Noise of the slowly inactivating Na current in suprachiasmatic nucleus neurons

Slow depolarization induces a riluzole-sensitive persistent Na current (INa,P) in several types of neurons and a pharmacologically similar slowly inactivating Na current (INa,S) in rat suprachiasmatic nucleus neurons. In isolated suprachiasmatic nucleus neurons, INa,S fluctuations were analyzed to characterize the Na channel responsible for INa,S. The single-channel current near resting potential was -0.53+/-0.04 pA in an external solution containing 151 mM Na+ and 5 mM Na+ in the patch pipette. Tetrodotoxin completely blocked INa,S and single-channel current noise; 25 microM riluzole also suppressed INa,S and current noise by about 80% without a significant effect on mean single-channel current. The data suggest that single-channel noise is due to the opening of channels mediating INa,S with a conductance of about 3.4 pS.     

GGA proteins regulate retrograde transport of BACE1 from endosomes to the trans-Golgi network

Golgi-localized, gamma ear-containing, ADP ribosylation factor-binding (GGA) proteins have been shown to be implicated in the sorting of cargo proteins from the trans-Golgi network (TGN) to endosomal compartments. GGAs directly bind to DXXLL motifs in the cytoplasmic domains of cargo proteins. The Alzheimer-associated beta-secretase BACE1 also interacts with GGA proteins, but the functional relevance of this interaction was unknown. Here, we show that GGA1 regulates the retrograde transport of internalized BACE1 from endosomal compartments to the TGN by direct interaction in a phosphorylation-dependent manner. While phosphorylated BACE1 is efficiently transported from endosomes to the TGN, non-phosphorylated BACE1 enters a direct recycling route to the cell surface. Our data indicate that GGA proteins are not only involved in the sorting at the TGN but also mediate the retrograde transport of cargo proteins from endosomes to the TGN.     

Predisposing conditions and risk factors for development of symptomatic meningioma in adults

BACKGROUND: Risk factors and predisposing factors for the development of symptomatic meningioma during adult life are not well known. METHODS: Data from 306 consecutive patients with primary meningioma were collected retrospectively in a hypothesis-generating study. Factors studied included localisation of tumours, blood group typing, and risk factors, such as diabetes mellitus, coronary arterial disease, hypertension, rheumatoid arthritis, bronchial asthma, smoking, obesity, and second primary tumour. Case-control analysis of putative risk factors was carried out using a control data set from the German East-West Health Survey (n=7466, age range 25-69 years). Patients and controls were matched for age, gender, geographic area, and time of data collection. RESULTS: Rh(D) positive cases were significantly less frequent in the patient group compared to controls (p=0.01). Pre-existing diabetes was associated with meningioma in middle-aged (40-69 years) patients (odds ratio, OR 13.94-4.30, p=0.001-0.05). In female patients, arterial hypertension was significantly associated with occurrence of meningioma in the age group 60-69 years (OR=2.23, p=0.041). Rheumatoid arthritis had a negative association with meningioma in both males and females in the age groups above 50 years (OR 0.19-0.27, p=0.02-0.034). Bronchial asthma, smoking, and obesity were not significantly associated with meningioma. A second primary tumour was present in 12 cases. The most frequent combination was meningioma and breast cancer (5/12). CONCLUSIONS: This study shows statistically significant association of some co-morbidities with symptomatic meningioma in adults. Areas of interest have been identified where further research would be necessary.     

Patterns of developmental mRNA expression of neurturin and GFRalpha2 in the rat striatum and substantia nigra do not suggest a role in the regulation of natural cell death in dopamine neurons

We examined the mRNA expression of neurturin (NTN) and its receptor GFRalpha2 in rat substantia nigra (SN) and striatum by northern analysis at ages ranging from postnatal day (PND) 2 to adult. NTN mRNA expression is developmentally regulated in striatum with a peak at PND10, but its expression in striatum is low, and less than that of SN. In SN, there is no developmental regulation. GFRalpha2 was expressed most highly during the first two postnatal weeks. Like NTN, GFRalpha2 mRNA was also more abundant in SN, at both PND2 and 14. Our results show that NTN expression is relatively low in the striatum, the target of dopamine (DA) neurons, and there is no apparent pattern of developmental regulation in SN. Thus these studies are not strongly supportive of a role for NTN in regulating natural cell death (NCD) in DA neurons, either as a target-derived or as a local paracrine factor.     

Timed hypocaloric food restriction alters the synthesis and expression of vasopressin and vasoactive intestinal peptide in the suprachiasmatic nucleus

In mammals, the main circadian pacemaker is located in the suprachiasmatic nucleus (SCN) and its most potent synchronizer is the daily variation of the intensity of light. However, other nonphotic cues, such as timed food restriction, can induce changes in the circadian rhythms, leading also to the appearance of a food-entrained oscillator. The present study was designed to establish if the alterations of the circadian rhythms induced by timed hypocaloric food restriction are accompanied by structural changes in the SCN. Two groups of adult rats, both maintained on 12-h light/12-h dark cycles, were used; in one group, animals had permanent free access to food, whereas in the other they were subjected to a restricted hypocaloric early morning feeding during 7 months. Using stereological techniques and in situ hybridization, we have examined the structure of the SCN and the synthesis and expression of vasopressin (AVP) and vasoactive intestinal peptide (VIP). The volume of the SCN and the total number of neurons did not vary between the two groups. However, the total number of AVP- and VIP-immunoreactive neurons and the AVP and VIP mRNA levels were significantly decreased in timed hypocaloric food-restricted animals. The results indicate that timed hypocaloric food restriction has led to changes of AVP and VIP content of the neurons. They furthermore suggest the existence of a coupling between the food-entrainable oscillator and the light-entrainable pacemaker.     

Tick inoculation in an eyelid region: report on five cases with one complication of the orbital myositis associated with Lyme borreliosis

PURPOSE: To determine the frequency and dependence of Lyme borreliosis after tick infestation in the eyelid region. MATERIAL AND METHODS: Five patients after tick inoculation were investigated by immunofluorescence assays for IgM and IgG system). Ophthalmologic evaluation of myositis was supported with MRI, laboratory, and internal clinical investigations. RESULTS: Four children showed negative Borrelia serology after a bite from a tick. In one case the left abducens nerve palsy was found, which was diagnosed in MRI as a thickened left lateral rectus muscle. The diagnosis of myositis with positive Borrelia burgdorferi serology was consistent with Lyme borreliosis. Other laboratory examinations were negative. The symptoms were reduced after treatment with ceftriaxon. CONCLUSIONS: Lyme borreliosis was found in one in five patients after tick infestation in the eyelid region. Antibiotic prophylaxis against Lyme borreliosis with ampicillin is recommended for children after a tick bite.