Influence of different estrogens on neuroplasticity and cognition in the hippocampus

Background

Estrogens modulate the morphology and function of the hippocampus. Recent studies have focused on the effects of different types of estrogens on neuroplasticity in the hippocampus and cognition. There are three main forms of estrogens found in mammals: estradiol, estrone, and estriol. The vast majority of studies have used estradiol to investigate the effects of estrogens on the brain.

Scope of review

This review focuses on the effects of different estrogens on adult hippocampal neurogenesis, synaptic plasticity in the hippocampus, and cognition in female rats.

Major conclusions

Different forms of estrogens modulate neuroplasticity and cognition in complex and intriguing ways. Specifically, estrogens upregulate adult hippocampal neurogenesis (via cell proliferation) and synaptic protein levels in the hippocampus in a time- and dose-dependent manner. Low levels of estradiol facilitate spatial working memory and contextual fear conditioning while high levels of estradiol impair spatial working, spatial reference memory and contextual fear conditioning. In addition, estrone impairs contextual fear conditioning.

General significance

Advances in our knowledge of how estrogens exert their effects on the brain may ultimately lead to refinements in targeted therapies for cognitive impairments at all stages of life. However caution should be taken in interpreting current research and in conducting future studies as estrogens likely work differently in males than in females.     

Action of estrogens in the aging brain: Dementia and cognitive aging

Background

Menopause is associated with sharp declines in concentrations of circulating estrogens. This change in hormone milieu has the potential to affect brain functions relevant to dementia and cognitive aging.

Scope of review

Focused review of published results of randomized clinical trials of estrogen-containing hormone therapy for Alzheimer's disease treatment and dementia prevention, observational research on cognition across the menopause transition, and observational research on the association of hormone therapy and Alzheimer's disease risk.

Major conclusions

Clinical trial evidence supports conclusions that estrogen therapy does not improve dementia symptoms in women with Alzheimer's disease and that estrogen-containing hormone therapy initiated after about age 65 years increases dementia risk. Hormone therapy begun in this older postmenopausal group does not ameliorate cognitive aging. Cognitive outcomes of midlife hormone exposures are less well studied. There is no strong indication of short-term cognitive benefit of hormone use after natural menopause, but clinical trial data are sparse. Little research addresses midlife estrogen use after surgical menopause; limited clinical trial data imply short-term benefit of prompt initiation at the time of oophorectomy. Whether exogenous estrogen exposures in the early postmenopause affect Alzheimer risk or cognitive aging much later in life is unanswered by available data. Observational results raise the possibility of long-term cognitive benefit, but bias is a concern in interpreting these findings.

General significance

Estrogen-containing hormone therapy should not be initiated after age 65 to prevent dementia or remediate cognitive aging. Further research is needed to understand short-term and long-term cognitive effects of estrogen exposures closer to the age of menopause.     

肿瘤科护士预防导管相关性血流感染认知行为情况调查

目的调查肿瘤科护士预防导管相关性血流感染(CRSBI)的认知与行为情况。方法采用方便抽样法,应用自行设计的"预防CRSBI认知与行为问卷"对107名肿瘤科在职护士进行调查,并进行结果分析。结果 107名护士预防CRSBI知识得分20~105分,平均得分(54.95±14.77)分,平均正确率52.34%。预防CRSBI操作行为得分25~45分,平均得分(39.72±4.26)分。肿瘤科护士预防CRSBI认知情况与工作年限、技术职称和是否接受过CRSBI的知识培训有关,行为情况与是否接受过CRSBI的知识培训有关。结论应加强肿瘤科护士CRSBI相关知识的培训和考核,加强管控,进一步提高肿瘤科护士预防CRSBI的认知水平。     

Establishing a model for assessing DNA damage in murine brain cells as a molecular marker of chemotherapy-associated cognitive impairment

Aims

Chemotherapy-associated cognitive impairment often follows cancer chemotherapy. We explored chemotherapy-induced DNA damage in the brain cells of mice treated with 5-fluorouracil (5FU), an antineoplastic agent, to correlate the extent of DNA damage to behavioral functioning in an autoshaping-operant mouse model of chemotherapy-induced learning and memory deficits (Foley et al., 2008).

