Microbiome-driven alterations in metabolic pathways and impaired cognition in aged female TgF344-AD rats.

Alzheimer's disease (AD) not only affects cognition and neuropathology, but several other facets capable of negatively impacting quality of life and potentially driving impairments, including altered gut microbiome (GMB) composition and metabolism. Aged (20 + mo) female TgF344-AD and wildtype rats were cognitively characterized on several tasks incorporating several cognitive domains, including task acquisition, object recognition memory, anxiety-like behaviors, and spatial navigation. Additionally, metabolic phenotyping, GMB sequencing throughout the intestinal tract (duodenum, jejunum, ileum, colon, and feces), neuropathological burden assessment and marker gene functional abundance predictions (PICRUSt2) were conducted. TgF344-AD rats demonstrated significant cognitive impairment in multiple domains, as well as regionally specific GMB dysbiosis. Relationships between peripheral factors were investigated using Canonical Correspondence Analysis (CCA), revealing correlations between GMB changes and both cognitive and metabolic factors. Moreover, communities of gut microbes contributing to essential metabolic pathways were significantly altered in TgF344-AD rats. These data indicate dysbiosis may affect cognitive outcomes in AD through alterations in metabolism-related enzymatic pathways that are necessary for proper brain function. Moreover, these changes were mostly observed in intestinal segments required for carbohydrate digestion, not fecal samples. These data support the targeting of intestinal and microbiome health for the treatment of AD.

Astroglia Abnormalities in Post-stroke Mood Disorders.

Stroke is the leading cause of human death and disability. After a stroke, many patients may have some physical disability, including difficulties in moving, speaking, and seeing, but patients may also exhibit changes in mood manifested by depression, anxiety, and cognitive changes which we call post-stroke mood disorders (PSMDs). Astrocytes are the most diverse and numerous glial cell type in the central nervous system (CNS). They provide structural, nutritional, and metabolic support to neurons and regulate synaptic activity under normal conditions. Astrocytes are also critically involved in focal ischemic stroke (FIS). They undergo many changes after FIS. These changes may affect acute neuronal death and brain damage as well as brain recovery and PSMD in the chronic phase after FIS. Studies using postmortem brain specimens and animal models of FIS suggest that astrocytes/reactive astrocytes are involved in PSMD. This chapter provides an overview of recent advances in the molecular base of astrocyte in PSMD. As astrocytes exhibit high plasticity after FIS, we suggest that targeting local astrocytes may be a promising strategy for PSMD therapy.

The Impact of Hormonal Imbalances Associated with Obesity on the Incidence of Endometrial Cancer in Postmenopausal Women.

Obesity has long been associated with endometrial cancer amongst postmenopausal women; in fact, obese women are more than twice as likely to develop endometrial cancer as women of normal weight. The risk of developing this type of cancer increases with weight gains in adulthood, especially among women who did not use hormonal therapy for menopause. Thus, with an association between menopause, obesity, and endometrial cancer established, it prompts the following question: what specific factors could cause higher risk levels for endometrial cancer in this cohort of women? In this paper, the factor of hormonal changes and imbalances associated with both obesity and menopause will be examined. The hormones that will be discussed are insulin and insulin-like factors, estrogen, and adipokines (specifically adiponectin, visfatin, and leptin).