Correction to Rhodes et al. (2003): Exercise Increases Hippocampal Neurogenesis to High Levels but Does Not Improve Spatial Learning in Mice Bred for Increased Voluntary Wheel Running.

Reports an error in the original article by Justin S. Rhodes, Henriette van Praag, Susan Jeffrey, Isabelle Girard, Gordon S. Mitchell, Theodore Garland Jr., and Fred H. Gage (Behavioral Neuroscience, 2003, Vol. 117, No. 5, pp. 1006-1016. In Figure 3, the symbols representing the "Control runners" and "Selected no wheels" groups were reversed in Panel B. They should match the legend in Panel A: Open circles should appear as solid squares, and solid squares as open circles. (The following abstract of this article originally appeared in record 2003-08567-013.) The hippocampus is important for the acquisition of new memories. It is also one of the few regions in the adult mammalian brain that can generate new nerve cells. The authors tested the hypothesis that voluntary exercise increases neurogenesis and enhances spatial learning in mice selectively bred for high levels of wheel running (S mice). Female S mice and outbred control (C) mice were housed with and without running wheels for 40 days. 5-Bromodeoxyuridine was used to label dividing cells. The Morris water maze was used to measure spatial learning. C runners showed a strong positive correlation between running distance and new cell number, as well as improved learning. In S runners, neurogenesis increased to high levels... (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

One-Trial Odor-Reward Association: A Form of Event Memory Not Dependent on Hippocampal Function.

To examine whether the hippocampus is required for memory for unique experiences independent of their spatial or temporal context, the authors devised a novel task that requires rats to remember odor-reward associations formed within a single training trial. Unlike previous tests of 1-trial memory, in this task new associations with otherwise familiar stimuli must be formed, and accurate judgments cannot be based on relative familiarity or recency of the stimuli. The authors show that intact rats performed well on this novel test of event memory. Furthermore, rats with lesions of the hippocampus showed no impairments, even over long retention intervals. These data suggest that the hippocampus is not required for event-specific stimulus-reward associations and that other brain structures mediate this aspect of episodic memory. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Melatonin Stimulates Dendrite Formation and Complexity in the Hilar Zone of the Rat Hippocampus: Participation of the Ca++/Calmodulin Complex

Melatonin (MEL), the main product synthesized by the pineal gland, stimulates early and late stages of neurodevelopment in the adult brain. MEL increases dendrite length, thickness and complexity in the hilar and mossy neurons of hippocampus. Dendrite formation involves activation of Ca²⁺/Calmodulin (CaM)-dependent kinase II (CaMKII) by CaM. Previous work showed that MEL increased the synthesis and translocation of CaM, suggesting that MEL activates CaM-dependent enzymes by this pathway. In this work we investigated whether MEL stimulates dendrite formation by CaMKII activation in organotypic cultures from adult rat hippocampus. We found that the CaMKII inhibitor, KN-62, abolished the MEL stimulatory effects on dendritogenesis and that MEL increased the relative amount of CaM in the soluble fraction of hippocampal slices. Also, PKC inhibition abolished dendritogenesis, while luzindole, an antagonist of MEL receptors (MT1/2), partially blocked the effects of MEL. Moreover, autophosphorylation of CaMKII and PKC was increased in presence of MEL, as well as phosphorylation of ERK1/2. Our results indicate that MEL stimulates dendrite formation through CaMKII and the translocation of CaM to the soluble fraction. Dendritogenesis elicited by MEL also required PKC activation, and signaling through MT1/2 receptors was partially involved. Data strongly suggest that MEL could repair the loss of hippocampal dendrites that occur in neuropsychiatric disorders by increasing CaM levels and activation of CaMKII.     