Main methods

Male, Swiss-Webster mice were injected once with saline or 75 mg/kg 5FU at 0, 12, and 24 h and weighed every 24 h. Twenty-four h after the last injection, the mice were tested in a two-day acquisition and the retention of a novel response task for food reinforcement. Murine brain cells were analyzed for the presence of single- and double-strand DNA breaks by the single cell gel electrophoresis assay (the Comet assay).

Key findings

We detected significant differences (p < 0.0001) for all DNA damage characteristics (DNA “comet” tail shape, migration pattern, tail moment and olive moments) between control mice cohort and 5FU-treated mice cohort: tail length – 119 vs. 153; tail moment – 101 vs. 136; olive moment – 60 vs. 82, correspondingly. We found a positive correlation between increased response rates (r = 0.52, p < 0.05) and increased rate of errors (r = 0.51, p < 0.05), and DNA damage on day 1. For all 15 mice (saline-treated and 5FU-treated mice), we found negative correlations between DNA damage and weight (r = − 0.75, p < 0.02).

Significance

Our results indicate that chemotherapy-induced DNA damage changes the physiological status of the brain cells and may provide insights to the mechanisms for cognitive impairment after cancer chemotherapy.     

The relationship between IGF-I concentration, cognitive function and quality of life in adults with Prader-Willi syndrome

Mental retardation is one of the clinical characteristics of Prader-Willi syndrome (PWS) and in part of the patients growth hormone deficiency is demonstrable. Cognitive function seems to be influenced by insulin-like growth factor I (IGF-I); however, little is known about cognitive function in relation to IGF-I levels in PWS adults. The aim of the present study was to evaluate cognitive function in adult PWS patients in comparison to healthy siblings and to investigate whether there is a correlation between cognitive function and IGF-I levels. Anthropometric measurements, IGF-I levels, quality of life (QoL), Appetite Assessment Score, IQ (GIT and Raven) and cognitive function (by four subtests of the Cambridge Neuropsychological Automated Testing Battery, CANTAB) were evaluated in PWS patients and their healthy siblings served as control group. PWS patients had significantly lower IGF-I levels, IQ and QoL when compared to controls. Reaction times were longer and performance was worse on CANTAB subtests in PWS adults. IGF-I on one hand and IQ, Appetite Assessment Score and cognitive performance on the other hand seem to be correlated in PWS patients. In conclusion, IGF-I levels, IQ and QoL are significantly lower in PWS subjects when compared to healthy siblings. In PWS adults, temporal as well as prefrontal cognitive functions are impaired. Higher IGF-I levels appear to be related to better intellectual skills and faster temporal memory processing in PWS patients.     

Individuality in nest building: do southern masked weaver (Ploceus velatus) males vary in their nest-building behaviour?

This study investigated how infant pigtailed macaque monkeys performed on two separate learning assessments, two-object discrimination/reversal and Hamilton search learning. Although the learning tasks have been tested on several species, including non-human primates, there have been no normative results reported for young macaque monkeys. The present study provides normative results for these learning tasks in very young captive pigtailed macaques and investigates the degree to which performances on these assessments are related. In addition, an error analysis was conducted to understand the choice patterns of the animals on each task. It was found that males took longer to reach criterion than females on the two-object reversal task. Performance and latency on the discrimination task predicted performance and latency on the reversal task. Performance on Hamilton Search Set-Breaking negatively predicted performance on the later Hamilton Search Forced Set-Breaking task. Finally, latency on reversal significantly predicted the latency on the Hamilton search task. These data provide strong evidence of a relationship between performance on discrimination and reversal. This study shows that, otherwise, each task assesses a different cognitive function.     

