Neurofilament heavy-chain NfH(SMI35) in cerebrospinal fluid supports the differential diagnosis of Parkinsonian syndromes.

We aimed to evaluate the potential of the cerebrospinal fluid (CSF) axonal damage biomarker NfH(SMI35) in the laboratory-supported differential diagnosis of parkinsonian syndromes. Patients with idiopathic Parkinson's disease (PD; n = 22), multiple-system atrophy (MSA; n = 21), progressive supranuclear palsy (PSP; n = 21), corticobasal degeneration (CBD; n = 6), and age-matched controls (n = 45) were included. CSF levels of NfH(SMI35) were measured using ELISA. Levels of CSF NfH(SMI35) were elevated in PSP compared to PD and controls (P < 0.05 each). They were also significantly higher in MSA than in PD and controls (P < 0.05 each). NfH(SMI35) differentiated PD from PSP with a sensitivity of 76.5% and a specificity of 94.4%. Axonal damage as measured by CSF NfH(SMI35) is most prominent in the more rapidly progressive syndromes PSP and MSA as compared to PD or CBD. CSF NfH(SMI35) may therefore be of some value for the laboratory-supported differential diagnosis of atypical parkinsonian syndromes.     

Lindane inhibition of [35S]TBPS binding to the GABAA receptor in rat brain.

The inhibition of [³⁵S]t-butylbicyclophosphorothionate ([³⁵S]TBPS) binding to the GABA_A receptor by the insecticide γ-hexachlorocyclohexane, lindane, was studied in several brain regions and using different membrane preparation methods, both in vitro and after dosing the animals with the chemical. In the latter studies, the amount of lindane remaining in the membrane suspensions used for binding assays was determined. In vitro data showed values of IC₅₀ from 150 to 1675 nM, varying in function of the membrane preparation method used. This may account for the discrepancies in IC₅₀ values found in the literature. IC₅₀ values within the range of 150–250 nM were determined using extensively washed membranes from several brain regions, so no evidence arose for brain regional differences in the affinity of lindane for the TBPS binding site. After different schedules of acute treatment with lindane, we found a manifest relationship between the extent of the observable inhibition of [³⁵S]TBPS binding and the lindane amount remaining in the membrane suspensions used for binding assays. This relationship was in good agreement with the in vitro data, so no support for an in vivo acute regulation of the binding site was obtained.     

Morphological characteristics and immunohistochemical detection of nicotinic acetylcholine receptors on intestinofugal afferent neurones in guinea-pig colon

Intestinofugal afferent neurones (IFANs) provide excitatory synaptic input to abdominal prevertebral ganglion neurones. Input is greatly reduced during blockade of nicotinic acetylcholine receptors (nAChRs) in the wall of the colon, suggesting two projection pathways: a direct pathway without synaptic interruption and an indirect pathway interrupted by at least one nicotinic cholinergic synapse. This study aimed to characterize the morphology of IFANs and examine the distribution of nAChRs on them. We identified IFANs in guinea-pig colon by retrograde labelling with fluorescent tracer DiI placed either on the lumbar colonic nerves in vitro or inferior mesenteric ganglion in vivo. Confocal laser scanning microscopy and computerized image-processing software were used for 3D image reconstruction. Approximately 70% of identified IFANs had Dogiel type I-like morphology, the remainder were Dogiel type II-like. In vivo labelled IFANs were injected with Lucifer Yellow and immunostained for nAChRs using monoclonal antibody MAb35. Approximately 3% of total plasma membrane surface of IFANs with Dogiel type I morphology had MAb35-IR. In contrast, <1% of membrane surface of IFANs with Dogiel type II morphology had MAb35-IR. The finding that IFANs displayed immunostaining for nAChRs suggests the presence of putative nicotinic synapses.     

