Sexual dimorphism, altered hippocampal glutamatergic neurotransmission, and cognitive impairment in APP knock-in mice.

Background: It is well established that glutamatergic neurotransmission plays an essential role in learning and memory. Previous studies indicate that glutamate dynamics shift with Alzheimer's disease (AD) progression, contributing to negative cognitive outcomes.

Objective: In this study, we characterized hippocampal glutamatergic signaling with age and disease progression in a knock-in mouse model of AD (APP).

Senolytic intervention improves cognition, metabolism, and adiposity in female APP mice.

Senescent cells accumulate throughout the body and brain contributing to unhealthy aging and Alzheimer's disease (AD). The APP amyloidogenic AD mouse model exhibits increased markers of senescent cells and the senescence-associated secretory phenotype (SASP) in visceral white adipose tissue and the hippocampus before plaque accumulation and cognitive decline. We hypothesized that senolytic intervention would alleviate cellular senescence thereby improving spatial memory in APP mice.

Microglial Piezo1 mechanosensitive channel as a therapeutic target in Alzheimer's disease.

Microglia are the resident macrophages of the central nervous system (CNS) that control brain development, maintain neural environments, respond to injuries, and regulate neuroinflammation. Despite their significant impact on various physiological and pathological processes across mammalian biology, there remains a notable gap in our understanding of how microglia perceive and transmit mechanical signals in both normal and diseased states. Recent studies have revealed that microglia possess the ability to detect changes in the mechanical properties of their environment, such as alterations in stiffness or pressure.

Thermotherapy has Sexually Dimorphic Responses in APP/PS1 Mice.

A thermoregulatory decline occurs with age due to changes in muscle mass, vasoconstriction, and metabolism that lowers core body temperature (Tc). Although lower Tc is a biomarker of successful aging, we have previously shown this worsens cognitive performance in the APP/PS1 mouse model of Alzheimer's disease (AD) [1]. We hypothesized that elevating Tc with thermotherapy would improve metabolism and cognition in APP/PS1 mice.

Senolytic Intervention Improves Cognition, Metabolism, and Adiposity in Female APP Mice.

Senescent cells accumulate throughout the body and brain contributing to unhealthy aging and Alzheimer's disease (AD). The APP amyloidogenic AD mouse model exhibits increased markers of senescent cells and the senescence-associated secretory phenotype (SASP) in visceral white adipose tissue before plaque accumulation and cognitive decline. We hypothesized that senolytic intervention would alleviate cellular senescence thereby improving spatial memory in APP mice.

Sex-Dependent Effects of Chronic Circadian Disruption in AβPP/PS1 Mice.

Background: Chronic disruption of the circadian timing system, often reflected as a loss of restful sleep, also includes myriad other pathophysiological effects.

Objective: The current study examined how chronic circadian disruption (CD) could contribute to pathology and rate of progression in the AβPP/PS1 mouse model of Alzheimer's disease (AD).

Methods: A chronic CD was imposed until animals reached 6 or 12 months of age in AβPP/PS1 and C57BL/6J control mice.

Sexual Dimorphism, Altered Hippocampal Glutamatergic Neurotransmission and Cognitive Impairment in APP Knock-In Mice.

Background: It is well established that glutamatergic neurotransmission plays an essential role in learning and memory. Previous studies indicate that glutamate dynamics shift with Alzheimer's disease (AD) progression, contributing to negative cognitive outcomes.

Objective: In this study, we characterized hippocampal glutamatergic signaling with age and disease progression in a knock-in mouse model of AD (APP).

Relationships among Development, Growth, Body Size, Reproduction, Aging, and Longevity - Trade-Offs and Pace-Of-Life.

Relationships of growth, metabolism, reproduction, and body size to the biological process of aging and longevity have been studied for decades and various unifying "theories of aging" have been proposed to account for the observed associations. In general, fast development, early sexual maturation leading to early reproductive effort, as well as production of many offspring, have been linked to shorter lifespans. The relationship of adult body size to longevity includes a remarkable contrast between the positive correlation in comparisons between different species and the negative correlation seen in comparisons of individuals within the same species.

Sexual dimorphic metabolic and cognitive responses of C57BL/6 mice to Fisetin or Dasatinib and quercetin cocktail oral treatment.

Senolytic treatment in aged mice clears senescent cell burden leading to functional improvements. However, less is known regarding the effects of these compounds when administered prior to significant senescent cell accumulation. From 4-13 months of age, C57BL/6 male and female mice received monthly oral dosing of either 100 mg/kg Fisetin or a 5 mg/kg Dasatinib (D) plus 50 mg/kg Quercetin (Q) cocktail.

Prodromal Glutamatergic Modulation with Riluzole Impacts Glucose Homeostasis and Spatial Cognition in Alzheimer's Disease Mice.

Background: Prior research supports a strong link between Alzheimer's disease (AD) and metabolic dysfunction that involves a multi-directional interaction between glucose, glutamatergic homeostasis, and amyloid pathology. Elevated soluble amyloid-β (Aβ) is an early biomarker for AD-associated cognitive decline that contributes to concurrent glutamatergic and metabolic dyshomeostasis in humans and male transgenic AD mice. Yet, it remains unclear how primary time-sensitive targeting of hippocampal glutamatergic activity may impact glucose regulation in an amyloidogenic mouse model.

