Proteomic characterisation of neuronal sphingolipid-cholesterol microdomains: role in plasminogen activation

Sorting of certain membrane proteins requires a mechanism involving rafts, protein-lipid complexes enriched in glycosphingolipids and cholesterol. These microdomains remain at the plasma membrane of different cell types and play a role in signal transduction. Although recent reports have begun to describe molecules associated with rafts, their protein composition remains largely unknown, especially in neuronal cells. To address this question, we have purified detergent-insoluble raft fractions (DRMs) from primary cultures of hippocampal neurons. Bidimensional gel analysis and pharmacological raft lipid manipulation allowed the identification of neuronal raft proteins and their characterisation by MALDI-TOF analysis. Enolases were found among the proteins identified and functional studies demonstrate their participation in plasminogen binding. We also show the specific enrichment in rafts of several other plasminogen binding molecules and the exclusive activation of plasminogen to the protease plasmin in these microdomains. These observations suggest that neuronal rafts may play, in addition to intracellular signaling, a role in extracellular/membrane protein proteolysis.     

Gender differences in coping with tension-type headaches

OBJECTIVE: To study gender differences of coping with illness strategies in tension-type headaches. METHOD: We enrolled 89 subjects (50 women, 39 men) suffering from episodic (n = 37) and chronic (n = 52) tension-type headaches (TTH). Patients were required to answer a Freiburg Questionnaire of Coping with Illness (FQCI), a Von Zerssen Depression Scale (D-S), quality-of-life questionnaires, and a headache home diary (over 4 weeks). In addition, pressure pain thresholds (temporal muscles) and Total Tenderness Scores were obtained. RESULTS: While pain intensity, frequency and quality-of-life parameters were basically the same for female and male EPISODIC TTH sufferers, women scored significantly higher on the F3 subscale (distracting and encouraging) of the FQCI and tended to score higher on the F1 subscale (depressive). Among CHRONIC TTH patients, women reported the pain to be more intense (VAS), were more depressed (D-S), and scored lower on several quality-of-life scores. Female chronic TTH sufferers scored significantly lower on the F2 subscale (active coping) and tended to score higher on F5 (denying). CONCLUSIONS: We conclude that pessimistic coping with illness strategies are more frequent in female episodic and chronic TTH sufferers. We would like to recommend special psychologic intervention in particular to female chronic TTH sufferers which would offer counseling in developing active coping skills.     

Distribution of CNTF receptor alpha protein in the central nervous system of the chick embryo

Ciliary neurotrophic factor (CNTF) promotes the survival and differentiation of various neuronal and glial cell populations in the nervous system of vertebrates. In mammals, the ligand-binding alpha-subunit of the CNTF receptor (CNTFRalpha) is expressed in a variety of neuronal populations, including all CNTF-responsive cells. Previous studies suggested that functional differences in the CNTF/CNTF receptor system between chicks and mammals exist. The purpose of the present study was to examine the temporal and spatial expression pattern of the chick CNTFRalpha protein during CNS development. Receptor expression was detectable by immunoblotting in all CNS areas tested but showed area-specific developmental regulation. Interestingly, two variants of CNTFRalpha, 69 and 65 kD, were identified by immunoblotting with a shift from the higher to the lower molecular mass species occurring during development. Immunoreactivity for CNTFRalpha protein was preferentially observed in neuropil and white matter structures of the developing CNS while neuronal somata generally appeared unlabeled. For example, expression was observed in the olfactory system, in the telencephalon, in parts of the somatosensory system, in components of the tectofugal pathway, in the cerebellum, and in auditory brainstem nuclei. Fiber tracts that exhibit CNTFRalpha immunoreactivity were the lateral forebrain bundle, occipitomesencephalic tract, quintofrontal tract, and vestibular nerve. Our study identifies potential new targets of a chick CNTF-related molecule and reveals significant regional differences of CNTFRalpha protein expression between chick and mammals. These results suggest that the CNTF receptor performs distinct developmental functions in different animals.     

Dr. Elisabeth Hecker (1895-1986): career in child and adolescent psychiatry on the one hand--involvement in elimination of the handicapped on the other hand

During the period of national socialism in Loben/Lublinitz (Silesia) existed a children's special department, where many disabled and mentally retarded children were killed. This was happened under participation of the physician Elisabeth Hecker, who was one of the pioneer's of child and adolescent psychiatry in Germany. During the Second World War she was director of the Loben's clinic for adolescent psychiatry--one of the first of its sort and situated directly in the neighbourhood of the children's special department. Hecker announced children with negative ratings to the "Reich Committee for the Scientific Registration of Severe Genetically and Constitutionally Determined Diseases" in Berlin and transferred them to the children's special department in Loben. In 1979 the German Association of Child and Adolescent Psychiatry appointed Hecker as a honorary member for her commitment after the war. This honorary membership has been discussed critically because of her activities during the period of national socialism. The following paper analyses Hecker's involvement to the child "euthanasia" program based on unnoticed archival sources.