Increased excitability of dentate gyrus mossy cells occurs early in life in the Tg2576 model of Alzheimer's disease.

INTRODUCTION: Hyperexcitability in Alzheimer's disease (AD) emerge early and contribute to disease progression. The dentate gyrus (DG) is implicated in hyperexcitability in AD. We hypothesized that mossy cells (MCs), regulators of DG excitability, contribute to early hyperexcitability in AD. Indeed, MCs generate hyperexcitability in epilepsy. METHODS: Using the Tg2576 model and WT mice (∼1month-old), we compared MCs electrophysiologically, assessed c-Fos activity marker, Aß expression and mice performance in a hippocampal-dependent memory task. RESULTS: Tg2576 MCs exhibit increased spontaneous excitatory events and decreased inhibitory currents, increasing the charge transfer excitation/inhibition ratio. Tg2576 MC intrinsic excitability was enhanced, and showed higher c-Fos, intracellular Aß expression, and axon sprouting. Granule cells only showed changes in synaptic properties, without intrinsic changes. The effects occurred before a memory task is affected. DISCUSSION: Early electrophysiological and morphological alterations in Tg2576 MCs are consistent with enhanced excitability, suggesting an early role in DG hyperexcitability and AD pathophysiology. HIGHLIGHTS: ∘ MCs from 1 month-old Tg2576 mice had increased spontaneous excitatory synaptic input. ∘ Tg2576 MCs had reduced spontaneous inhibitory synaptic input. ∘ Several intrinsic properties were abnormal in Tg2576 MCs. ∘ Tg2576 GCs had enhanced synaptic excitation but no changes in intrinsic properties. ∘ Tg2576 MCs exhibited high c-Fos expression, soluble Aß and axonal sprouting.

Increasing adult neurogenesis protects mice from epilepsy.

Neurogenesis occurs in the adult brain in the hippocampal dentate gyrus, an area that contains neurons which are vulnerable to insults and injury, such as severe seizures. Previous studies showed that increasing adult neurogenesis reduced neuronal damage after these seizures. Because the damage typically is followed by chronic lifelong seizures (epilepsy), we asked if increasing adult neurogenesis would prevent epilepsy. Adult neurogenesis was selectively increased by deleting the pro-apoptotic gene Bax from Nestin-expressing progenitors. Tamoxifen was administered at 6 weeks of age to conditionally delete Bax in Nestin-CreERT2Baxfl/fl mice. Six weeks after tamoxifen administration, severe seizures (status epilepticus; SE) were induced by injection of the convulsant pilocarpine. Mice with increased adult neurogenesis exhibited fewer chronic seizures. Postictal depression was reduced also. These results were primarily female mice, possibly because they were the more affected by Bax deletion than males, consistent with sex differences in Bax in development. The female mice with enhanced adult neurogenesis also showed less neuronal loss of hilar mossy cells and hilar somatostatin-expressing neurons than wild type females or males, which is notable because these two cell types are implicated in epileptogenesis. The results suggest that increasing adult neurogenesis in the normal adult brain can reduce experimental epilepsy, and the effect shows a striking sex difference. The results are surprising in light of past studies showing that suppressing adult-born neurons can also reduce chronic seizures.

Medicine and History: a Surgical Model for National Integration.

Historians and physicians have struggled to incorporate history into American medical education for over a century. Most efforts focus on local initiatives targeting a narrow audience. We describe a novel method involving the American College of Surgeons, a national organization with tens of thousands of members. Capitalizing on its infrastructure and influence over the field, we have implemented a variety of ventures that include panel sessions at meetings, poster competitions, travel grants, themed breakfasts, online communities, and other such projects. This programming has reached thousands of participants, ranging from pre-medical students to retired physicians, and it has increased both the exposure to and production of surgical history. Our article describes the process of establishing this nationally coordinated enterprise in the hopes that other medical specialties can emulate it and further the study of and appreciation for medical history.

Photosynthesis and respiration of the soft coral Xenia umbellata respond to warming but not to organic carbon eutrophication.

