Publications by authors named "Karen L Gamble"

Article Synopsis
  • Parkinson's disease (PD) and Dementia with Lewy bodies (DLB) feature harmful protein aggregates called Lewy Pathology, notably in the basolateral amygdala, which affects cognition and emotional processing.
  • Research using C57BL/6 J mice injected with α-syn pre-formed fibrils (PFFs) indicates that while synapse loss is minimal, the structure of excitatory synapses in the amygdala changes significantly post-aggregation, increasing their size and volume.
  • Additionally, findings suggest that pathological α-syn influences synaptic functioning by altering distances between synaptic vesicles, indicating a link between protein aggregation and synaptic transmission issues.
View Article and Find Full Text PDF
Article Synopsis
  • Parkinson's disease and Dementia with Lewy bodies are linked to the presence of α-synuclein aggregates in the brain, especially in the basolateral amygdala (BLA), which is important for cognition and emotional response.
  • In a mouse model, injecting pre-formed α-synuclein fibrils into the brain led to aggregation in the BLA and resulted in impaired contextual fear conditioning and changes in excitatory synaptic transmission.
  • The study found that while α-synuclein aggregates did not significantly reduce the number of synapses in the BLA, they altered the morphology of synapses and increased their volume, suggesting significant synaptic architecture changes due to pathologic α-synuclein. *
View Article and Find Full Text PDF

The central circadian regulator within the suprachiasmatic nucleus transmits time of day information by a diurnal spiking rhythm driven by molecular clock genes controlling membrane excitability. Most brain regions, including the hippocampus, harbor similar intrinsic circadian transcriptional machinery, but whether these molecular programs generate oscillations of membrane properties is unclear. Here, we show that intrinsic excitability of mouse dentate granule neurons exhibits a 24-h oscillation that controls spiking probability.

View Article and Find Full Text PDF
Article Synopsis
  • Timing when we eat is really important for staying healthy, especially for people who have obesity.
  • A new study with mice shows that the body's internal clock, especially in fat cells, can affect how we metabolize food.
  • Eating high-fat foods at the right time can help with burning energy better and staying healthier.
View Article and Find Full Text PDF

Healthy individuals exhibit blood pressure variation over a 24-hour period with higher blood pressure during wakefulness and lower blood pressure during sleep. Loss or disruption of the blood pressure circadian rhythm has been linked to adverse health outcomes, for example, cardiovascular disease, dementia, and chronic kidney disease. However, the current diagnostic and therapeutic approaches lack sufficient attention to the circadian rhythmicity of blood pressure.

View Article and Find Full Text PDF

Circadian rhythms are biological processes that cycle across 24 h and regulate many facets of neurophysiology, including learning and memory. Circadian variation in spatial memory task performance is well documented; however, the effect of sex across circadian time (CT) remains unclear. Additionally, little is known regarding the impact of time-of-day on hippocampal neuronal physiology.

View Article and Find Full Text PDF

Insomnia is a common sleep disorder associated with poor health outcomes. Individuals from racially underrepresented groups as well as women tend to report more severe insomnia symptoms, and frequent experiences of discrimination have been found to drive such disparities. Smokers commonly experience sleep problems since nicotine can alter the sleep-wake cycle.

View Article and Find Full Text PDF

Background: Circadian misalignment between behaviors such as feeding and endogenous circadian rhythms, particularly in the context of shiftwork, is associated with poorer cardiometabolic health. We examined whether insulin and leptin levels differ between dayshift versus nightshift nurses, as well as explored whether the timing of food intake modulates these effects in nightshift workers.

Methods: Female nurses (N=18; 8 dayshift and 10 nightshift) completed daily diet records for 8 consecutive days.

View Article and Find Full Text PDF

Age-related cognitive decline and disruptions in circadian rhythms are growing problems as the average human life span increases. Multiple strains of the senescence-accelerated mouse (SAM) show reduced life span, and the SAMP8 strain in particular has been well documented to show cognitive deficits in behavior as well as a bimodal pattern of circadian locomotor activity. However, little is known about circadian regulation within the hippocampus of these strains of mice.

View Article and Find Full Text PDF

Night shift work increases risk of cardiovascular disease associated with an irregular eating schedule. Elevating this risk is the high level of salt intake observed in the typical Western diet. Renal Na excretion has a distinct diurnal pattern, independent of time of intake, yet the interactions between the time of intake and the amount of salt ingested are not clear.

View Article and Find Full Text PDF

Aims/hypothesis: Hypothalamic inflammation and sympathetic nervous system hyperactivity are hallmark features of the metabolic syndrome and type 2 diabetes. Hypothalamic inflammation may aggravate metabolic and immunological pathologies due to extensive sympathetic activation of peripheral tissues. Loss of somatostatinergic (SST) neurons may contribute to enhanced hypothalamic inflammation.