Prophylactic Therapy with Human Amniotic Fluid Stem Cells Improves Long-Term Cognitive Impairment in Rat Neonatal Sepsis Survivors

A systemic inflammatory response induces multiple organ dysfunction and results in poor long-term neurological outcomes in neonatal sepsis. However, there is no effective therapy for treating or preventing neonatal sepsis besides antibiotics and supportive care. Therefore, a novel strategy to improve neonatal sepsis-related morbidity and mortality is desirable. Recently, we reported that prophylactic therapy with human amniotic stem cells (hAFSCs) improved survival in a rat model of lipopolysaccharide (LPS)-induced neonatal sepsis through immunomodulation. Besides improving the mortality, increasing survival without major morbidities is an important goal of neonatal intensive care for neonatal sepsis. This study investigated long-term neurological outcomes in neonatal sepsis survivors treated with hAFSCs using the LPS-induced neonatal sepsis model in rats. We found that prophylactic therapy with hAFSCs improved spatial awareness and memory-based behavior in neonatal sepsis survivors at adolescence in rats. The treatment suppressed acute reactive gliosis and subsequently reduced astrogliosis in the hippocampal region over a long period of assessment. To the best of our knowledge, this is the first report that proves the concept that hAFSC treatment improves cognitive impairment in neonatal sepsis survivors. We demonstrate the efficacy of hAFSC therapy in improving the mortality and morbidity associated with neonatal sepsis.     

GAD65基因修饰的神经干细胞移植治疗癫痫的实验研究

目的:将谷氨酸脱羧酶65(GAD65)基因修饰的神经干细胞移植到海仁酸颞叶癫痫模型大鼠海马中,检测目的基因在脑内的表达以及基因工程化细胞移植对癫痫的影响.方法:建立海仁酸致癫痫大鼠模型,完全随机分为GAD-NSCs移植组、单纯NSCs移植组、生理盐水对照组,每组20只.在移植后1、2、3天,1、2、4、8周各时间点,通...     

Cardiorespiratory fitness, hippocampal volume, and frequency of forgetting in older adults.

Objective: The purpose of this study was to extend our earlier work to determine the extent to which cardiorespiratory fitness is associated with the frequency of memory problems via its effects on the hippocampus and spatial working memory. We hypothesized that age, sex, education, body composition, and physical activity were direct determinants of fitness, which, in turn, influenced frequency of forgetting indirectly through hippocampal volume and spatial working memory. Method: We conducted assessments of demographic characteristics, Body Mass Index (BMI), physical activity, cardiorespiratory fitness, hippocampal volume, spatial working memory, and frequency of forgetting in 158 older adults (M age = 66.49). Path analyses within a covariance modeling framework were used to examine relationships among these constructs. Results: Sex, age, BMI, and education were all significant determinants of cardiorespiratory fitness. The hypothesized path models for testing the effects of fitness on frequency of forgetting through hippocampal volume and accuracy and speed of spatial working memory all fit the data well. Conclusions: Our findings suggest that older adults with higher levels of fitness show greater preservation of hippocampal volume, which, in turn, is associated with more accurate and faster spatial memory and fewer episodes of forgetting. Given the proportion of older adults reporting memory problems, it is necessary to determine whether improvements in fitness brought about by physical activity interventions can result in subsequent attenuation of memory problems or potentially in improvements in memory. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Pattern memory involves both elemental and configural processes: Evidence from the effects of hippocampal lesions.

The formation of an integrated memory for a pattern of stimulation could be based on the elements of that pattern becoming directly linked to one another, or by each of the elements becoming linked to a shared separate configural representation. These 2 accounts have proven difficult to discriminate between. Here, rats received exposure to four patterns of stimulation, each consisting of an auditory stimulus, a visual context, and a time of day; and we examined whether pre-training lesions to the hippocampus influenced memory for the patterns. These lesions abolished pattern memory that required configural processes (Experiments 1A and 1B) but had no effect on pattern memory that could be supported by elemental processes (Experiment 2). This dissociation provides support for the views that elemental and configural processes ordinarily support pattern memory and that rats with lesions to the hippocampus are left reliant on elemental processes. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Estradiol's effects on learning and neuronal morphology vary with route of administration.

Estrogen's effects on performance and neuronal morphology are variable, and the reasons for this variability are not yet understood. In this study, the authors compared the effects of 2 delivery routes of 17 β-estradiol on spatial learning and dendritic spine densities in young ovariectomized rats; estradiol was administered by implanted capsules or by daily oral gavage. Estradiol treatment via capsules improved performance in the radial-arm water maze and increased spine densities on dendrites of CA1 pyramidal neurons in the hippocampal formation. In contrast, daily oral administration of estradiol did not affect either measure. These data demonstrate that estradiol delivery is a critical variable in animal studies and that clinical studies comparing the effects of different estradiol treatment routes on cognition are warranted. (PsycINFO Database Record (c) 2010 APA, all rights reserved)