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Roux-en-Y gastric bypass surgery (RYGB) remains an effective weight-loss method used to treat obesity. While it is successful in combating obesity, there are many lingering questions related to the changes in the brain following RYGB surgery, one of them being its effects on neuroinflammation. While it is known that chronic high-fat diet (HFD) contributes to obesity and neuroinflammation, it remains to be understood whether bariatric surgery can ameliorate diet-induced inflammatory responses. To examine this, rats were assigned to either a normal diet (ND) or a HFD for 8 weeks. Rats fed a HFD were split into the following groups: sham surgery with ad libitum access to HFD (sham-HF); sham surgery with calorie-restricted HFD (sham-FR); RYGB surgery with ad libitum access to HFD (RYGB). Following sham or RYGB surgeries, rats were maintained on their diets for 9 weeks before being euthanized. [3 H] PK11195 autoradiography was then performed on fresh-frozen brain tissue in order to measure activated microglia. Sham-FR rats showed increased [3 H] PK11195 binding in the amygdala (63%), perirhinal (60%), and ectorhinal cortex (53%) compared with the ND rats. Obese rats who had the RYGB surgery did not show this increased inflammatory effect. Since the sham-FR and RYGB rats were fed the same amount of HFD, the surgery itself seems responsible for this attenuation in [3 H] PK11195 binding. We speculate that calorie restriction following obese conditions may be seen as a stressor and contribute to inflammation in the brain. Further research is needed to verify this mechanism.
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Derivação Gástrica , Ratos , Animais , Derivação Gástrica/métodos , Restrição Calórica , Doenças Neuroinflamatórias , Obesidade/cirurgiaRESUMO
INTRODUCTION: Nicotine and tobacco use remain high both globally and in the USA, contributing to large healthcare expenditures. With a rise in e-cigarette use, it is important to have clinically relevant models of inhaled nicotine exposure. This study aims to extend prior preclinical nicotine inhalation animal data to females and provide both behavior and serum pharmacokinetics. METHODS: We tested two inhalation doses of nicotine (24 mg/ml and 59 mg/ml) and compared these to injected doses (0.4 mg/kg and 1 mg/kg). In addition, we assessed locomotor behavior after the same doses. Blood was collected at 10- and 120-minutes post-administration. We assessed nicotine and cotinine serum concentrations by LC-MS/MS. RESULTS: showed that while nicotine serum concentrations for the respective high and low-dose administrations were similar between both routes of administration, the route had differential effects on locomotor behavior. Inhaled nicotine showed a dose-dependent decrease in locomotor activity while injected doses showed the opposite trend. CONCLUSIONS: Our results indicate that the route of administration is an important factor when establishing preclinical models of nicotine exposures. Given that the overall use of e-cigarettes in vulnerable populations is on the rise, our study provides important behavioral and pharmacokinetic information to advance our currently limited understanding of the effects of nicotine vapor exposure. IMPLICATIONS: This study highlights behavioral differences between different routes of administration of similar doses of nicotine. Using a low and high dose of nicotine, we found that nicotine serum concentrations were similar between the different routes of administration. Our results indicate that different routes of administration have opposing effects on locomotor activity. These findings provide important implications for future behavioral models.
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Dopamine is an important neuromodulator in the brain that binds to dopamine D1-like receptors (D1, D5) as well as dopamine D2-like receptors (D2, D3, D4). The D2 receptor is known to play an integral role in a variety of physiological processes including addictive behaviors, locomotion, motivation, feeding behavior, and more. It was recently reported that dopamine is a direct-acting modulator of mammalian GABA(A) receptors. To this end, we wanted to examine how the expression of the dopamine D2 gene impacts the expression of GABA(A) receptors in the brain under different dietary conditions. Adult female Drd2 wild-type (WT), heterozygous (HT), and knockout (KO) mice were given either normal or high-fat diet for a period of 30 weeks. Following this, their brains were collected for [3H] Flunitrazepam binding in order to assess GABA(A) receptor expression. A high fat diet significantly increased [3H] Flunitrazepam binding in the regions of the somatosensory cortex, striatum, and various other cortical areas within WT mice. In contrast, no effect of diet was observed in HT or KO mice. As such, HT and KO mice displayed reduced [3H] Flunitrazepam binding in these areas relative to WT mice under high-fat dietary conditions. The effect of a high-fat diet on [3H] Flunitrazepam binding is consistent with recent evidence showing increases in GABA neurotransmitter levels following a high-fat diet. We demonstrate for the first time that the expression of the D2 gene plays a prominent role in the ability of a high-fat diet to impact GABA(A) receptors in the mouse brain.
