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1.
Article in English | MEDLINE | ID: mdl-38773314

ABSTRACT

Despite established sex differences in the prevalence and presentation of psychiatric disorders, little is known about the cellular and synaptic mechanisms that guide these differences under basal conditions. The proper function of the prefrontal cortex (PFC) is essential for the top-down regulation of motivated behaviors. The activity of the PFC is tightly controlled by parvalbumin-expressing interneurons (PV-INs), a key subpopulation of fast-spiking GABAergic cells that regulate cortical excitability through direct innervations onto the perisomatic regions of nearby pyramidal cells. Recent rodent studies have identified notable sex differences in PV-IN activity and adaptations to experiences such as binge drinking. Here, we investigated the cellular and molecular mechanisms that underlie sex-specific regulation of PFC PV-IN function. Using whole-cell patch-clamp electrophysiology and selective pharmacology, we report that PV-INs from female mice are more excitable than those from males. Moreover, we find that mGlu1 and mGlu5 metabotropic glutamate receptors regulate cell excitability, excitatory drive, and endocannabinoid signaling at PFC PV-INs in a sex-dependent manner. Genetic deletion of mGlu5 receptors from PV-expressing cells abrogates all sex differences observed in PV-IN membrane and synaptic physiology. Lastly, we report that female, but not male, PV-mGlu5-/- mice exhibit decreased voluntary drinking on an intermittent access schedule, which could be related to changes in ethanol's stimulant properties. Importantly, these studies identify mGlu1 and mGlu5 receptors as candidate signaling molecules involved in sex differences in PV-IN activity and behaviors relevant to alcohol use.

2.
bioRxiv ; 2024 Mar 16.
Article in English | MEDLINE | ID: mdl-38045379

ABSTRACT

Despite established sex differences in the prevalence and presentation of psychiatric disorders, little is known about the cellular and synaptic mechanisms that guide these differences under basal conditions. Proper function of the prefrontal cortex (PFC) is essential for the top-down regulation of motivated behaviors. Activity of the PFC is tightly controlled by parvalbumin-expressing interneurons (PV-INs), a key subpopulation of fast-spiking GABAergic cells that regulate cortical excitability through direct innervations onto the perisomatic regions of nearby pyramidal cells. Recent rodent studies have identified notable sex differences in PV-IN activity and adaptations to experiences such as binge drinking. Here, we investigated the cellular and molecular mechanisms that underlie sex-specific regulation of PFC PV-IN function. Using whole-cell patch clamp electrophysiology and selective pharmacology, we report that PV-INs from female mice are more excitable than those from males. Moreover, we find that mGlu1 and mGlu5 metabotropic glutamate receptors regulate cell excitability, excitatory drive, and endocannabinoid signaling at PFC PV-INs in a sex-dependent manner. Genetic deletion of mGlu5 receptors from PV-expressing cells abrogates all sex differences observed in PV-IN membrane and synaptic physiology. Lastly, we report that female, but not male, PV-mGlu5-/- mice exhibit decreased voluntary drinking on an intermittent access schedule, which could be related to changes in ethanol's stimulant properties. Importantly, these studies identify mGlu1 and mGlu5 receptors as candidate signaling molecules involved in sex differences in PV-IN activity and behaviors relevant for alcohol use.

3.
Drug Alcohol Depend ; 251: 110921, 2023 Oct 01.
Article in English | MEDLINE | ID: mdl-37604013

ABSTRACT

Caffeinated alcoholic beverages (CABs) are widely consumed despite little known about their behavioral and biological effects. Furthermore, CABs are also popular among adolescents, a particularly vulnerable and maturing demographic. In this preliminary study, we compared levels of daily adolescent voluntary consumption of caffeine (0.03%), alcohol (10%), caffeinated alcohol (0.03% + 10%), or vehicle and evaluated the effects of this on mRNA expression in brain regions associated with addiction and known to be affected by each drug. Beginning on postnatal day 30, rats were allowed unrestricted access to gelatin combined with one, both, or neither drug for twenty days. Compared to vehicle-consuming animals, consumption of gelatin was significantly attenuated when alcohol was included. The addition of caffeine to alcohol increased alcohol consumption in the early days of access compared to alcohol alone; however, after two weeks, alcohol consumption between these groups reached comparable levels. Compared to animals consuming caffeine alone, combining caffeine with alcohol significantly reduced caffeine intake. Targeted mRNA analysis of tissue collected from the nucleus accumbens and orbitofrontal cortex after the consumption period identified unique patterns of differentially expressed genes between treatment groups, across a broad array of neurotransmitter systems. Of particular note were genes related to a number of solute transporters and serotonergic functions. This preliminary work suggests unique pharmacological and behavioral effects from consuming caffeinated alcohol during adolescence. Since CABs are widely consumed by adolescents, these results suggest that more research into the pharmacological and behavioral effects elicited by CABs is warranted.

