DOI: No ID Found -
Journal of Neurology, Neurosurgery, and... May 1986A family with recessively inherited ataxia and dystonic episodes that responded to antiepileptic medication is described. The onset was in the first decade. Clinically...
A family with recessively inherited ataxia and dystonic episodes that responded to antiepileptic medication is described. The onset was in the first decade. Clinically the patients have gait and limb ataxia, nystagmus and brisk reflexes, with abnormal visual, auditory and somatosensory evoked responses, but normal nerve conduction velocities and electromyography. Their intelligence is borderline. CT and MRI scans show severe atrophy in the vermis and basis pontis.
Topics: Adolescent; Adult; Ataxia; Brain; Dystonia; Electrodiagnosis; Female; Genes, Recessive; Humans; Magnetic Resonance Spectroscopy; Male; Nystagmus, Pathologic; Reflex, Abnormal; Tomography, X-Ray Computed
PubMed: 3711921
DOI: 10.1136/jnnp.49.5.591 -
Nihon Ronen Igakkai Zasshi. Japanese... Jul 1996The characteristics of multiple spongy necrosis of the basis pontis (MSN), central pontine myelinolysis (CPM), and cerebrovascular disease (CVD) of the pons developing...
The characteristics of multiple spongy necrosis of the basis pontis (MSN), central pontine myelinolysis (CPM), and cerebrovascular disease (CVD) of the pons developing in the elderly have not been fully clarified. We therefore studied 305 patients (aged 60-107, mean: 83.9) autopsied in Nagoya City Kohseiin Geriatric Hospital. MSN was found in four patients (1.3%). The major histologic finding was multiple necrosis of the basis pontis, characterized by loss of myelin and axons, no reactive astrocytes or inflammatory cells were found. Small foci of spongy necrosis appeared to unite with each other to form larger lesions. The central basis pontis was weakly stained by Klüver-Barrera stain in 15 patients, which suggested the presence of CPM. However, the diagnosis was only confirmed in one patient, (by the myelinolysis, loss of oligodendroglia, infiltration of macrophages, and reactive astrocytosis). With regard to CVD, none of the 305 patients had macroscopic pontine hemorrhage, but histologically small and old hemorrhagic lesions were found in 15. These lesions were associated with hypertensive or arteriosclerotic changes in the pontine vessels. Pontine infarction was evident in 77 patients (25.2%). In most lesions (74%) the area of infarction was smaller than 1 mm2. In 27 of the 74 patients with lacunar or microscopic infarcts, the pontine infarcts were found in areas where the blood was supplied through the short circumferential branch.
Topics: Age Factors; Aged; Aged, 80 and over; Cerebrovascular Disorders; Female; Humans; Male; Middle Aged; Myelinolysis, Central Pontine; Necrosis; Pons
PubMed: 8890607
DOI: 10.3143/geriatrics.33.524 -
The Journal of Neuroscience : the... Mar 1981Evidence that L-glutamate is a neurotransmitter of corticofugal fibers was sought by measuring changes in several biochemical markers of neurotransmitter function after...
Evidence that L-glutamate is a neurotransmitter of corticofugal fibers was sought by measuring changes in several biochemical markers of neurotransmitter function after pericruciate (sensorimotor) ablations in cats. Two weeks after cortical ablation, samples from various brain regions were analyzed for high affinity uptake of glutamate, gama-aminobutyric acid (GABA), glycine, alanine, and tyrosine. Amino acid levels and the activity of choline acetyltransferase (CAT) also were determined. High affinity glutamate uptake is decreased relative to the opposite side in areas of the nervous system which lost a predominantly unilateral corticofugal projection. These areas include the caudate nucleus, ventrolateral thalamic nucleus, red nucleus, basis pontis, and cervical and lumbar spinal cord. No significant changes were found in the uptake of other amino acids or in CAT in these regions. Changes in the levels of amino acids were significant only in ventrolateral thalamus where there was a 33% decrease in glutamate on the deafferented side. The data suggest that L-glutamate is a neurotransmitter of corticofugal fibers to many subcortical areas related to motor control.