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Dieta Hiperlipídica , Receptores de Dopamina D1 , Animais , Encéfalo/metabolismo , Dopamina/metabolismo , Feminino , Flunitrazepam/metabolismo , Mamíferos/metabolismo , Camundongos , Camundongos Knockout , Neurotransmissores/metabolismo , Receptores de Dopamina D1/metabolismo , Receptores de GABA-A/metabolismo , Ácido gama-Aminobutírico/metabolismoRESUMO
BACKGROUND: Bisphenol-A (BPA) is a polymerizing agent used in plastic bottles and several routinely used consumer items. It is classified among endocrine disrupting chemicals suspected to cause adverse health effects in mammals ranging from infertility and cancer to behavioral disorders. Work with the invertebrate lab model Caenorhabditis elegans has shown that BPA affects germ cells by disrupting double-stranded DNA break repair mechanisms. The current study utilizes this model organism to provide insight into low-dose and long-term behavioral effects of BPA and bisphenol-S (BPS), a supposed safer replacement for BPA. FINDINGS: Experiments presented in our report demonstrate that the effects of embryonic exposure to considerably low levels of BPA persist into adulthood, affecting neural functionality as assayed by measuring habituation to mechano-sensory stimuli in C. elegans. These results are noteworthy in that they are based on low-dose exposures, following the rationale that subtler effects that may not be morphologically apparent are likely to be discernible through behavioral changes. In addition, we report that embryonic exposure to BPS follows a pattern similar to BPA. CONCLUSIONS: Building upon previous observations using the C. elegans model, we have shown that exposure of embryos to BPA and BPS affects their behavior as adults. These long-term effects are in line with recommended alternate low-dose chemical safety testing approaches. Our observation that the effects of BPS are similar to BPA is not unexpected, considering their structural similarity. This, to our knowledge, is the first reported behavioral study on low-dose toxicity of any endocrine disrupting chemical in C. elegans.
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Compostos Benzidrílicos/toxicidade , Aprendizagem/efeitos dos fármacos , Fenóis/toxicidade , Efeitos Tardios da Exposição Pré-Natal , Sulfonas/toxicidade , Animais , Caenorhabditis elegans , Feminino , Masculino , GravidezRESUMO
Community health worker (CHW) interventions have potential to improve diabetes outcomes and reduce health disparities. However, few studies have explored patient perspectives of peer-delivered diabetes programs. The purpose of this qualitative study is to investigate possible benefits as well as risks of CHW-delivered peer support for diabetes from the perspectives of African American women living with type 2 diabetes in Jefferson County, Alabama. Four ninety-minute focus groups were conducted by a trained moderator with a written guide to facilitate discussion on the topic of CHWs and diabetes management. Participants were recruited from the diabetes education database at a safety-net hospital. Two independent reviewers performed content analysis to identify major themes using a combined deductive-inductive approach. There were 25 participants. Mean years with diabetes was 11.2 (range 6 months to 42 years). Participants were knowledgeable about methods for self-management but reported limited resources and stress as major barriers. Preferred CHW roles included liaison to the healthcare system and easily accessible information source. Participants preferred that the CHW be knowledgeable and have personal experience managing their own diabetes or assisting a family member with diabetes. Concerns regarding the CHW-model were possible breaches of confidentiality and privacy. The self-management strategies and barriers to management identified by participants were reflected in their preferred CHW roles and traits. These results suggest that African American women with diabetes in Alabama would support peer-led diabetes education that is community-based and socially and emotionally supportive.