4.
Sci Rep ; 13(1): 11198, 2023 07 11.
Article in English | MEDLINE | ID: mdl-37433844

ABSTRACT

There is agreement that high-LET radiation has a high Relative Biological Effectiveness (RBE) when delivered as a single treatment, but how it interacts with radiations of different qualities, such as X-rays, is less clear. We sought to clarify these effects by quantifying and modelling responses to X-ray and alpha particle combinations. Cells were exposed to X-rays, alpha particles, or combinations, with different doses and temporal separations. DNA damage was assessed by 53BP1 immunofluorescence, and radiosensitivity assessed using the clonogenic assay. Mechanistic models were then applied to understand trends in repair and survival. 53BP1 foci yields were significantly reduced in alpha particle exposures compared to X-rays, but these foci were slow to repair. Although alpha particles alone showed no inter-track interactions, substantial interactions were seen between X-rays and alpha particles. Mechanistic modelling suggested that sublethal damage (SLD) repair was independent of radiation quality, but that alpha particles generated substantially more sublethal damage than a similar dose of X-rays, [Formula: see text]. This high RBE may lead to unexpected synergies for combinations of different radiation qualities which must be taken into account in treatment design, and the rapid repair of this damage may impact on mechanistic modelling of radiation responses to high LETs.


Subject(s)
Alpha Particles , Radiation, Ionizing , Biological Assay , DNA Damage , Radiation Tolerance
5.
Neuropharmacology ; 238: 109638, 2023 11 01.
Article in English | MEDLINE | ID: mdl-37482180

ABSTRACT

The prefrontal cortex (PFC) regulates drinking behaviors and affective changes following chronic alcohol use. PFC activity is dynamically modulated by local inhibitory interneurons (INs), which can be divided into non-overlapping groups with distinct functional roles. Within deeper layers of neocortex, INs that express either parvalbumin or somatostatin directly inhibit pyramidal cells. By contrast, the plurality of all remaining INs express vasoactive intestinal peptide (VIP), reside within superficial layers, and preferentially target other types of INs. While recent studies have described adaptations to PFC parvalbumin-INs and somatostatin-INs in alcohol use models, whether ethanol or drinking affect the physiology of PFC VIP-INs has not been reported. To address this gap, we used genetically engineered female and male mice to target VIP-INs in layers 1-3 of prelimbic PFC for whole-cell patch-clamp electrophysiology. We found that ethanol (20 mM, ∼0.09 BEC/90 mg/dL) application to PFC brain slices enhances VIP-IN excitability. We next examined effects following chronic drinking by providing mice with 4 weeks of intermittent access (IA) ethanol two-bottle choice in the home cage. In these studies, VIP-INs from female and male IA ethanol mice displayed reduced excitability relative to cells from water-only controls. Finally, we assessed whether these effects continue into abstinence. After 7-13 days without ethanol, the hypo-excitability of VIP-INs from male IA ethanol mice persisted, whereas cells from female IA ethanol mice were not different from their controls. Together, these findings illustrate that acute ethanol enhances VIP-IN excitability and suggest these cells undergo pronounced homeostatic changes following long-term drinking.


Subject(s)
Neocortex , Vasoactive Intestinal Peptide , Mice , Male , Female , Animals , Vasoactive Intestinal Peptide/pharmacology , Vasoactive Intestinal Peptide/metabolism , Parvalbumins , Action Potentials , Interneurons/physiology , Ethanol/pharmacology , Prefrontal Cortex , Neocortex/metabolism , Somatostatin/pharmacology , Somatostatin/metabolism
6.
bioRxiv ; 2023 Mar 10.
Article in English | MEDLINE | ID: mdl-36945582