Topics: Amino Acids; Animals; Biological Transport; Brain; Cats; Cerebral Cortex; Choline O-Acetyltransferase; Glutamates; Glutamic Acid; Histocytochemistry; Organ Specificity; Spinal Cord; gamma-Aminobutyric Acid
PubMed: 6114994
DOI: 10.1523/JNEUROSCI.01-03-00241.1981 -
The Journal of Biological Chemistry Mar 1999Three separate classes of ribonucleotide reductases are known, each with a distinct protein structure. One common feature of all enzymes is that a single protein...
Three separate classes of ribonucleotide reductases are known, each with a distinct protein structure. One common feature of all enzymes is that a single protein generates each of the four deoxyribonucleotides. Class I and III enzymes contain an allosteric substrate specificity site capable of binding effectors (ATP or various deoxyribonucleoside triphosphates) that direct enzyme specificity. Some (but not all) enzymes contain a second allosteric site that binds only ATP or dATP. Binding of dATP to this site inhibits the activity of these enzymes. X-ray crystallography has localized the two sites within the structure of the Escherichia coli class I enzyme and identified effector-binding amino acids. Here, we have studied the regulation of three class II enzymes, one from the archaebacterium Thermoplasma acidophilum and two from eubacteria (Lactobacillus leichmannii and Thermotoga maritima). Each enzyme has an allosteric site that binds ATP or various deoxyribonucleoside triphosphates and that regulates its substrate specificity according to the same rules as for class I and III enzymes. dATP does not inhibit enzyme activity, suggesting the absence of a second active allosteric site. For the L. leichmannii and T. maritima enzymes, binding experiments also indicate the presence of only one allosteric site. Their primary sequences suggest that these enzymes lack the structural requirements for a second site. In contrast, the T. acidophilum enzyme binds dATP at two separate sites, and its sequence contains putative effector-binding amino acids for a second site. The presence of a second site without apparent physiological function leads to the hypothesis that a functional site was present early during the evolution of ribonucleotide reductases, but that its function was lost from the T. acidophilum enzyme. The other two B12 enzymes lost not only the function, but also the structural basis for the site. Also a large subgroup (Ib) of class I enzymes, but none of the investigated class III enzymes, has lost this site. This is further indirect evidence that class II and I enzymes may have arisen by divergent evolution from class III enzymes.
Topics: Allosteric Regulation; Amino Acid Sequence; Biopolymers; Lactobacillus; Molecular Sequence Data; Oxidation-Reduction; Protein Binding; Ribonucleotide Reductases; Ribonucleotides; Sequence Homology, Amino Acid; Thermoplasma; Thermotoga maritima; Vitamin B 12
PubMed: 10066778
DOI: 10.1074/jbc.274.11.7182 -
The Pan African Medical Journal 2019Osmotic demyelination syndrome is characterized by the loss of myelin in the center of the basis pontis and other areas of the central nervous system. We report a case...
Osmotic demyelination syndrome is characterized by the loss of myelin in the center of the basis pontis and other areas of the central nervous system. We report a case of osmotic demyelination syndrome in a 55-year-old female, with a past medical history of arterial hypertension and multi-level cervical spondylosis, hospitalized for acute altered mental status complicating an array of acute gastroenteritis, the patient was afebrile. The course was marked by neurologic aggravation with confusion, aphasia, tetraplegia and osteo-tendinous areflexia. Initial cerebral magnetic resonance imaging did not show any specific abnormalities. The diagnosis of Central pontine myelinolysis and extrapontine myelinolysis was confirmed by a cerebral magnetic resonance imaging done after 20 days of the first. The rapid correction of hyponatremia was the main cause of this syndrome, without neglecting the very likely role of the associated hypokalemia. The evolution of centropontine myelinolysis (CPM) and extrapontine myelinolysis (EPM) is variable. The treatment is primarily preventive based on the careful correction of severe hyponatraemia and contributing factors.
Topics: Female; Humans; Hypokalemia; Hyponatremia; Magnetic Resonance Imaging; Middle Aged; Myelinolysis, Central Pontine; Syndrome
PubMed: 32180882
DOI: 10.11604/pamj.2019.34.208.19968