A long-term obesogenic high-fat diet in mice partially dampens the anti-frailty benefits of late-life intermittent fasting.

The global obesity pandemic coupled with ever-growing life expectancies equates to hundreds of millions of individuals with potentially longer but not healthier lives. Aging is one of the risk factors for numerous maladies such as metabolic disorder and frailty, which are exacerbated under obesity. Thus, therapeutic approaches that address obesity to ultimately improve affected individuals' quality of life and extend their lifespan are needed.

Peripubertal Bisphenol A Exposure Imparts Detrimental Age-Related Changes in Body Composition, Cognition, and Hydrogen Sulfide Production Capacities.

Peripubertal endocrine disruption has immediate and lifelong consequences on health, cognition, and lifespan. Disruption comes from dietary, environmental, and pharmaceutical sources. The plasticizer Bisphenol A (BPA) is one such endocrine disrupting chemical.

Dietary restriction transforms the mammalian protein persulfidome in a tissue-specific and cystathionine γ-lyase-dependent manner.

Hydrogen sulfide (HS) is a cytoprotective redox-active metabolite that signals through protein persulfidation (R-SSH). Despite the known importance of persulfidation, tissue-specific persulfidome profiles and their associated functions are not well characterized, specifically under conditions and interventions known to modulate HS production. We hypothesize that dietary restriction (DR), which increases lifespan and can boost HS production, expands tissue-specific persulfidomes.

Late-life intermittent fasting decreases aging-related frailty and increases renal hydrogen sulfide production in a sexually dimorphic manner.

Global average life expectancy continues to rise. As aging increases the likelihood of frailty, which encompasses metabolic, musculoskeletal, and cognitive deficits, there is a need for effective anti-aging treatments. It is well established in model organisms that dietary restriction (DR), such as caloric restriction or protein restriction, enhances health and lifespan.

Sex-dependent effects of early life inflammatory pain on sucrose intake and sucrose-associated hippocampal Arc expression in adult rats.

We hypothesize that dorsal hippocampal (dHC) neurons, which are critical for episodic memory, form a memory of a meal and inhibit the initiation of the next meal and the amount ingested during that meal. In support, we showed previously that (1) consuming a sucrose meal induces expression of the synaptic plasticity marker activity-regulated cytoskeleton-associated protein (Arc) in dHC neurons and (2) reversible inactivation of these neurons immediately following a sucrose meal accelerates the onset of the next meal and increases the size of that meal. These data suggest that hippocampal-dependent memory inhibits intake; therefore, the following experiments were conducted to determine whether hippocampal-dependent memory impairments are associated with increased intake.

Sweet orosensation induces Arc expression in dorsal hippocampal CA1 neurons in an experience-dependent manner.

There is limited knowledge regarding how the brain controls the timing of meals. Similarly, there is a large gap in our understanding of how top-down cognitive processes, such as memory influence energy intake. We hypothesize that dorsal hippocampal (dHC) neurons, which are critical for episodic memory, form a memory of a meal and inhibit meal onset during the postprandial period.

Early life inflammatory pain induces long-lasting deficits in hippocampal-dependent spatial memory in male and female rats.

The present experiment tested the hypothesis that neonatal injury disrupts adult hippocampal functioning and that normal aging or chronic stress during adulthood, which are known to have a negative impact on hippocampal function, exacerbate these effects. Male and female Sprague-Dawley rats were given an intraplantar injection of the inflammatory agent carrageenan (1%) on the day of birth and their memory was tested in the hippocampal-dependent spatial water maze in adulthood and again in middle age. We found that neonatal injury impaired hippocampal-dependent memory in adulthood, that the effects of injury on memory were more pronounced in middle-aged male rats, and that chronic stress accelerated the onset of these memory deficits.

Remembering to eat: hippocampal regulation of meal onset.

A wide variety of species, including vertebrate and invertebrates, consume food in bouts (i.e., meals).

Hippocampal neurons inhibit meal onset.

There is extensive research regarding the neural mechanisms involved in satiety and meal termination; in contrast, there is very limited understanding of how meal onset is regulated. On the basis of several converging lines of evidence, we hypothesized that hippocampal neurons form a memory of a meal and inhibit meal onset during the postprandial period. As a first step, we tested whether reversible inactivation of the hippocampus with muscimol infusions after the end of one meal would accelerate the onset of the next meal.

An analysis of nicotine conditioned place conditioning in early postweanling and adolescent rats neonatally treated with quinpirole.

This study investigated nicotine place conditioning in early postweanling and adolescent male and female rats neonatally treated with quinpirole, a dopamine D(2)/D(3) agonist. Previous research has shown that neonatal quinpirole treatment results in an increase of dopamine D(2)-like receptor sensitivity that persists throughout the animal's lifetime, relevant to psychosis. Rats were neonatally treated with quinpirole or saline from postnatal day (P)1-21, and animals were conditioned with nicotine or saline daily from P23-30 as early postweanlings or P32-39 as adolescents in a two- or three-chambered place conditioning apparatus.