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Negro ou Afro-Americano/psicologia , Agentes Comunitários de Saúde/organização & administração , Diabetes Mellitus Tipo 2/terapia , Conhecimentos, Atitudes e Prática em Saúde , Percepção , Adulto , Idoso , Alabama , Diabetes Mellitus Tipo 2/psicologia , Feminino , Grupos Focais , Humanos , Relações Interinstitucionais , Pessoa de Meia-Idade , Grupo Associado , Papel Profissional , Pesquisa Qualitativa , Provedores de Redes de Segurança/organização & administração , Autocuidado , Apoio Social , Fatores Socioeconômicos , Estresse Psicológico/psicologiaRESUMO
The 1983-1984 mortality event of the long-spined sea urchin Diadema antillarum reduced their population by up to 99% and was accompanied by a phase shift from coral dominated to algal dominated reefs in the Caribbean. Modest rebounds of D. antillarum populations in the Caribbean have been noted, and here we document the impacts of two major hurricanes (2017, Irma and Maria) and the 2022 disease outbreak on populations of D. antillarum found by targeted surveys in the urchin zone at nine fringing reef and three mangrove sites on St. John, USVI. D. antillarum populations at the reef sites had declined by 66% five months after the hurricanes but showed significant recovery just one year later. The impact of recent disease on these populations was much more profound, with all reef populations exhibiting a significant decline (96.4% overall). Fifteen months after the disease was first noted, D. antillarum at reef sites exhibited a modest yet significant recovery (15% pre-disease density). D. antillarum populations in mangrove sites were impacted by the hurricanes but exhibited much higher density than reef sites after the disease outbreak, suggesting that at D. antillarum in some locations may be less vulnerable to disease.
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Antozoários , Tempestades Ciclônicas , Animais , Água , Ilhas Virgens Americanas , Ecossistema , Densidade Demográfica , Ouriços-do-Mar , Região do Caribe , Recifes de CoraisRESUMO
The endocannabinoid system has been shown to be a powerful mediator of anxiety, learning and memory, as well as nociception behaviors. Exogenous cannabinoids like delta-9-tetrahydrocannabinol mimic the naturally occurring endogenous cannabinoids found in the mammalian central and peripheral nervous system. The hydrophobic properties of endocannabinoids mean that these psychoactive compounds require help with cellular transport. A family of lipid intracellular carriers called fatty acid-binding proteins (FABPs) can bind to endocannabinoids. Pharmacological inhibition or genetic deletion of FABP subtypes 5 and 7 elevates whole-brain anandamide (AEA) levels, a type of endocannabinoid. This study examined locomotor behavior, anxiety-like behavior, and social behavior in FABP5-/- and FABP7-/- mice. Furthermore, we measured N-methyl-D-aspartate (NMDA) receptor levels in the brain to help identify potential underlying mechanisms related to the behavioral findings. Results showed that both male and female FABP5-/- mice exhibited significantly lower activity when compared with both FABP5/7+/+ (control) and FABP7-/-. For social behavior, male, but not female, FABP5-/- mice spent more time interacting with novel mice compared with controls (FABP5/7+/+) and FABP7-/- mice. No significant difference was found for anxiety-like behavior. Results from the NMDA autoradiography revealed [3H] MK-801 binding to be significantly increased within sub-regions of the striatum in FABP7-/- compared with control. In summary, these results show that FABP5 deficiency plays a significant role in locomotion activity, exploratory behavior, as well as social interaction. Furthermore, FABP7 deficiency is shown to play an important role in NMDA receptor expression, while FABP5 does not.
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Ansiedade , Proteína 7 de Ligação a Ácidos Graxos , Proteínas de Ligação a Ácido Graxo , Locomoção , Camundongos Knockout , Receptores de N-Metil-D-Aspartato , Comportamento Social , Animais , Proteínas de Ligação a Ácido Graxo/metabolismo , Proteínas de Ligação a Ácido Graxo/genética , Ansiedade/metabolismo , Masculino , Feminino , Proteína 7 de Ligação a Ácidos Graxos/metabolismo , Locomoção/fisiologia , Camundongos , Receptores de N-Metil-D-Aspartato/metabolismo , Camundongos Endogâmicos C57BL , Transdução de Sinais , Encéfalo/metabolismo , N-Metilaspartato/metabolismo , Proteínas de NeoplasiasRESUMO
There has been an increasing use of cannabis during pregnancy in recent years. Studies have indicated that THC exposure in utero may increase the risk of attention deficits and memory impairments in adolescence. The goal of the present study is to investigate the effects of vaporized THC exposure during pregnancy on offspring memory and attention performance in early and late adolescence. Pregnant dams were exposed to vaporized THC (10 mg or 40 mg) daily from gestational day 2 until labor. Pups were given either a standard or a high-fat diet at weaning and tested in early and late adolescence in two memory tests, the Novel Object Recognition (NOR) test and the Morris Water Maze (MWM) test, and a test of attention, the Object-Based Attention (OBA) test. Rats exposed to low-dose THC showed significantly decreased object exploration in both the NOR and OBA tests, indicating decreased attention. Object exploration time in OBA was significantly lower in females than males. Additionally, post hoc analysis of MWM tests showed some differences in learning patterns for HD THC offspring in early adolescence, possibly due to diet interaction, but ultimate performance was not impacted. While there are existing studies examining prenatal exposure to THC in rodents, this is the first to our knowledge examining memory and attention in adolescence following vaporized THC exposure in utero, and we find indications that prenatal THC exposure may lead to attention deficits and altered memory performance.