Dimebon and Tacrine Inhibit Neurotoxic Action of β-Amyloid in Culture and Block L-type Ca2+ Channels

Dimebon, a Russian-made drug, inhibited toxic effects of beta -amyloid on cultured neurons. Excessive accumulation of beta-amyloid in the brain is characteristic of Alzheimer dementias. Antialzheimer preparations tacrine and dimebon improve survival of cerebellar granule cells during long-term incubation with Ab25-35, the neurotoxic fragment of beta-amyloid. Both preparations can block potential-dependent Ca²⁺ entry into neurons by about 20%, which is explained by their selective action on L-type Ca²⁺ channels. It was assumed that the neuroprotective effect of dimebon and tacrine against Ab25-35 partially depends on inhibition of potential-dependent Ca²⁺ entry.     

HnRNP CBP35-CBP67 interaction during stress response and ageing

Previous studies have demonstrated the existence of nuclear carbohydrate binding proteins in a variety of mammalian cells with molecular masses of 35 000, 67 000, and 70 000 (CBP35, CBP67, and CBP70), which are associated with nuclear ribonucleoprotein (RNP) complexes. CBP35 consists of two domains, an aminoterminal portion that is homologous to certain regions of proteins of the heterogeneous nuclear RNP complex, and a carboxyl-terminal portion homologous to β-galactoside-specific lectins. CBP35 it has been proposed, like the glucose-specific lectin, CBP67, to guide RNP complexes through the nuclear pore. Here we show that the exposure of mature rats to stress induces an increase in nuclear CBP35 bound to CBP67 and retained on immobilized glucose. Nuclear extracts from the livers of old rats displayed no detectable stress response. This CBP35·CBP67 association detected in rat liver is considered with respect to the CBP35·CBP70 association recently observed in HL60 cell nuclear extracts.     

IL-12家族新成员及其在免疫应答中的重要调节作用

白细胞介素-12(Interleukin-12, IL-12)家族成员IL-12、 IL-23、 IL-27三者及其各自受体在结构上的相似性, 使得它们在发挥调节NK细胞活性、 T细胞增殖和细胞因子产生以及抗体类别转换等方面的功能相互重叠但又不完全相同.而2007年发现的该家族的另一新成员IL-35, 结构上虽与其他3个成员同源, 但却具有独特的生物学功能, 是一种主要由调节性T细胞(Treg)分泌的抑制性细胞因子.IL-12家族各成员以及同其他细胞因子之间存在着相互协同、相互拮抗的网络, 不仅在细胞内感染及炎症过程中起着重要的调节作用, 而且与银屑病、多发性硬化症、 Crohn' s病等多种临床疾病的发病密切相关.IL-12家族相关生物制品在自身免疫性疾病、感染性疾病以及肿瘤的治疗中有着广阔的应用前景.     

Specific activation of the mu opioid receptor (MOR) by endomorphin 1 and endomorphin 2

The recently discovered endomorphin 1 (Tyr-Pro-Trp-Phe-NH2) and endomorphin 2 (Tyr-Pro-Phe-Phe-NH2) were investigated with respect to their direct receptor-binding properties, and to their ability to activate G proteins and to inhibit adenylyl cyclase in both cellular and animal models. Both tetrapeptides activated G proteins and inhibited adenylyl cyclase activity in membrane preparations from cells stably expressing the mu opioid receptor, an effect reversed by the mu receptor antagonist CTAP (D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2), but they had no influence on cells stably expressing the delta opioid receptor. To further establish the selectivity of these peptides for the mu opioid receptor, brain preparations of mice lacking the mu opioid receptor gene were used to study their binding and signalling properties. Endomorphin 2, tritiated by a dehalotritiation method resulting in a specific radioactivity of 1.98 TBq/mmol (53.4 Ci/mmol), labelled the brain membranes of wild-type mice with a Kd value of 1.77 nM and a Bmax of 63.33 fmol/mg protein. In membranes of mice lacking the mu receptor gene, no binding was observed, and both endomorphins failed to stimulate [35S]guanosine-5'-O-(3-thio)triphosphate ([35S]GTPgammaS) binding and to inhibit adenylyl cyclase. These data show that endomorphins are capable of activating G proteins and inhibiting adenylyl cyclase activity, and all these effects are mediated by the mu opioid receptors.