ABSTRACT

The prefrontal cortex (PFC) regulates drinking behaviors and affective changes following chronic alcohol use. PFC activity is dynamically modulated by local inhibitory interneurons (INs), which can be divided into non-overlapping groups with distinct functional roles. Within deeper layers of neocortex, INs that express either parvalbumin or somatostatin directly inhibit pyramidal cells. By contrast, the plurality of all remaining INs express vasoactive intestinal peptide (VIP), reside within superficial layers, and preferentially target other types of INs. While recent studies have described adaptations to PFC parvalbumin-INs and somatostatin-INs in alcohol use models, whether ethanol or drinking affect the physiology of PFC VIP-INs has not been reported. To address this gap, we used genetically engineered female and male mice to target VIP-INs in layers 1-3 of prelimbic PFC for whole-cell patch-clamp electrophysiology. We found that ethanol (20 mM, ∻0.09 BEC) application to PFC brain slices enhances VIP-IN excitability. We next examined effects following chronic drinking by providing mice with 4 weeks of intermittent access (IA) ethanol two-bottle choice in the home cage. In these studies, VIP-INs from female and male IA ethanol mice displayed reduced excitability relative to cells from water-only controls. Finally, we assessed whether these effects continue into abstinence. After 7-11 days without ethanol, the hypo-excitability of VIP-INs from male IA ethanol mice persisted, whereas cells from female IA ethanol mice were not different from their controls. Together, these findings illustrate that acute ethanol enhances VIP-IN excitability and suggest these cells undergo pronounced homeostatic changes following long-term drinking.

7.
Phys Med Biol ; 68(5)2023 02 20.
Article in English | MEDLINE | ID: mdl-36731135

ABSTRACT

Objective. Laser-accelerated protons offer an alternative delivery mechanism for proton therapy. This technique delivers dose-rates of ≥109Gy s-1, many orders of magnitude greater than used clinically. Such ultra-high dose-rates reduce delivery time to nanoseconds, equivalent to the lifetime of reactive chemical species within a biological medium. This leads to the possibility of inter-track interactions between successive protons within a pulse, potentially altering the yields of damaging radicals if they are in sufficient spatial proximity. This work investigates the temporal evolution of chemical species for a range of proton energies and doses to quantify the circumstances required for inter-track interactions, and determine any relevance within ultra-high dose-rate proton therapy.Approach. The TOPAS-nBio Monte Carlo toolkit was used to investigate possible inter-track interactions. Firstly, protons between 0.5 and 100 MeV were simulated to record the radial track dimensions throughout the chemical stage from 1 ps to 1µs. Using the track areas, the geometric probability of track overlap was calculated for various exposures and timescales. A sample of irradiations were then simulated in detail to compare any change in chemical yields for independently and instantaneously delivered tracks, and validate the analytic model.Main results. Track overlap for a clinical 2 Gy dose was negligible for biologically relevant timepoints for all energies. Overlap probability increased with time after irradiation, proton energy and dose, with a minimum 23 Gy dose required before significant track overlap occurred. Simulating chemical interactions confirmed these results with no change in radical yields seen up to 8 Gy for independently and instantaneously delivered tracks.Significance. These observations suggest that the spatial separation between incident protons is too large for physico-chemical inter-track interactions, regardless of the delivery time, indicating such interactions would not play a role in any potential changes in biological response between laser-accelerated and conventional proton therapy.


Subject(s)
Proton Therapy , Proton Therapy/methods , Protons , Monte Carlo Method
8.
J Nurs Adm ; 52(4): 222-227, 2022 Apr 01.
Article in English | MEDLINE | ID: mdl-35348487

ABSTRACT

Workplace violence, including verbal and physical abuse, is escalating nationwide. As healthcare workers try to enforce COVID-19 prevention policies and practices, this phenomenon is exacerbated. De-escalation training is a method to prepare nurses through increased situational awareness, leading to early recognition and improved coping and confidence in dealing with aggression. Outcomes are presented, suggesting education of nurses may have a positive influence on the number of security calls and incident reports.