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Atenção , Dronabinol , Efeitos Tardios da Exposição Pré-Natal , Animais , Feminino , Gravidez , Dronabinol/administração & dosagem , Masculino , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Atenção/efeitos dos fármacos , Ratos , Relação Dose-Resposta a Droga , Memória/efeitos dos fármacos , Fatores Sexuais , Reconhecimento Psicológico/efeitos dos fármacos , Ratos Sprague-Dawley , Dieta Hiperlipídica/efeitos adversos , Aprendizagem em Labirinto/efeitos dos fármacosRESUMO
AIMS: Preclinical studies have found that chronic ∆9-tetrahydrocannabinol (THC) treatment is directly associated with weight gain when introduced during adolescence and adulthood, but the effect of prenatal THC is unclear. Clinical studies have demonstrated prenatal exposure to THC is a prospective predictor of increased health risks associated with obesity. Our study aims to examine prenatal THC impact on obesity risks in males and females throughout adolescence using a clinically relevant inhalation model. METHODS: Pregnant rats were exposed to one of the following from gestational day 2 through birth: 10 mg THC, 40 mg THC, or air. Daily 10-min inhalations were conducted in each animal from 0900 to 1200. Offspring from each treatment group were given either a high-fat diet (HFD) or a normal diet (ND). Food and bodyweights were collected daily, while circadian activity, locomotion, and exercise were measured periodically (PND 21-60). Pregnancy weight gain and birth weight were collected to determine early-life developmental effects. RESULTS: Rats prenatally treated with low-dose THC (LDTHC) generally had lower dark-cycle activity compared with control counterparts, but this altered activity was not observed at the higher dose of THC (HDTHC). In terms of open-field activity, THC doses displayed a general increase in locomotion. In addition, the LDTHC male rats in the ND showed significantly greater exploratory behavior. Prenatal THC had dose-dependent effects on maternal weight gain and birth weight. CONCLUSIONS: Overall, our findings indicate there are some activity-related and developmental effects of prenatal THC, which may be related to obesity risks later in life.
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Dronabinol , Efeitos Tardios da Exposição Pré-Natal , Gravidez , Feminino , Ratos , Masculino , Animais , Humanos , Peso ao Nascer , Dronabinol/farmacologia , Dieta , Obesidade/etiologia , LocomoçãoRESUMO
Rationale Clinical research has shown that prenatal exposure to nicotine may result in increased obesity risk later in life. Preclinical research has corroborated this finding, but few studies have investigated inhaled nicotine or the interaction with diet on obesity risk. Objective The aim of this study was to investigate the effects of prenatal nicotine exposure on both direct and indirect obesity measures, with both sex and diet as factors. Methods Pregnant rats were exposed to either vehicle or nicotine vapor (24 mg/mL or 59 mg/mL) throughout the entire gestational period. Offspring from each treatment group were given either a normal diet or a high fat diet starting at postnatal day 22. Caloric intake, body weight, spontaneous locomotion, sleep/wake activity, and voluntary exercise were measured throughout adolescence. Pregnancy weight gain and pup birthweights were collected to further measure developmental effects of prenatal nicotine exposure. Results Both maternal weight gain during pregnancy and pup weight at birth were decreased with prenatal nicotine exposure. Early adolescent males showed increased spontaneous activity in the open field following prenatal nicotine exposure compared to vehicle counterparts, particularly those given high-fat diet. Additionally, high dose nicotine prenatal treated males ran significantly less distance on the running wheel in late adolescence compared to vehicle counterparts, in the normal diet group only. Conclusion The results presented here show decreased birthweight, hyperactivity, and decreased voluntary exercise in adolescence following prenatal nicotine exposure in dose, sex, and diet dependent manners, which could lead to increased obesity risk in adulthood.