View Article and Find Full Text PDF
Article Synopsis
  • Alzheimer's patients experience disrupted sleep/wake cycles and circadian rhythms, which may affect brain function, particularly in the hippocampus.
  • Research on Tg-SwDI mice, which have genetic mutations related to human Alzheimer's, shows they exhibit no day/night differences in spatial memory performance, differing from control mice that perform better at night.
  • The Tg-SwDI mice also demonstrate impairments in hippocampal neurophysiology, including altered excitability and synaptic activity, indicating that disruptions in circadian clock gene expression may contribute to cognitive decline.
View Article and Find Full Text PDF

Feeding rodents a high-fat diet (HFD) disrupts normal behavioral rhythms, particularly meal timing. Within the brain, mistimed feeding shifts molecular rhythms in the hippocampus and impairs memory. We hypothesize that altered meal timing induced by an HFD leads to cognitive impairment and that restricting HFD access to the "active period" (i.

View Article and Find Full Text PDF

Background: Diurnal variation of natriuretic peptide (NP) levels and its relationship with 24-h blood pressure (BP) rhythm has not been established. Obese individuals have a relative NP deficiency and disturbed BP rhythmicity.

Objectives: This clinical trial evaluated the diurnal rhythmicity of NPs (B-type natriuretic peptide [BNP], mid-regional pro-atrial natriuretic peptide [MR-proANP], N-terminal pro-B-type natriuretic peptide [NT-proBNP]) and the relationship of NP rhythm with 24-h BP rhythm in healthy lean and obese individuals.

View Article and Find Full Text PDF

This White Paper presents the results from a workshop cosponsored by the Sleep Research Society (SRS) and the Society for Research on Biological Rhythms (SRBR) whose goals were to bring together sleep clinicians and sleep and circadian rhythm researchers to identify existing gaps in diagnosis and treatment and areas of high-priority research in circadian rhythm sleep-wake disorders (CRSWD). CRSWD are a distinct class of sleep disorders caused by alterations of the circadian time-keeping system, its entrainment mechanisms, or a misalignment of the endogenous circadian rhythm and the external environment. In these disorders, the timing of the primary sleep episode is either earlier or later than desired, irregular from day-to-day, and/or sleep occurs at the wrong circadian time.

View Article and Find Full Text PDF

Timing of food intake has become a critical factor in determining overall cardiometabolic health. We hypothesized that timing of food intake entrains circadian rhythms of blood pressure (BP) and renal excretion in mice. Male C57BL/6J mice were fed ad libitum or reverse feeding (RF) where food was available at all times of day or only available during the 12-h lights-on period, respectively.

View Article and Find Full Text PDF

Glucagon regulates glucose and lipid metabolism and promotes weight loss. Thus, therapeutics stimulating glucagon receptor (GCGR) signaling are promising for obesity treatment; however, the underlying mechanism(s) have yet to be fully elucidated. We previously identified that hepatic GCGR signaling increases circulating fibroblast growth factor 21 (FGF21), a potent regulator of energy balance.

View Article and Find Full Text PDF

Objective: This study aimed to investigate both the long-term and short-term impacts of high-fat diets (HFD) or high-sucrose diets (HSD) on the normal diurnal pattern of cognitive function, protein expression, and the molecular clock in mice.

Methods: This study used both 6-month and 4-week feeding strategies by providing male C57BL/6J mice access to either a standard chow, HFD, or HSD. Spatial working memory and synaptic plasticity were assessed both day and night, and hippocampal tissue was measured for changes in NMDA and AMPA receptor subunits (GluN2B, GluA1), as well as molecular clock gene expression.

View Article and Find Full Text PDF

Heavy alcohol drinking dysregulates lipid metabolism, promoting hepatic steatosis - the first stage of alcohol-related liver disease (ALD). The molecular circadian clock plays a major role in synchronizing daily rhythms in behavior and metabolism and clock disruption can cause pathology, including liver disease. Previous studies indicate that alcohol consumption alters liver clock function, but the impact alcohol or clock disruption, or both have on the temporal control of hepatic lipid metabolism and injury remains unclear.

View Article and Find Full Text PDF

Senescence-Accelerated Mouse-Prone 8 (SAMP8) mice exhibit characteristics of premature aging, including hair loss, cognitive dysfunction, reduced physical activity, impaired metabolic homeostasis, cardiac dysfunction and reduced lifespan. Interestingly, circadian disruption can induce or augment many of these same pathologies. Moreover, previous studies have reported that SAMP8 mice exhibit abnormalities in circadian wheel-running behavior, indicating possible alterations in circadian clock function.

View Article and Find Full Text PDF

Introduction: Treatment with positive airway pressure (PAP) therapy reduces injury risk among adults with obstructive sleep apnea syndrome (OSAS), but the effect of PAP therapy on children's injury risk is unknown. This study investigated whether treatment of OSAS with PAP reduces children's pedestrian injury risk in a virtual reality pedestrian environment.

Methods: Forty-two children ages 8-16 years with OSAS were enrolled upon diagnosis by polysomnography.

View Article and Find Full Text PDF

Circadian misalignment between sleep and behavioral/feeding rhythms is thought to lead to various health impairments in shift workers. Therefore, we investigated how shift work leads to genome-wide circadian dysregulation in hospital nurses. Female nurses from the University of Alabama at Birmingham (UAB) Hospital working night shift ( n = 9; 29.

View Article and Find Full Text PDF