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Cancer is a severe health condition and considered one of the major healthcare issues and is in need of innovative strategy for a cure. The current study aimed to investigate the chemical profile of Trigonella hamosa L. and a potential molecular approach to explain its regulation in cancer progression through an inflammatory mediator (COX-2) in A549 non-small lung cancer cell lines via in silico, mechanistic and molecular aspects. T. hamosa was extracted and then subjected to a CCK-8 cell viability assay in different cancer cell lines including MDA-MB-231, A549 and HCT-116. Total extract was subjected to several chromatographic techniques to yield orientin (OT); the structure was elucidated by inspection of NMR spectroscopic data. To achieve anticancer effects of OT, a cell viability assay using a CCK-8 kit, immunoprecipitation by Western blot, cell migration using a wound healing assay, cell invasion using a Matrigel-Transwell assay, apoptosis by AO/EB dual staining, flow cytometric analysis and DAPI staining, a silenced COX-2 model to determine PGE-2 production and real-time PCR and Western blot of BCL-2, CYP-1A1, iNOS and COX-2 markers were carried out. The results demonstrated that OT decreased the cell proliferation and controlled cell migration and invasive properties. OT destabilized the COX-2 mRNA and downregulated its expression in A549 cell lines. Virtual binding showed interaction (binding energy -10.43) between OT and COX-2 protein compared to the selective COX-2 inhibitor celecoxib (CLX) (binding energy -9.4). The OT-CLX combination showed a superior anticancer effect. The synergistic effect of OT-CLX combination was noticed in controlling the migration and invasion of A549 cell lines. OT-CLX downregulated the expression of BCL-2, iNOS and COX-2 and activated the proapoptotic gene CYP-1A1. OT mitigated the COX-2 expression via upregulation of miR-26b and miR-146a. Interestingly, COX-2-silenced transfected A549 cells exhibited reduced expression of miR-26b and miR-146a. The findings confirmed the direct interaction of OT with COX-2 protein. PGE-2 expression was quantified in both naïve and COX-2-silenced A549 cells. OT downregulated the release of PGE-2 in both tested conditions. These results confirmed the regulatory effect of OT on A549 cell growth in a COX-2-dependent manner. OT activated apoptosis via activation of CYP-1A1 expression in an independent manner. These results revealed that the OT-CLX combination could serve as a potential synergistic treatment for effective inflammatory-mediated anticancer strategies.
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The original version of this article unfortunately does not include the second affiliating institution of Dr. Munder A. Zagaar. "Department of Pharmacy Pracce and Clinical Health Sciences, Texas Southern University, Houston, TX 77004" should have been included on the paper.
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Context: Date palms, along with their fruits' dietary consumption, possess enormous medicinal and pharmacological activities manifested in their usage in a variety of ailments in the various traditional systems of medicine. In recent years, the identification of progenitor cells in the adult organ systems has opened an altogether new approach to therapeutics, due to the ability of these cells to repair the damaged cells/tissues. Hence, the concept of developing therapeutics, which can mobilize endogenous progenitor cells, following tissue injury, to enhance tissue repair process is clinically relevant. Objectives: The present study investigates the potential of date of palm fruit extracts in repairing tissue injury following myocardial infarction (MI) potentially by mobilizing circulating progenitor cells. Methods: Extracts of four different varieties of date palm fruits common in Saudi Arabia eastern provision were scrutinized for their total flavonoid, total phenolic, in vitro antioxidant capacity, as well as their effects on two different rodent MI models. Results: High concentrations of phenolic and flavonoid compounds were observed in date palm fruit extracts, which contributed to the promising antioxidant activities of these extracts and the observed high protective effect against various induced in vivo MI. The extracts showed ability to build up reserves and to mobilize circulating progenitor cells from bone marrow and peripheral circulation to the site of myocardial infraction. Conclusion: Date palm fruit extracts have the potential to mobilize endogenous circulating progenitor cells, which can promote tissue repair following ischemic injury.
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We have investigated the neuroprotective effect of chronic caffeine treatment on basal levels of memory-related signaling molecules in area CA1 of sleep-deprived rats. Animals in the caffeine groups were treated with caffeine in drinking water (0.3g/l) for four weeks before they were REM sleep-deprived for 24h in the Modified Multiple Platforms paradigm. Western blot analysis of basal protein levels of plasticity- and memory-related signaling molecules in hippocampal area CA1 showed significant down regulation of the basal levels of phosphorylated- and total-CaMKII, phosphorylated- and total-CREB as well as those of BDNF and CaMKIV in sleep deprived rats. All these changes were completely prevented in rats that chronically consumed caffeine. The present findings suggest an important neuroprotective property of caffeine in sleep deprivation.