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Peso ao Nascer , Dieta Hiperlipídica , Locomoção , Nicotina , Efeitos Tardios da Exposição Pré-Natal , Animais , Feminino , Nicotina/administração & dosagem , Nicotina/farmacologia , Gravidez , Masculino , Ratos , Dieta Hiperlipídica/efeitos adversos , Peso ao Nascer/efeitos dos fármacos , Locomoção/efeitos dos fármacos , Condicionamento Físico Animal/fisiologia , Fatores Sexuais , Ratos Sprague-Dawley , Obesidade , Relação Dose-Resposta a Droga , Peso Corporal/efeitos dos fármacosRESUMO
Epidermal/brain fatty acid-binding protein 5 (FABP5) plays an integral role in the intracellular trafficking of bioactive lipids/endocannabinoids and the subsequent initiation of cellular cascades affecting cannabinoid and dopamine (DA) systems. Social isolation (SI) and environmental enrichment (EE) during adolescence have been shown to impact DA signaling, and, specifically, DA transporter (DAT) and receptor levels of DA type 1 (D1) and 2 (D2); however, the relationship between FABP5, environment and DA signaling remains unclear. The present study quantified DAT and DA receptor levels in male/female FABP5-/- and FABP5+/+ mice raised in either SI or EE. Results showed that FABP5-/- mice had 6.09-8.81% greater D1 levels in striatal sub-regions of the caudal brain, independent of sex or environment. D1 levels were 8.03% greater only in the olfactory tubercle of enrichment-reared animals. In summary, these results supported that FABP5 plays an important function in regulating striatal DA signaling, and this may have important implications as a target with therapeutic potential for various psychiatric disorders.
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Emerging evidence indicates that the endogenous cannabinoid system modulates the behavioral and physiological effects of nicotine. Fatty acid-binding proteins (FABPs) are among the primary intracellular trafficking mechanisms of endogenous cannabinoids, such as anandamide. To this end, changes in FABP expression may similarly impact the behavioral manifestations associated with nicotine, particularly its addictive properties. FABP5 +/+ and FABP5 -/- mice were tested for nicotine-conditioned place preference (CPP) at two different doses (0.1 or 0.5 mg/kg). The nicotine-paired chamber was assigned as their least preferred chamber during preconditioning. Following 8 days of conditioning, the mice were injected with either nicotine or saline. The mice were allowed to access to all the chambers on the test day, and their times spent in the drug chamber on the preconditioning versus the test days were used to examine the drug preference score. The CPP results showed that the FABP5 -/- mice displayed a higher place preference for 0.1 mg/kg nicotine than the FABP5 +/+ mice, while no CPP difference was observed for 0.5 mg/kg nicotine between the genotypes. In conclusion, FABP5 plays an important role in regulating nicotine place preference. Further research is warranted to identify the precise mechanisms. The results suggest that dysregulated cannabinoid signaling may impact nicotine-seeking behavior.
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Background: Previous research has outlined the health benefits of exercise including its therapeutic potential for substance use disorders (SUD). These data have already been utilized and it is now common to find exercise as part of SUD treatment and relapse prevention programs. However, we need to better understand different exercise regimens and determine which would be the most beneficial for SUDs. Recently, high intensity interval training (HIIT) has gained attention in comparison with aerobic and resistance exercise. Little is known regarding the neurobiological mechanisms of HIIT, including its effects on dopamine signaling and receptor levels in the brain. The present study examined the effects of chronic HIIT exercise on dopamine signaling as measured by dopamine type 1-like receptor (D1R)-like, dopamine type 2-like receptor (D2R)-like, and tyrosine hydroxylase (TH) quantification in the brains of male and female rats as measured by [3H] SCH 23390 and [3H] spiperone autoradiography, and TH-immunoreactive optical density values. Methods: Rats were separated in two groups: sedentary and HIIT exercise. Exercise was on a treadmill for 30 min daily (10 3 min cycles) for six weeks with progressive speed increased up to 0.8 mph (21.5 m/min). Results: Results showed for D2R-like binding, a significant effect across the ventral caudate putamen (V CPU) between sexes, such that mean D2R-like binding was 14% greater for males than females. In the nucleus accumbens shell (Nac Shell), the HIIT Exercise rats showed 16% greater D2R-like binding as compared to the sedentary rats. No significant effects of HIIT exercise were found across groups for brain D1R-like binding levels or TH expression. Conclusion: These results suggest that HIIT exercise can modulate dopamine signaling by way of increased D2R. These findings support the premise that HIIT exercise plays an important role in dopamine signaling and, may provide a potential mechanism for how HIIT exercise can impact the brain and behavior.
