Glucocorticoids Decrease Hippocampal and Prefrontal Activation during Declarative Memory Retrieval in Young Men

Glucocorticoids (GCs, cortisol in human) are associated with impairments in declarative memory retrieval. Brain regions hypothesized to mediate these effects are the hippocampus and prefrontal cortex (PFC). Our aim was to use fMRI in localizing the effects of GCs during declarative memory retrieval. Therefore, we tested memory retrieval in 21 young healthy males in a randomized placebo-controlled crossover design. Participants encoded word lists containing neutral and emotional words 1 h prior to ingestion of 20 mg hydrocortisone. Memory retrieval was tested using an old/new recognition paradigm in a rapid event-related design. It was found that hydrocortisone decreased brain activity in both the hippocampus and PFC during successful retrieval of neutral words. These observations are consistent with previous animal and human studies suggesting that glucocorticoids modulate both hippocampal and prefrontal brain regions that are crucially involved in memory processing. Electronic Supplementary Material The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

照射与免疫的时间间隔对抗体形成的影响及其辐射剂量效应

本实验观察了0. 25、0. 5、1. 0、2. 0、3. 0和4. 0Gy全身照射后3至6 h羊红细胞(SRBC)免疫对小鼠脾脏抗体形成细胞(PFC)的影响。结果发现,各剂量照射后,免疫与照射的时间间隔较长者,辐射对PFC反应的抑制显著加深。照射后3及6h免疫,脾脏PFC反应均随照射剂量的增加而降低。照射后3h免疫时,PFC反应的D_(37)值为4. 13Gy;照射后6h免疫时,PFC反应的D_(37)值为1. 74Gy。     

The effect of phenytoin in vitro on normal human mononuclear cells and on human lymphoblastoid B cell lines of different Ig isotype specificities

The anticonvulsant drug phenytoin, in less than cytotoxic concentrations, caused significant reductions in Ig secretion by unstimulated or EBV-stimulated normal MNC, as measured by PFC or secretion of Ig into the culture medium. Isotype-specific LBL varied in their sensitivity, the secretion of IgA (1 line) and IgG (3 lines) being reduced by phenytoin near therapeutic concentrations, whereas that of IgM (1 line) was resistant. Six-day exposure of MNC to phenytoin caused no selective depletion of or enrichment for B cells, monocytes or T cell subsets. The results suggest that the reduction in serum Ig levels reported in phenytoin-treated epileptic patients is, at least in part, due to a direct effect of the drug on the B lymphocyte. However, among EBV-activated normal MNC, those secreting IgA were no more sensitive to the drug than those secreting IgG or IgM, and other factors may, therefore, operate to cause the preferential reduction in serum IgA in phenytoin-treated patients.     

Idiotypic characterization of antibody-induced antibody responses

Anti-idiotypic antisera were produced in syngeneic (C57BL/6) mice against a monoclonal anti-Dextran B512 (Dex) antibody (38-13). In radioimmunoassays, anti-idiotypic antibodies were shown to react with the homologous idiotype, while failing to recognize another monoclonal anti-Dex antibody, independently derived from C57BL/6 mice (D-16). Plaque inhibition tests confirmed the specificity of the anti-idiotypic antibodies and revealed that the 38-13 idiotype is expressed by about half of all anti-Dex antibodies produced in C57BL/6, but not in CBA mice. Injection of normal (but not athymic) C57BL/6 mice with low doses of 38-13 monoclonal antibodies, contained culture supernatants or ascitic fluids, resulted in a 10-20 fold increase in the numbers of anti-Dex PFC detected in the spleen 5 days later, the majority of which carried the 38-13 idiotype.     

Induction of immunoglobulin-producing human peripheral blood lymphocytes in serum-free medium

Induction of immunoglobulin-secreting cells from human peripheral blood lymphocytes in a serum-free culture medium was studied. Albumin, transferrin, insulin and fibronectin can replace serum entirely for support of pokeweed mitogen (PWM)-stimulated B lymphocytes, measured by a reverse hemolytic plaque assay using protein A-coated red cells. In this serum-free system, growth and maturation to IgM and IgG secretion occur at the same or higher efficiency as in conventional serum-containing medium, with maximum numbers of plaque-forming cells on day 6 at optimal dose of PWM, 0.5 ～ 5 μg/ml. This system can be used to avoid the interference from undefined serum components.     