Subject(s)
COVID-19 , Workplace Violence , Adaptation, Psychological , Aggression , COVID-19/prevention & control , Health Personnel , Humans , Workplace Violence/prevention & control
9.
Cancers (Basel) ; 14(3)2022 Jan 18.
Article in English | MEDLINE | ID: mdl-35158731

ABSTRACT

A wide range of Monte Carlo models have been applied to predict yields of DNA damage based on nanoscale track structure calculations. While often similar on the macroscopic scale, these models frequently employ different assumptions which lead to significant differences in nanoscale dose deposition. However, the impact of these differences on key biological readouts remains unclear. A major challenge in this area is the lack of robust datasets which can be used to benchmark models, due to a lack of resolution at the base pair level required to deeply test nanoscale dose deposition. Studies investigating the distribution of strand breakage in short DNA strands following the decay of incorporated 125I offer one of the few benchmarks for model predictions on this scale. In this work, we have used TOPAS-nBio to evaluate the performance of three Geant4-DNA physics models at predicting the distribution and yield of strand breaks in this irradiation scenario. For each model, energy and OH radical distributions were simulated and used to generate predictions of strand breakage, varying energy thresholds for strand breakage and OH interaction rates to fit to the experimental data. All three models could fit well to the observed data, although the best-fitting strand break energy thresholds ranged from 29.5 to 32.5 eV, significantly higher than previous studies. However, despite well describing the resulting DNA fragment distribution, these fit models differed significantly with other endpoints, such as the total yield of breaks, which varied by 70%. Limitations in the underlying data due to inherent normalisation mean it is not possible to distinguish clearly between the models in terms of total yield. This suggests that, while these physics models can effectively fit some biological data, they may not always generalise in the same way to other endpoints, requiring caution in their extrapolation to new systems and the use of multiple different data sources for robust model benchmarking.

10.
Med J (Ft Sam Houst Tex) ; (PB 8-21-04/05/06): 38-43, 2021.
Article in English | MEDLINE | ID: mdl-34251663

ABSTRACT

INTRODUCTION: Retrobulbar hemorrhage (RBH) occurs in only 0.45% of ocular trauma, but failure to provide timely lateral canthotomy and cantholysis (LCC) risks permanent visual deficits. With ocular trauma rates as high as 8.5-10% amongst modern combat injuries, and more than 2,000 severe eye injuries documented over a 10 year span, this concern increases.12-15 However, given infrequent RBH occurrence in the non-combat environment, emergency medicine residents trained in stateside settings may not receive adequate LCC exposure prior to military deployment. Simulators should be evaluated for procedural confidence compared to expensive and cumbersome traditional live tissue training (LTT) options. We seek to compare procedural confidence and usability of emergency medicine military residents performing LCC on a novel simulator to those using LTT. METHODS: This study randomized 32 emergency physician and physician assistant residents to perform LCC on a simulator or LTT model. All received a standardized brief on RBH recognition and LCC, then completed an 11-question survey using a 100-mm visual numerical rating scale about their ability to correctly identify RBH and perform LCC. The survey was repeated after LCC completion. All volunteers additionally completed a 10-question survey utilizing a 5-point Likert scale on the usability of the model to which they were randomized. RESULTS: No significant difference in reported confidence changes between groups was found; however, significant increases were found across all reported confidence measures between pre- and post-trainer use in the overall sample population. LCC simulator users reported significantly higher usability in 7 of 10 ratings. CONCLUSION: The lack of a statistically significant difference between groups in procedural confidence suggests artificial LCC simulators may offer an attractive alternative to logistically-complicated porcine models. Further research is needed to evaluate non-inferiority and procedural performance.


Subject(s)
Emergency Medicine , Eye Injuries , Military Medicine , Retrobulbar Hemorrhage , Animals , Eyelids , Humans , Swine
11.
Genes Brain Behav ; 20(1): e12652, 2021 01.
Article in English | MEDLINE | ID: mdl-32144885

ABSTRACT

A common feature associated with fetal alcohol spectrum disorders is the inability to concentrate on a specific task while ignoring distractions. Human continuous performance tasks (CPT), measure vigilance and cognitive control simultaneously while these processes are traditionally measured separately in rodents. We recently established a touchscreen 5-choice CPT (5C-CPT) that measures vigilance and cognitive control simultaneously by incorporating both target and nontargets and showed it was sensitive to amphetamine-induced improvement in humans and mice. Here, we examined the effects of moderate prenatal alcohol exposure (PAE) in male and female mice on performance of the 5-choice serial reaction time task (5-CSRTT), which contained only target trials, and the 5C-CPT which incorporated both target and nontarget trials. In addition, we assessed gait and fine motor coordination in behavioral naïve PAE and control animals. We found that on the 5-CSRTT mice were able to respond to target presentations with similar hit rates regardless of sex or treatment. However, on the 5C-CPT PAE mice made significantly more false alarm responses vs controls. Compared with control animals, PAE mice had a significantly lower sensitivity index, a measure of ability to discriminate appropriate responses to stimuli types. During 5C-CPT, female mice, regardless of treatment, also had increased mean latency to respond when correct and omitted more target trials. Gait assessment showed no significant differences in PAE and SAC mice on any measure. These findings suggest that moderate exposure to alcohol during development can have long lasting effects on cognitive control unaffected by gross motor alterations.


