Immunocytochemistry with antibodies to ubiquitin is currently the most sensitive method for detecting cortical Lewy bodies, which are a sine qua non for the diagnosis of diffuse Lewy body disease (DLBD), an increasingly recognized form of primary degenerative dementia. In the systematic application of ubiquitin immunocytochemistry to sections of hippocampus from control subjects and patients with a wide spectrum of neurodegenerative diseases, we noted the frequent occurrence of ubiquitin-immunoreactive neurites in the CA2-3 region in DLBD. The nature of these neurites was investigated with immunocytochemistry in DLBD, Alzheimer's disease (AD), normal elderly subjects, and Parkinson's disease (PD). Although the number of neurites varied from case to case, they were virtually always detected in DLBD but not in normal, AD, or PD brains. Double immunolabeling studies with anti-ubiquitin demonstrated a small fraction of double-stained neurites with antibodies to neurofilament or Alz-50, but no double staining with an antibody to Alzheimer neurofibrillary tangles. These results are different from those for neurites in AD, which are rarely seen in CA2-3 and which are immunoreactive with all these antibodies. Neuritic degeneration in the CA2-3 region of the hippocampus appears to be a specific histopathologic feature of DLBD.

Ghrelin, an orexigenic hormone, is mainly produced by the stomach and released into the circulation. Ghrelin receptors (growth hormone secretagogue receptors) are expressed throughout the brain, including the hippocampus. The activation of ghrelin receptors facilitates high-frequency stimulation (HFS)-induced long-term potentiation (LTP) in vitro, and also improves learning and memory. Herein, we report that a single infusion of ghrelin into the hippocampus led to long-lasting potentiation of excitatory postsynaptic potentials (EPSPs) and population spikes (PSs) in the dentate gyrus of anesthetized rats. This potentiation was accompanied by a reduction in paired-pulse depression of the EPSP slope, an increase in paired-pulse facilitation of the PS amplitude, and an enhancement of EPSP-spike coupling, suggesting the involvement of both presynaptic and postsynaptic mechanisms. Meanwhile, ghrelin infusion time-dependently increased the phosphorylation of Akt-Ser473, a downstream molecule of phosphoinositide 3-kinase (PI3K). Interestingly, PI3K inhibitors, but not NMDA receptor antagonist, inhibited ghrelin-induced potentiation. Although ghrelin had no effect on the induction of HFS-induced LTP, it prolonged the expression of HFS-induced LTP through extracellular signal-regulated kinase (ERK)1/2. The Morris water maze test showed that ghrelin enhanced spatial memory, and that this was prevented by pretreatment with PI3K inhibitor. Taken together, the findings show that: (i) a single infusion of ghrelin induced a new form of synaptic plasticity by activating the PI3K signaling pathway, without HFS and NMDA receptor activation; (ii) a single infusion of ghrelin also enhanced the maintenance of HFS-induced LTP through ERK activation; and (iii) repetitive infusion of ghrelin enhanced spatial memory by activating the PI3K signaling pathway. Thus, we propose that the ghrelin signaling pathway could have therapeutic value in cognitive deficits.

BackgroundThe growing applications of nanotechnologic products, such as quantum dots (QDs), increase the likelihood of exposure. Furthermore, their accumulation in the bioenvironment and retention in cells and tissues are arousing increasing worries about the potentially harmful side effects of these nanotechnologic products. Previous studies concerning QD cytotoxicity focused on the reactive oxygen species produced by QDs. Cellular calcium homeostasis dysregulation caused by QDs may be also responsible for QD cytotoxicity. Meanwhile the interference of QDs with voltage-gated sodium channel (VGSC) current (INa) may lead to changes in electrical activity and worsen neurotoxicologic damage.ObjectiveWe aimed to investigate the potential for neurotoxicity of cadmium selenium QDs in a hippocampal neuronal culture model, focusing on cytoplasmic calcium levels and VGSCs function.MethodsWe used confocal laser scanning and standard whole-cell patch clamp techniques.ResultsWe found that a) QDs induced neuron death dose dependently; b) cytoplasmic calcium levels were elevated for an extended period by QD treatment, which was due to both extracellular calcium influx and internal calcium release from endoplasmic reticulum; and c) QD treatment enhanced activation and inactivation of INa, prolonged the time course of activation, slowed INa recovery, and reduced the fraction of available VGSCs.ConclusionResults in this study provide new insights into QD toxicology and reveal potential risks of their future applications in biology and medicine.

BackgroundAttention deficit/hyperactivity disorder (ADHD) and lead exposure are high-prevalence conditions among children.ObjectiveOur goal was to investigate the association between ADHD and blood lead levels (BLLs) in Chinese children, adjusting for known ADHD risk factors and potential confounding variables.MethodsWe conducted a pair-matching case–control study with 630 ADHD cases and 630 non-ADHD controls 4–12 years of age, matched on the same age, sex, and socioeconomic status. The case and control children were systematically evaluated via structured diagnostic interviews, including caregiver interviews, based on the Diagnostic and Statistical Manual of Mental Disorders, 4th ed., revised criteria (DSM-IV-R). We evaluated the association between BLLs and ADHD using the Pearson chi-square test for categorical variables and the Student t-test for continuous data. We then performed conditional multiple variables logistic regression analyses with backward stepwise selection to predict risk factors for ADHD.ResultsThere was a significant difference in BLLs between ADHD cases and controls. ADHD cases were more likely to have been exposed to lead during childhood than the non-ADHD control subjects, with adjustment for other known risk factors [children with BLLs ≥ 10 μg/dL vs. ≤ 5 μg/dL; OR = 6.0; 95% confidence interval (CI) = 4.10–8.77, p < 0.01; 5–10 μg/dL vs.≤ 5 μg/dL, OR = 4.9; 95% CI = 3.47–6.98, p < 0.01]. These results were not modified by age and sex variables.ConclusionsThis was the largest sample size case–control study to date to study the association between BLLs and ADHD in Chinese children. ADHD may be an additional deleterious outcome of lead exposure during childhood, even when BLLs are < 10 μg/dL.

With the increasing applications of titanium dioxide nanoparticles (TiO(2) NPs) in industry and daily life, an increasing number of studies showed that TiO(2) NPs may have negative effects on the respiratory or metabolic circle systems of organisms, while very few studies focused on the brain central nervous system (CNS). Synaptic plasticity in hippocampus is believed to be associated with certain high functions of CNS, such as learning and memory. Thus, in this study, we investigated the effects of developmental exposure to TiO(2) NPs on synaptic plasticity in rats' hippocampal dentate gyrus (DG) area using in vivo electrophysiological recordings. The input/output (I/O) functions, paired-pulse reaction (PPR), field excitatory postsynaptic potential, and population spike amplitude were measured. The results showed that the I/O functions, PPR, and long-term potentiation were all attenuated in lactation TiO(2) NPs-exposed offspring rats compared with those in the control group. However, in the pregnancy TiO(2) NPs exposure group, only PPR was attenuated significantly. These findings suggest that developmental exposure to TiO(2) NPs could affect synaptic plasticity in offspring's hippocampal DG area in vivo, which indicates that developmental brains, especially in lactation, are susceptible to TiO(2) NPs exposure. This study reveals the potential toxicity of TiO(2) NPs in CNS. It may give some hints on the security of TiO(2) NPs production and application and shed light on its future toxicological studies.