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Dopamina , Treinamento Intervalado de Alta Intensidade , Feminino , Masculino , Animais , Ratos , Encéfalo , Transdução de Sinais , EspiperonaRESUMO
Fatty acid binding protein 5 (FABP5) interacts with the endocannabinoid system in the brain via intracellular transport of anandamide, as well as Δ9-tetrahydrocannabinol (THC), the main psychoactive component of cannabis. Previous work has established the behavioral effects of genetic deletion of FABP5, but not in the presence of THC. The present study sought to further elucidate the role of FABP5 on the pharmacokinetic and behavioral response to THC through global deletion. Adult FABP5+/+ and FABP5-/- mice were tested for behavioral response to THC using Open Field (OF), Novel Object Recognition (NOR), T-Maze, Morris Water Maze (MWM), and Elevated Plus Maze (EPM). An additional cohort of mice was used to harvest blood, brains, and liver samples to measure THC and metabolites after acute administration of THC. Behavioral tests showed that some cognitive deficits from FABP5 deletion, particularly in MWM, were blocked by THC administration, while this was not observed in other measures of memory and anxiety (such as T-Maze and EPM). Measurement of THC and metabolites in blood serum and brain tissue through UPLC-MS/MS analysis showed that the pharmacokinetics of THC was altered by FABP5. The present study shows further evidence of the importance of FABP5 in cognitive function. Additionally, results showed that FABP5 is an important regulator of the physiological effects and pharmacokinetics of THC.
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Dronabinol , Proteínas de Ligação a Ácido Graxo , Espectrometria de Massas em Tandem , Animais , Camundongos , Encéfalo/metabolismo , Cromatografia Líquida , Cognição , Dronabinol/farmacologia , Proteínas de Ligação a Ácido Graxo/genética , Proteínas de Ligação a Ácido Graxo/metabolismo , Proteínas de Ligação a Ácido Graxo/farmacologiaRESUMO
Haloperidol and olanzapine are first and second-generation antipsychotic (neuroleptic) medications approved to treat schizophrenia. Glutamate signaling is known to play an important role in the manifestation of schizophrenia symptoms, as phencyclidine, a non-competitive N-methyl-D-aspartate receptor (NMDAR) antagonist, replicates and exasperates these symptoms. While initial reports show that neuroleptic treatments can impact aspects of NMDAR expression, there is little attention on the interaction between neuroleptics and dietary conditions. Thus, we examined the impact of chronic haloperidol and olanzapine treatment under both normal and high-fat dietary conditions on NMDAR expression. Adult male rats were treated for 28-days with either oral vehicle, haloperidol (1.5 mg/kg), or olanzapine (10 mg/kg), and fed either a standard control diet or a high-fat diet. In-vitro receptor autoradiography binding was performed using [3H] MK-801 as a measure of NMDAR expression. Results showed that olanzapine, irrespective of the diet, significantly decreased [3H] MK-801 binding within the cingulate cortex, substantia nigra, insular cortex, piriform cortex, ectorhinal cortex and perirhinal cortex, the forelimb region of the somatosensory cortex, and all quadrants of the caudate-putamen. In contrast, haloperidol treatment did not impact [3H] MK-801 binding, and we also report no effect of diet on [3H] MK-801 binding. These data suggest that the effects seen in olanzapine treatment are not mediated by diet, nor does a 28-day chronic high-fat diet alter [3H] MK-801 binding. Furthermore, these data also importantly support that combined consumption of a high-fat diet and pharmacological treatments are not immediately detrimental to NMDARs and contribute to the expansive literature of precision medicine.