Subject(s)
Attention , Cognition , Fetal Alcohol Spectrum Disorders/physiopathology , Animals , Choice Behavior , Female , Gait , Male , Mice , Mice, Inbred C57BL , Motor Skills
12.
J Interpers Violence ; 36(5-6): 2353-2372, 2021 03.
Article in English | MEDLINE | ID: mdl-29502502

ABSTRACT

The risk of harm/injury in homes where intimate partner violence (IPV) occurs is not limited to humans; animals reside in as many as 80% of these homes and may be at substantial risk of suffering severe or fatal injury. Gaining a better understanding of IPV-pet abuse overlap is imperative in more accurately identifying the risks of harm for all individuals and animals residing in these homes. The objectives of this study were to utilize law enforcement officers' observations and IPV victim reports from the scene of the incident to (a) determine the prevalence of pet abuse perpetration among suspects involved in IPV incidents, (b) compare characteristics of IPV incidents and the home environments in which they occur when the suspect has a history of pet abuse with incidents involving suspects with no reported history of pet abuse, and (c) compare IPV incident outcomes involving suspects with a history of pet abuse with those involving suspects with no reported history of pet abuse. IPV victims residing in homes with a suspect who has a history of pet abuse often describe "extremely high-risk" environments. With nearly 80% reporting concern that they will eventually be killed by the suspect, victims in these environments should be considered at significant risk of suffering serious injury or death. In addition, IPV victims involved in incidents with a suspect that has a history of pet abuse were significantly more likely to have had at least one prior unreported IPV incident with the suspect (80%) and to have ever been strangled (76%) or forced to have sex with the suspect (26%). Effective prevention/detection/intervention strategies are likely to require multidisciplinary collaboration and safety plans that address the susbstantial risk of harm/injury for all adults, children, and animals residing in the home.


Subject(s)
Child Abuse , Intimate Partner Violence , Adult , Animals , Child , Humans , Law Enforcement , Police , Prevalence
14.
Behav Brain Res ; 380: 112449, 2020 02 17.
Article in English | MEDLINE | ID: mdl-31870780

ABSTRACT

Alcohol use disorder is pervasive and effects the health of millions. Identifying factors such as early life stress that contribute to the development of alcohol use disorder is therefore critical, especially those that contribute to adolescent drinking, a strong predictor of AUD development. The majority of prior studies have examined early life effects on adult drinking, but have not studied intake during adolescence, and no prior studies have examined how the effects of multiple stressors may be additive. Therefore, this study determined if experiencing individual or multiple stressors increases adolescent alcohol intake. Male Long Evans rats underwent either early or late maternal separation (postnatal day 2-9 or 13-20), early adolescent social defeat (PND 30-40), both, or neither. All rats were then given two-hour access to alcohol, and voluntary intake assessed daily in late adolescence (PND 41-51). In adulthood, sensitivity to alcohol's sedative effects was assessed using loss and regain of righting reflex tests. Results indicate that experiencing maternal separation (at either time point) or social defeat increased adolescent alcohol consumption, but experiencing the combined stressors did not, and that no stressor significantly affected body weight during adolescence or loss and regain of righting reflex in adulthood. Overall, this pattern of effects suggests that experiencing any individual early life stressor may increase adolescent alcohol intake, in agreement with prior literature, but that the combined effects of multiple early life stressors may be more complicated.


Subject(s)
Alcohol Drinking/physiopathology , Alcoholism/etiology , Behavior, Animal/physiology , Maternal Deprivation , Social Defeat , Stress, Psychological/complications , Age Factors , Animals , Disease Models, Animal , Male , Rats , Rats, Long-Evans
15.
Neurosci Lett ; 718: 134700, 2020 01 23.
Article in English | MEDLINE | ID: mdl-31874217