Age-related white matter microstructural differences partly mediate age-related decline in processing speed but not cognition

Aging is associated with declining cognitive performance as well as structural changes in brain gray and white matter (WM). The WM deterioration contributes to a disconnection among distributed brain networks and may thus mediate age-related cognitive decline. The present diffusion tensor imaging (DTI) study investigated age-related differences in WM microstructure and their relation to cognition (episodic memory, visuospatial processing, fluency, and speed) in a large group of healthy subjects (n = 287) covering 6 decades of the human life span. Age related decreases in fractional anisotropy (FA) and increases in mean diffusivity (MD) were observed across the entire WM skeleton as well as in specific WM tracts, supporting the WM degeneration hypothesis. The anterior section of the corpus callosum was more susceptible to aging compared to the posterior section, lending support to the anterior-posterior gradient of WM integrity in the corpus callosum. Finally, and of critical interest, WM integrity differences were found to mediate age-related reductions in processing speed but no significant mediation was found for episodic memory, visuospatial ability, or fluency. These findings suggest that compromised WM integrity is not a major contributing factor to declining cognitive performance in normal aging. This article is part of a Special Issue entitled: Imaging Brain Aging and Neurodegenerative disease.     

The influence of exercise on brain aging and dementia

Physical activity has been recognized as an important protective factor reducing disability and mortality and therefore it is focus of many health promotion activities at all ages. More recently a growing body of literature is focusing whether physical activity could also have a positive impact on brain aging with exploring healthy brain aging as well as on cognitive impairment and dementia. An increasing number of prospective studies and randomized controlled trials involving humans take place both with older adults with normal cognition as well as with mild cognitive impairment or dementia. However, the body of evidence is still sparse and many methodological issues make comparisons across studies challenging. Increasingly research into underlying mechanisms in relation to physical activity and brain aging identify biomarker candidates with especially neuroimaging measurements being more used in trials with humans. Whilst the evidence base is slowly growing more detailed research is needed to address methodological issues to finally achieve clinical relevance. This article is part of a Special Issue entitled: Imaging Brain Aging and Neurodegenerative disease.     

Cognitive functioning of adults with Noonan syndrome: a case–control study

Noonan syndrome (NS) is a genetic disorder characterised by short stature, facial dysmorphia, congenital heart defects and mildly lowered intellectual abilities. Research has mainly focused on genetic and somatic aspects, while intellectual and cognitive functioning has been documented scarcely. Also, to date studies have been primarily performed in children. This is the first study in which functioning within the major cognitive domains is systematically evaluated in a group of adults with NS and compared with a control group. Extensive neuropsychological assessment, including the domains intelligence, speed of information processing, memory (working memory, immediate recall and delayed recall), executive function and visuoconstruction, was performed in a sample of 42 patients with NS and 42 healthy controls, matched on age, sex and education level. In addition, subjective cognitive complaints were assessed with self‐report questionnaires. On the domain speed of information processing patients performed worse than controls (P < 0.05). Furthermore, except for slightly better results on delayed recall in the patients with NS (P < 0.05), none of the other cognitive domains showed between‐group differences. On the questionnaires, patients reported substantially more complaints about their own cognitive abilities than controls (P < 0.05). A lowered speed of information processing and relatively intact functioning in other cognitive domains characterises the cognitive profile of adult patients, in contrast to previous findings in children with NS, who seem to have more generalised cognitive deficits.     

Norepinephrine Is Lateralized Within the Olfactory Bulbs of Male Mice

Abstract: Concentrations and in vitro release of norepinephrine were determined from left and right olfactory bulbs of adult male CD-1 mice. Norepinephrine concentrations from the left olfactory bulbs were significantly greater than those of the right ( p < 0.01). No statistically significant differences were obtained for dopamine, nor were there differences in tissue weights between the left and right olfactory bulb tissue samples. To verify further this asymmetry, release rates of norepinephrine were measured from superfused left and right olfactory bulbs. Norepinephrine output from the left olfactory bulb was significantly greater than that from the right ( p < 0.05). These results show that norepinephrine is lateralized within the olfactory bulbs of male mice. This asymmetry shows a clear catecholamine specificity with regard to concentrations and may be related to the lateralized olfactory processing that has been reported to occur in humans.