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Antipsicóticos , Haloperidol , Animais , Antipsicóticos/uso terapêutico , Benzodiazepinas/farmacologia , Dieta , Maleato de Dizocilpina/farmacologia , Haloperidol/farmacologia , Masculino , Olanzapina , Ratos , Ratos Sprague-Dawley , Receptores de N-Metil-D-Aspartato , Substância NegraRESUMO
Fatty acid-binding proteins (FABPs) are intracellular carriers of bioactive lipids and play a role in the trafficking of endocannabinoids as well as polyunsaturated fatty acids. Mice lacking the FABP5 gene have memory impairments. Environmental enrichment is a potent manipulation known to rescue or improve memory performance. The extent to which the memory impairments in FABP5 knockout (KO) mice can be rescued or improved through environmental conditions remains to be understood. To address this, we raised wild type (WT) and FABP5 KO mice in either socially isolated or environmental enrichment conditions during adolescence. Once in adulthood, mice were tested for Novel Object Recognition (NOR), T-maze, and Morris Water Maze (MWM) to evaluate memory performance. Mice were then euthanized to assess hippocampal brain-derived neurotrophic factor (BDNF) concentrations. MWM results showed that male FABP5 KO mice performed worse compared to WT counterparts. Male and female mice raised in an enriched environment improved performance regardless of genotype. Results on the NOR test showed that male FABP5 KO mice displayed lower object recognition compared to WT counterparts across both environments. No differences of genotype or environment were seen in female mice. T-maze findings revealed impaired performance in socially isolated FABP5 KO mice. Adolescent environmental enrichment rescued this deficit in male, but not female, FABP5 KO mice. Lastly, environmental enrichment increased hippocampal BDNF levels in male WT mice only. Our results corroborate the previously observed role of the FABP5 gene on memory performance and identify an important interaction with the environment during adolescence.
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Fator Neurotrófico Derivado do Encéfalo , Proteínas de Ligação a Ácido Graxo , Transtornos da Memória , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Proteínas de Ligação a Ácido Graxo/genética , Proteínas de Ligação a Ácido Graxo/metabolismo , Feminino , Hipocampo/metabolismo , Masculino , Transtornos da Memória/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismoRESUMO
Fatty acid-binding proteins (FABPs) are intracellular chaperone proteins involved in the trafficking of n-3 polyunsaturated fatty acids and endocannabinoids. Inhibiting two of the main FABP subtypes found in the brain (FABP5 and FABP7) hinders endocannabinoid uptake and hydrolysis. Prior data indicates that cannabinoid receptor stimulation can ameliorate the consequences associated with chronic stress. To this end, FABP expression may play a similar role in response to stressful conditions. Male C57BL/6 J (WT) and FABP7 knockout (KO) mice were assigned to either a non-stress cohort or an unpredictable chronic mild stress (UCMS) cohort for a period of 4 weeks. Immediately after 4 weeks, mice were injected with [18F]2-fluoro-2-deoxy-d-glucose (FDG) and scanned using micro positron emission tomography (mPET) to examine brain glucose metabolism (BGluM). WT mice exposed to UCMS showed reduced BGluM in striatal, cortical, and hypothalamic regions and showed increased BGluM in the hippocampus, thalamus, periaqueductal gray, superior colliculi, inferior colliculi, and cerebellum. In contrast, there were limited effects of UCMS on BGluM in FABP7 KO mice, with a reduction in the thalamus, periaqueductal gray, and superior colliculi. These findings provide novel insight into FABP7 expression and indicate this gene to play an important role in response to aversive stimuli.
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Proteínas de Ligação a Ácido Graxo , Glucose , Animais , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Endocanabinoides/metabolismo , Proteína 7 de Ligação a Ácidos Graxos/metabolismo , Proteínas de Ligação a Ácido Graxo/genética , Proteínas de Ligação a Ácido Graxo/metabolismo , Glucose/metabolismo , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos KnockoutRESUMO
Clinical and preclinical studies have shown dysfunctions in genetic expression and neurotransmission of γ-Aminobutyric acid (GABA), GABAA receptor subunits, and GABA-synthesizing enzymes GAD67 and GAD65 in schizophrenia. It is well documented that there is significant weight gain after chronic neuroleptic treatment in humans. While there are limited studies on the effects of diet on GABA signaling directly, a change in diet has been used clinically as an adjunct to treatment for schizophrenic relief. In this study, rats chronically consumed either a chow diet (CD) or a 60% high-fat diet (HFD) and drank from bottles that contained one of the following solutions: water, haloperidol (1.5 mg/kg), or olanzapine (10 mg/kg) for four weeks. Rats were then euthanized and their brains were processed for GABAA in-vitro receptor autoradiography using [3H] flunitrazepam. A chronic HFD treatment yielded significantly increased [3H] flunitrazepam binding in the rat cerebellum independent of neuroleptic treatment. The desynchronization between the prefrontal cortex and the cerebellum is associated with major cognitive and motor dysfunctions commonly found in schizophrenic symptomatology, such as slowed reaction time, motor dyscoordination, and prefrontal activations related to speech fluency and cognitive alertness. These data support the notion that there is a dietary effect on GABA signaling within the cerebellum, as well as the importance of considering nutritional intervention methods as an adjunct treatment for patients chronically treated with neuroleptics. Finally, we indicate that future studies involving the analysis of individual patient's genetic profiles will further assist towards a precision medicine approach to the treatment of schizophrenia.
