The Neuroprotective Effect Of Decreased Luteinizing Hormone On Astrocytic Pathology In An Alzheimer\u27s Disease Model

After menopause or ovariectomy (ovx) females have high levels of luteinizing hormone (LH) which may contribute to and exacerbate Alzheimer’s disease (AD). High levels of LH have been associated with decreased spatial memory and increased amyloid-beta levels, both characteristic of Alzheimer’s disease. Conversely, by decreasing levels of this hormone, studies have been able to improve the memory of normal, nonAD rats and recover memory deficits in animal models of AD. Based on this research, it was hypothesized that female rats with low, as compared to high, levels of LH would show less hippocampal damage in an animal model of AD. To create an Alzheimer’s disease model, the neurotoxins amyloid-beta and ibotenic acid were infused into the hippocampus of female Sprague-Dawley rats. To vary LH levels, rats were either ovx so they had high LH levels or were ovx and given Antide, a GnRH antagonist that decreases LH levels. Antide or vehicle were administered either 1d before (early Antide) or beginning 4d after (late Antide) the neurotoxin infusion. This resulted in 4 groups of ovx females: Control, AD, AD + early Antide, and AD + late Antide. Damage was ascertained using immunocytochemistry for glial fibrillary acidic protein (GFAP), an intermediate filament protein specific to astrocytes of the central nervous system. Astrocytic pathology within the CA1 region of the hippocampus was determined by the number of GFAP immunoreactive cells, astrocyte cell size, and GFAP content (area covered by stained pixels). Ovx AD females had an increased number of GFAP-containing cells, increased astrocytic cell size, and increased GFAP content compared to ovx control animals. Early Antide treatment prior to neurotoxin infusion resulted in a decreased cell number and a decreased GFAP content compared to the AD group. Furthermore, while AD+late Antide treatment had no effect on cell number compared to the AD females, it did result in decreased GFAP content. Lastly, cell size for both Antide treatment groups was intermediate between the AD and control groups. These results provide evidence that low levels of LH results in decreased neural damage in CA1 in an AD model. This suggests that high levels of LH such as those seen after menopause are harmful to the hippocampus and may contribute to the damage seen during AD, and that an LH antagonist could play either a preventative and/or therapeutic role in the treatment of Alzheimer’s disease

The androgen receptor governs the execution, but not programming, of male sexual and territorial behaviors

Testosterone and estrogen are essential for male behaviors in vertebrates. How these two signaling pathways interact to control masculinization of the brain and behavior remains to be established. Circulating testosterone activates the androgen receptor (AR) and also serves as the source of estrogen in the brain. We have used a genetic strategy to delete AR specifically in the mouse nervous system. This approach permits us to determine the function of AR in sexually dimorphic behaviors in males while maintaining circulating testosterone levels within the normal range. We find that AR mutant males exhibit masculine sexual and territorial displays, but they have striking deficits in specific components of these behaviors. Taken together with the surprisingly limited expression of AR in the developing brain, our findings indicate that testosterone acts as a precursor to estrogen to masculinize the brain and behavior, and signals via AR to control the levels of male behavioral displays

Using Stakeholder Value Analysis to Build Exploration Sustainability

Abstract: The sustainability of space exploration will depend in large part on its ability to consistently and reliably deliver valued benefits to societal stakeholders over an extended period. This on-going research studies the values of prospective stakeholders in the space exploration enterprise—both in the near term and with a perspective extending over decades. The immediate focus is human and robotic exploration of the Earth/Moon system, but extends to the exploration of Mars as well. Potential beneficiaries of space exploration are identified in broad societal sectors. An analysis of these stakeholders, their values and needs leads to the development of a comprehensive set of space exploration objectives that address those needs. The relative priority of exploration objectives is weighted using information about stakeholder characteristics, values, and their role and place in the exploration value stream. The weighted exploration objectives can then be used to assess the relative value of different technical system architectures, and to design exploration enterprise architecture, attributes and policy frameworks to enable value delivery to societal stakeholders. Ultimately, through stakeholders ’ continuing support, sustainable space exploration will be delivered. I

Gut microbiome, liver immunology, and liver diseases

The gut microbiota is a complex and plastic consortium of microorganisms that are intricately connected with human physiology. The liver is a central immunological organ that is particularly enriched in innate immune cells and constantly exposed to circulating nutrients and endotoxins derived from the gut microbiota. The delicate interaction between the gut and liver prevents accidental immune activation against otherwise harmless antigens. Work on the interplay between the gut microbiota and liver has assisted in understanding the pathophysiology of various liver diseases. Of immense importance is the step from high-throughput sequencing (correlation) to mechanistic studies (causality) and therapeutic intervention. Here, we review the gut microbiota, liver immunology, and the interaction between the gut and liver. In addition, the impairment in the gut–liver axis found in various liver diseases is reviewed here, with an emphasis on alcohol-associated liver disease (ALD), nonalcoholic fatty liver disease (NAFLD), and autoimmune liver disease (AILD). On the basis of growing evidence from these preclinical studies, we propose that the gut–liver axis paves the way for targeted therapeutic modalities for liver diseases