ABSTRACT

Prenatal alcohol exposure (PAE) negatively impacts hippocampal development and impairs hippocampal-sensitive learning and memory. However, hippocampal neural adaptations in response to moderate PAE are not completely understood. To explore the effects of moderate PAE on GABAergic interneuron expression, this study used a rat model of moderate PAE to examine the effects of PAE on parvalbumin (PARV)-positive cells in fields CA1, CA3 and the dentate gyrus (DG) of the dorsal hippocampus (dHC). Long-Evans dams were given daily access to 5 % (vol/vol) ethanol or saccharine (SAC) control solutions throughout the course of gestation. Offspring were divided into four separate groups: PAE (n = 7) or SAC (n = 7) males, or PAE (n = 8) or SAC (n = 8) females. All rats were aged to adulthood and, following testing in the Morris water task, their brains were analyzed for the expression of the GABAergic neuronal marker PARV. We report a main effect of PAE on GABAergic expression, with significant reductions in PARV-positive cells in area CA3 for males and the DG for females. There was also a trend for a reduction in PARV expressing neurons in fields CA1 and CA3 in females. The results are discussed in relation to hippocampal GABAergic interneuron function, PAE and behavior.


Subject(s)
Ethanol/pharmacology , GABAergic Neurons/metabolism , Hippocampus/metabolism , Interneurons/drug effects , Parvalbumins/metabolism , Prenatal Exposure Delayed Effects , Aging , Animals , Dentate Gyrus/drug effects , Female , Hippocampus/drug effects , Hippocampus/pathology , Interneurons/metabolism , Male , Pregnancy , Prenatal Exposure Delayed Effects/metabolism , Rats, Long-Evans
16.
J Interpers Violence ; 35(13-14): 2583-2606, 2020 07.
Article in English | MEDLINE | ID: mdl-29294722

ABSTRACT

The objectives of this study were to identify intimate partner violence (IPV) incidence rates, to quantify specific risks and characteristics of these incidents and the environments in which they occur, to identify how often children are present for or injured during these incidents, and to identify differences in victim reports of IPV to law enforcement officers at the scene of the incident compared with previously published reports of IPV from retropsective, anonymous surveys and domestic violence shelter interviews. Data gathered by responding law enforcement officers at the scene of the IPV incident were used to determine the prevalence of IPV incident characteristics and outcomes. Females aged 20 to 39 years, unmarried adults, and African Americans were disproportionately represented as victims of IPV in this study. IPV incidents were significantly more likely to occur on Saturdays and Sundays and during the months of May through August. Relationship durations for suspect-victim pairs were most often less than 12 months at the time of the incident. Weapon use and/or strangulation was common, occurring in 44% of all incidents. Minors (under age 18 years) were frequently present in the home during the IPV incident or a member of the household (59%). This study provides a unique perspective of IPV by utilizing data collected directly from the scene of the incident by first responders. Previously published characteristics of IPV were confirmed, but this study also brings to light new and critical information concerning this prevalent form of violence. Study findings relating to incidence, seasonality, severity, disproportionately affected populations, and child exposure are discussed.


Subject(s)
Domestic Violence , Exposure to Violence , Intimate Partner Violence/statistics & numerical data , Police , Adolescent , Adult , Child , Exposure to Violence/statistics & numerical data , Family Characteristics , Female , Humans , Incidence , Indiana/epidemiology , Law Enforcement , Prevalence , Young Adult
17.
Sci Rep ; 8(1): 16153, 2018 11 01.
Article in English | MEDLINE | ID: mdl-30385825

ABSTRACT

Spatial navigation is impaired in early stages of Alzheimer's disease, and may be a defining behavioral marker of preclinical AD. A new rat model (TgF344-AD) of AD overcomes many limitations of other rodent models, though spatial navigation has not been comprehensively assessed. Using the hidden and cued platform variants of the Morris water task, a longitudinal assessment of spatial navigation was conducted on TgF344-AD (n = 16) and Fischer 344 (n = 12) male and female rats at three age ranges: 4 to 5 months, 7 to 8, and 10 to 11 months of age. TgF344-AD rats exhibited largely intact navigation at 4-5 months, with deficits in the hidden platform task emerging at 7-8 months and becoming significantly pronounced at 10-11 months of age. In general, TgF344-AD rats displayed less accurate swim trajectories to the platform and searched a wider area around the platform region compared to wildtype rats. Impaired navigation occurred in the absence of deficits in acquiring the procedural task demands or navigation to the cued platform location. Together, the results indicate that TgF344-AD rats exhibit comparable navigational deficits to those found in individuals with preclinical-AD.