Eutrophication with dissolved organic carbon (DOC) as a far under-investigated stressor, and ocean warming, can strongly affect coral reefs and hard corals as major reefs ecosystem engineers. However, no previous studies have investigated the metabolic responses of soft corals to DOC eutrophication, or its interaction with ocean warming. Thus, we investigated respiration and photosynthesis response of Xenia umbellata, a common mixotrophic soft coral from the Indo-pacific, to (1) three levels of DOC eutrophication simulated by glucose addition over the first 21 days of experiment and (2) ocean warming scenarios where the temperature was gradually increased from 26 °C (control condition) to 32 °C over another 24 days in an aquarium experiment. We found no significant difference in response to DOC treatments and all corals survived regardless of the DOC concentrations, whilst subsequent exposure to simulated ocean warming significantly decreased gross photosynthesis by approximately 50% at 30 °C, and 65% at 32 °C, net photosynthesis by 75% at 30 °C and 79% at 32 °C, and respiration by a maximum of 75% at 30 °C; with a slight increase at 32 °C of 25%. The ratio between gross photosynthesis and respiration decreased by the end of the warming period but remained similar between controls and colonies previously exposed to DOC. Our findings suggest that soft corals may be more resistant than hard corals to DOC eutrophication and in consequence, may potentially experiment in less magnitude the negative effects of increased temperature or subsequently both stressors. The results of this study may contribute to explain the successful role of soft corals in phase shifts as reported from many coral reefs. Where predicted declines in reef ecosystems health due to increased eutrophication levels can be exacerbated by future warming.

Thermal variation and factors influencing vertical migration behavior in Daphnia populations.

The antipredator behavior diel vertical migration (DVM), common in aquatic keystone species Daphnia, involves daily migration from warmer surface waters before dawn to cooler deeper waters after dusk. Plasticity in Daphnia DVM behavior optimizes fitness via trade-offs between growth, reproduction, and predator avoidance. Migration behavior is affected by co-varying biotic and abiotic factors, including light, predator cues, and anthropogenic stressors making it difficult to determine each factor's individual contribution to the variation in this behavior. This study aims to better understand this ecologically significant behavior in Daphnia by: (1) determining how Daphnia pulicaria thermal preferences vary within and among natural populations; (2) distinguishing the role of temperature verses depth in Daphnia vertical migration; and (3) defining how two anthropogenic stressors (copper and nickel) impact Daphnia migratory behavior. Simulated natural lake stratification were constructed in 8L (0.5m tall, 14.5cm wide) water columns to monitor under controlled laboratory conditions the individual effects of temperature gradients, depth, and metal stressors on Daphnia vertical migration. Three major findings are reported. First, while no difference in thermal preference was found among the four populations studied, within lake populations variability among isolates was high. Second, decoupling temperature and depth revealed that depth was a better predictor of Daphnia migratory patterns over temperature. Third, exposure to environmentally relevant concentrations of copper or nickel inhibited classic DVM behavior. These findings revealed the high variability in thermal preference found within Daphnia populations, elucidated the individual roles that depth and temperature have on migratory behavior, and showed how copper and nickel can interfere with the natural response of Daphnia to fish predator cues. Thus contributing to the body of knowledge necessary to predict how natural populations of Daphnia will be affected by climate related changes in lake temperatures and increased presence of anthropogenic stressors.

Effect of text message follow-up on patient's self-reported level of pain and anxiety.

OBJECTIVES: To determine whether a text message reduces the severity of patient self-reported levels of pain and anxiety following initial placement of orthodontic appliances. MATERIALS AND METHODS: Thirty-nine orthodontic patients were randomly assigned to one of two groups and matched for age, gender, and bracket type (self-ligating vs conventional). The subjects completed baseline questionnaires to ascertain their levels of pain and anxiety before initiating orthodontic treatment. Following the initial appointment, subjects completed the pain questionnaire and anxiety inventory at the same time daily for 1 week. One group received a structured text message showing concern and reassurance, while the second group served as a control and received no postprocedural communication. RESULTS: There was a statistically significant difference in pain in relation to time between the text message group and the control group as it was demonstrated that demonstrated that compared with the text message group, mean pain intensity increased and selfreported discomfort was longer in the control group. Anxiety was determined to be at its peak the day following initial orthodontic appliance placement and gradually tapered off from that time point. No intergroup difference was noted when analyzing anxiety. CONCLUSIONS: This study demonstrated that a text message sent from an orthodontic office following initial appliance placement resulted in a lower level of patient's self-reported pain. Additionally, patient anxiety is at its peak the day following the initial appointment and decreases from that point forward.