Responses to Many Anti-Aging Interventions Are Sexually Dimorphic.

There is increasing appreciation that sex differences are not limited to reproductive organs or traits related to reproduction and that sex is an important biological variable in most characteristics of a living organism. The biological process of aging and aging-related traits are no exception and exhibit numerous, often major, sex differences. This article explores one aspect of these differences, namely sex differences in the responses to anti-aging interventions.

Health disparities in aging: Improving dementia care for Black women.

In the United States, 80% of surveyed Black patients report experiencing barriers to healthcare for Alzheimer's disease and related dementias (ADRD), delaying the time-sensitive treatment of a progressive neurodegenerative disease. According to the National Institute on Aging, Black study participants are 35% less likely to be given a diagnosis of ADRD than white participants, despite being twice as likely to suffer from ADRD than their white counterparts. Prior analysis of prevalence for sex, race, and ethnicity by the Centers for Disease Control indicated the highest incidence of ADRD in Black women.

Resistance to mild cold stress is greater in both wild-type and long-lived GHR-KO female mice.

Adapting to stress, including cold environmental temperature (eT), is crucial for the survival of mammals, especially small rodents. Long-lived mutant mice have enhanced stress resistance against oxidative and non-oxidative challenges. However, much less is known about the response of those long-lived mice to cold stress.

Chronic, Mild Hypothermic Environmental Temperature Does Not Ameliorate Cognitive Deficits in an Alzheimer's Disease Mouse.

Metabolic dysfunction increases with age and is a contributing factor to Alzheimer's disease (AD) development. We have previously observed impaired insulin sensitivity and glucose homeostasis in the APP/PS1 model of AD. To improve these parameters, we chronically exposed male and female mice to mild hypothermic environmental temperature (eT), which positively modulates metabolism.

Friend or Foe? Defining the Role of Glutamate in Aging and Alzheimer's Disease.

Aging is a naturally occurring decline of physiological processes and biological pathways that affects both the structural and functional integrity of the body and brain. These physiological changes reduce motor skills, executive function, memory recall, and processing speeds. Aging is also a major risk factor for multiple neurodegenerative disorders including Alzheimer's disease (AD).

Psychological Resilience and Cognitive Function Among Older Military Veterans.

The purpose of this study was to explore the association between psychological resilience and cognitive function in military veterans. We obtained public-use data from the Health and Retirement Study (HRS) for this cross-sectional study of military veterans aged 52 to 101 years ( = 150). We estimated a multivariable linear regression model in which cognitive function served as the dependent variable and psychological resilience served as the independent variable.

Amyloid-β stimulated hippocampal lactate release is coupled to glutamate uptake.

Since brain glucose hypometabolism is a feature of Alzheimer's disease (AD) progression, lactate utilization as an energy source may become critical to maintaining central bioenergetics. We have previously shown that soluble amyloid-β (Aβ) stimulates glutamate release through the α7 nicotinic acetylcholine receptor (α7nAChR) and hippocampal glutamate levels are elevated in the APP/PS1 mouse model of AD. Accordingly, we hypothesized that increased glutamate clearance contributes to elevated extracellular lactate levels through activation of the astrocyte neuron lactate shuttle (ANLS).

Assessing Sex-Specific Circadian, Metabolic, and Cognitive Phenotypes in the AβPP/PS1 and APPNL-F/NL-F Models of Alzheimer's Disease.

Background: Circadian disruption has long been recognized as a symptom of Alzheimer's disease (AD); however, emerging data suggests that circadian dysfunction occurs early on in disease development, potentially preceding any noticeable cognitive deficits.

Objective: This study compares the onset of AD in male and female wild type (C57BL6/J), transgenic (AβPP/PS1), and knock-in (APPNL-F/NL-F) AD mouse models from the period of plaque initiation (6 months) through 12 months.

Methods: Rhythmic daily activity patterns, glucose sensitivity, cognitive function (Morris water maze, MWM), and AD pathology (plaques formation) were assessed.

Growth Hormone Signaling Shapes the Impact of Environmental Temperature on Transcriptomic Profile of Different Adipose Tissue Depots in Male Mice.

Growth hormone receptor knockout (GHRKO) mice are smaller, long living, and have an increased metabolic rate compared with normal (N) littermates. However, it is known that thermoneutral conditions (30-32°C) elicit metabolic adaptations in mice, increasing the metabolic rate. Therefore, we hypothesized that environmental temperature would affect the expression profile of different adipose tissue depots in GHRKO mice.

Growth Hormone and Aging: New Findings.

Complex relationships between growth hormone (GH) signaling and mammalian aging continue to attract attention of many investigators. Recent results include evidence that the impact of GH on genome maintenance (DNA damage and repair) is drastically different in normal as compared to cancer cells, consistent with GH promoting aging and cancer progression. Impact of GH on DNA methylation was studied as a possible mechanism linking actions of GH during early life to the trajectory of aging.

Energy Metabolism and Aging.

Aging is strongly related to energy metabolism, but the underlying processes and mechanisms are complex and incompletely understood. Restricting energy intake and reducing metabolic rate can slow the rate of aging and extend longevity, implying a reciprocal relationship between energy metabolism and life expectancy. However, increased energy expenditure has also been associated with improved health and longer life.