Subject(s)
Alzheimer Disease/physiopathology , Spatial Navigation/physiology , Animals , Disease Models, Animal , Female , Humans , Male , Maze Learning/physiology , Rats , Rats, Inbred F344 , Water
18.
Learn Motiv ; 61: 3-15, 2018 Feb.
Article in English | MEDLINE | ID: mdl-30270939

ABSTRACT

Animals occupy territories in which resources such as food and shelter are often distributed unevenly. While studies of exploratory behavior have typically involved the laboratory rodent as an experimental subject, questions regarding what constitutes exploration have dominated. A recent line of research has utilized a descriptive approach to the study of rodent exploration, which has revealed that this behavior is organized into movement subsystems that can be readily quantified. The movements include home base behavior, which serves as a central point of attraction from which rats and mice organize exploratory trips into the remaining environment. In this review, we describe some of the features of this organized behavior pattern as well as its modulation by sensory cues and previous experience. We conclude the review by summarizing research investigating the neurobiological bases of exploration, which we hope will stimulate renewed interest and research on the neural systems mediating rodent exploratory behavior.

19.
Neurobiol Aging ; 61: 169-176, 2018 01.
Article in English | MEDLINE | ID: mdl-29107184

ABSTRACT

Alzheimer's disease (AD) is characterized by progressive cognitive decline and the presence of aggregates of amyloid beta (plaques) and hyperphosphorylated tau (tangles). Early diagnosis through neuropsychological testing is difficult due to comorbidity of symptoms between AD and other types of dementia. As a result, there is a need to identify the range of behavioral phenotypes expressed in AD. In the present study, we utilized a transgenic rat (TgF344-AD) model that bears the mutated amyloid precursor protein as well as presenilin-1 genes, resulting in progressive plaque and tangle pathogenesis throughout the cortex. We tested young adult male and female TgF344-AD rats in a spatial memory task in the Morris water maze and for anxiety-like behavior in the elevated plus-maze. Results indicated that regardless of sex, TgF344-AD rats exhibited increased anxiety-like behavior in the elevated plus-maze, which occurred without significant deficits in the spatial memory. Together, these results indicate that enhanced anxiety-like behavior represents an early-stage behavioral marker in the TgF344-AD rat model.


Subject(s)
Alzheimer Disease/diagnosis , Alzheimer Disease/psychology , Anxiety , Endophenotypes , Animals , Disease Models, Animal , Female , Male , Maze Learning , Memory , Rats, Transgenic , Spatial Behavior
20.
Mil Med ; 182(5): e1803-e1806, 2017 05.
Article in English | MEDLINE | ID: mdl-29087928

ABSTRACT

BACKGROUND: Although lightning strikes are a rare occurrence, their significance cannot be ignored given military operations in the field during all types of weather. With proper medical management, patients with lightning injuries can return to duty. METHODS: Information for this case report comes from eyewitness account at the 6th Ranger Training Battalion and from review of physician documentation from the 96th Medical Group, Eglin Air Force Base, Florida. RESULTS: A lightning strike injured 44 Ranger School participants during a training exercise on August 12, 2015, at Camp Rudder, Florida. These patients were triaged in the field and transported to emergency department of Eglin Air Force Base. Of the 44 casualties, 20 were admitted. All were returned to duty the following day. One patient had cardiac arrest. This patient, along with two others, was admitted to the intensive care unit. Seventeen other patients were admitted for observation for rhabdomyolysis and/or cardiac arrhythmias. One patient was admitted with suspected acute kidney injury indicated by an elevated creatinine. All patients, including those admitted to the intensive care unit, were released on the day following the lightning strike without restrictions and were allowed to return to duty with increased medical monitoring. DISCUSSION: This case report highlights the need for proper triage and recognition of lightning strike injury, coordination of care between field operations and emergency department personnel, and close follow-up for patients presenting with lightning injury. Symptoms, physical exam, and laboratory findings from rigorous training can be difficult to distinguish from those resulting from lightning injury. Secondary injuries resulting from blunt trauma from falls may have been prevented by the use of the lightning strike posture. Further analysis of procedures and standard operating protocols to mitigate risk during thunderstorms may be required to prevent lightning's effects on large groups of military personnel.


Subject(s)
Education/trends , Lightning Injuries/complications , Mass Casualty Incidents/statistics & numerical data , Military Personnel/statistics & numerical data , Adult , Bradycardia/etiology , Florida/epidemiology , Heart Arrest/etiology , Humans , Hypertension/etiology , Lightning Injuries/epidemiology , Male , Paralysis/etiology , Unconsciousness/etiology
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