苦丁茶对小鼠免疫功能的影响

目的：了解苦丁茶对小鼠免疫力功能的影响。方法：采用不同剂量的苦丁茶对小鼠进行体液免疫和细胞免疫功能测定。结果：若干 丁茶煎液具有增强小鼠腹腔Mφ的吞噬功能。提高脾细胞溶血空斑（PFC）数目。结论：苦丁茶有增强和高压 节机体免疫功能作用。     

鲨肝活性肽S-8300免疫调节作用的研究

研究鲨肝活性肽S-8300对免疫抑制小鼠的免疫调节作用。方法：观察鲨肝活性肽S-8300对环磷酰胺致免疫抑制小鼠血清溶血素、溶血空斑形成及血清IL-2含量的影响。结果：鲨肝活性肽S-8300可显著促进免疫抑制小鼠溶血素、溶血空斑形成及血清IL-2水平增高．结论：鲨肝活性肽S-8300对环磷酰胺致免疫抑制小鼠有较好的免疫调节作用。     

Alcohol exposure during development: Impact on the epigenome

Fetal alcohol spectrum disorders represent a wide range of symptoms associated with in utero alcohol exposure. Animal models of FASD have been useful in determining the specific neurological consequences of developmental alcohol exposure, but the mechanisms of those consequences are unclear. Long-lasting changes to the epigenome are proposed as a mechanism of alcohol-induced teratogenesis in the hippocampus. The current study utilized a three-trimester rodent model of FASD to examine changes to some of the enzymatic regulators of the epigenome in adolescence. Combined pre- and post-natal alcohol exposureresulted in a significant increase in DNA methyltransferase activity (DNMT), without affecting histone deacetylase activity (HDAC). Developmental alcohol exposure also caused a change in gene expression of regulators of the epigenome, in particular, DNMT1, DNMT3a, and methyl CpG binding protein 2 (MeCP2). The modifications of the activity and expression of epigenetic regulators in the hippocampus of rodents perinatally exposed to alcohol suggest that alcohol's impact on the epigenome and its regulators may be one of the underlying mechanisms of alcohol teratogenesis.     

Adolescent brain maturation,the endogenous cannabinoid system and the neurobiology of cannabis-induced schizophrenia

Cannabis use during adolescence increases the risk of developing psychotic disorders later in life. However, the neurobiological processes underlying this relationship are unknown. This review reports the results of a literature search comprising various neurobiological disciplines, ultimately converging into a model that might explain the neurobiology of cannabis-induced schizophrenia. The article briefly reviews current insights into brain development during adolescence. In particular, the role of the excitatory neurotransmitter glutamate in experience-dependent maturation of specific cortical circuitries is examined. The review also covers recent hypotheses regarding disturbances in strengthening and pruning of synaptic connections in the prefrontal cortex, and the link with latent psychotic disorders. In the present model, cannabis-induced schizophrenia is considered to be a distortion of normal late postnatal brain maturation. Distortion of glutamatergic transmission during critical periods may disturb prefrontal neurocircuitry in specific brain areas. Our model postulates that adolescent exposure to Δ9-tetrahydrocannabinol (THC), the primary psychoactive substance in cannabis, transiently disturbs physiological control of the endogenous cannabinoid system over glutamate and GABA release. As a result, THC may adversely affect adolescent experience-dependent maturation of neural circuitries within prefrontal cortical areas. Depending on dose, exact time window and duration of exposure, this may ultimately lead to the development of psychosis or schizophrenia. The proposed model provides testable hypotheses which can be addressed in future studies, including animal experiments, reanalysis of existing epidemiological data, and prospective epidemiological studies in which the role of the dose–time–effect relationship should be central.