Assuntos
Antipsicóticos/administração & dosagem , Cerebelo/efeitos dos fármacos , Dieta Hiperlipídica , Flunitrazepam/metabolismo , Haloperidol/administração & dosagem , Esquizofrenia/tratamento farmacológico , Animais , Antipsicóticos/farmacologia , Autorradiografia , Encéfalo/metabolismo , Haloperidol/farmacologia , Masculino , Olanzapina/administração & dosagem , Olanzapina/farmacologia , Córtex Pré-Frontal/metabolismo , Ensaio Radioligante , Ratos , Ácido gama-Aminobutírico/metabolismoRESUMO
Asthma, a chronic childhood disease, has resulted in increased emergency department (ED) visits with high costs. Many asthma ED visits are nonemergent and could be treated in outpatient clinics. Literature has concluded that a 2-day course of oral dexamethasone has comparable outcomes to a 5-day course of prednisone in the ED and hospital setting. A retrospective chart review was performed on children requiring in-house treatment with a corticosteroid (dexamethasone n = 23, prednisone n = 40) for acute asthma exacerbations at an ambulatory medical home. The rates of hospital admissions, ED visits, and symptom follow-up were similar between the 2 groups ( P > .05). The cost for a course of dexamethasone was US$1.28 versus US$16.20 for prednisolone. The average cost for an asthma exacerbation office visit was US$79.89 compared with US$3113.28 for an ED visit. A 2-day course of oral dexamethasone appears to be a promising clinical and cost-effective treatment for acute asthma exacerbations at the primary care level.
Assuntos
Instituições de Assistência Ambulatorial , Asma/tratamento farmacológico , Dexametasona/uso terapêutico , Glucocorticoides/uso terapêutico , Sons Respiratórios/efeitos dos fármacos , Doença Aguda , Administração Oral , Asma/economia , Asma/fisiopatologia , Criança , Dexametasona/administração & dosagem , Dexametasona/economia , Feminino , Seguimentos , Glucocorticoides/administração & dosagem , Glucocorticoides/economia , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Prednisolona/economia , Prednisolona/uso terapêutico , Recidiva , Sons Respiratórios/fisiopatologia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive disorder resulting in irreversible scarring of the lung parenchyma. Although fatigue is a prominent symptom for patients with IPF, little is known about sleep quality in patients with IPF. METHODS: In this cross-sectional study of 41 patients with IPF from a prospectively designed cohort, we ascertained sleep quality by means of the Pittsburgh sleep quality index (PSQI) and the Epworth sleepiness scale. Health status, baseline demographics, and physiologic parameters were also assessed. RESULTS: Patients with IPF reported extremely poor sleep quality and high frequency of daytime sleepiness, which differs significantly from normal control populations. Further, poor sleep quality was not associated with body mass index, age, gender, or lung function. This population also demonstrated extremely poor health status in a number of domains, including physical function and vitality. Poor sleep quality (by the global PSQI) was significantly associated with decreased quality of life (QOL) in several domains, including role of physical function (r = - 0.58, p = 0.001), vitality (r = - 0.43, p = 0.015), and role of emotions (r = - 0.40, p = 0.023). CONCLUSIONS: Poor sleep quality is extremely common in patients with IPF and is not predicted by variables traditionally associated with sleep-disordered breathing. Further, poor sleep quality is associated with poor QOL. These findings suggest that systematic evaluation of the cause of poor sleep quality in IPF is merited.