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Región CA1 Hipocampal/efectos de los fármacos , Cafeína/farmacología , Estimulantes del Sistema Nervioso Central/farmacología , Fármacos Neuroprotectores/farmacología , Transducción de Señal , Privación de Sueño/metabolismo , Sueño REM/efectos de los fármacos , Animales , Factor Neurotrófico Derivado del Encéfalo/genética , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Región CA1 Hipocampal/metabolismo , Región CA1 Hipocampal/fisiología , Cafeína/uso terapéutico , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/genética , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/metabolismo , Estimulantes del Sistema Nervioso Central/uso terapéutico , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/genética , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Regulación hacia Abajo , Masculino , Fármacos Neuroprotectores/uso terapéutico , Ratas , Ratas Wistar , Privación de Sueño/tratamiento farmacológicoRESUMEN
The dentate gyrus (DG) and CA1 regions of the hippocampus are intimately related physically and functionally, yet they react differently to insults. The purpose of this study was to determine the protective effects of regular treadmill exercise on late phase long-term potentiation (L-LTP) and its signaling cascade in the DG region of the hippocampus of rapid eye movement (REM) sleep-deprived rats. Adult Wistar rats ran on treadmills for 4 weeks then were acutely sleep deprived for 24 h using the modified multiple platform method. After sleep deprivation, the rats were anesthetized and L-LTP was induced in the DG region. Extracellular field potentials from the DG were recorded in vivo, and levels of L-LTP-related signaling proteins were assessed both before and after L-LTP expression using immunoblot analysis. Sleep deprivation reduced the basal levels of phosphorylated cAMP response element-binding protein (P-CREB) as well as other upstream modulators including calcium/calmodulin kinase IV (CaMKIV) and brain-derived neurotrophic factor (BDNF) in the DG of the hippocampus. Regular exercise prevented impairment of the basal levels of P-CREB and total CREB as well as those of CaMKIV in sleep-deprived animals. Furthermore, regular exercise prevented sleep deprivation-induced inhibition of L-LTP and post-L-LTP downregulation of P-CREB and BDNF levels in the DG. The current findings show that our exercise regimen prevents sleep deprivation-induced deficits in L-LTP as well as the basal and poststimulation levels of key signaling molecules.
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Giro Dentado/metabolismo , Giro Dentado/fisiopatología , Potenciación a Largo Plazo , Condicionamiento Físico Animal , Transducción de Señal , Privación de Sueño/prevención & control , Privación de Sueño/fisiopatología , Animales , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Proteína Quinasa Tipo 4 Dependiente de Calcio Calmodulina/metabolismo , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Masculino , Fosforilación , Ratas WistarRESUMEN
The CA1 and dentate gyrus (DG) are physically and functionally closely related areas of the hippocampus, but they differ in various respects, including their reactions to different insults. The purpose of this study was to determine the protective effects of chronic caffeine treatment on late-phase long-term potentiation (L-LTP) and its signalling cascade in the DG area of the hippocampus of rapid eye movement sleep-deprived rats. Rats were chronically treated with caffeine (300 mg/L drinking water) for 4 weeks, after which they were sleep-deprived for 24 h. L-LTP was induced in in anaesthetized rats, and extracellular field potentials from the DG area were recorded in vivo. The levels of L-LTP-related signalling proteins were assessed by western blot analysis. Sleep deprivation markedly reduced L-LTP magnitude, and basal levels of total cAMP response element-binding protein (CREB), phosphorylated CREB (P-CREB), and calcium/calmodulin kinase IV (CaMKIV). Chronic caffeine treatment prevented the reductions in the basal levels of P-CREB, total CREB and CaMKIV in sleep-deprived rats. Furthermore, caffeine prevented post-L-LTP sleep deprivation-induced downregulation of P-CREB and brain-derived neurotrophic factor in the DG. The current findings show that caffeine treatment prevents acute sleep deprivation-induced deficits in brain function.
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Cafeína/administración & dosificación , Giro Dentado/efectos de los fármacos , Giro Dentado/fisiopatología , Potenciación a Largo Plazo/efectos de los fármacos , Privación de Sueño/fisiopatología , Sueño REM , Animales , Ondas Encefálicas/efectos de los fármacos , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Proteína Quinasa Tipo 4 Dependiente de Calcio Calmodulina/metabolismo , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Giro Dentado/metabolismo , Potenciales Postsinápticos Excitadores/efectos de los fármacos , Masculino , Fosforilación , Ratas , Ratas Wistar , Transducción de Señal/efectos de los fármacos , Privación de Sueño/metabolismoRESUMEN
To investigate mechanisms by which thymoquinone (TQ) can prevent methotrexate- (MTX-) induced hepatorenal toxicity, TQ (10 mg/kg) was administered orally for 10 days. In independent rat groups, MTX hepatorenal toxicity was induced via 20 mg/kg i.p. at the end of day 3 of experiment, with or without TQ. MTX caused deterioration in kidney and liver function, namely, blood urea nitrogen, creatinine, alanine aminotransferase, and aspartate aminotransferase. MTX also caused distortion in renal and hepatic histology, with significant oxidative stress, manifested by decrease in reduced glutathione and catalase, as well as increase in malondialdehyde levels. In addition, MTX caused nitrosative stress manifested by increased nitric oxide, with upregulation of inducible nitric oxide synthase. Furthermore, MTX caused hepatorenal inflammatory effects as shown by increased tumor necrosis factor-α, besides upregulation of necrosis factor-κB and cyclooxygenase-2 expressions. MTX also caused apoptotic effect, as it upregulated caspase 3 in liver and kidney. Using TQ concurrently with MTX restored kidney and liver functions, as well as their normal histology. TQ also reversed oxidative and nitrosative stress, as well as inflammatory and apoptotic signs caused by MTX alone. Thus, TQ may be beneficial adjuvant that confers hepatorenal protection to MTX toxicity via antioxidant, antinitrosative, anti-inflammatory, and antiapoptotic mechanisms.
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Benzoquinonas/farmacología , Riñón/efectos de los fármacos , Riñón/metabolismo , Hígado/efectos de los fármacos , Hígado/metabolismo , Malondialdehído/toxicidad , Metotrexato/toxicidad , Animales , Antioxidantes/metabolismo , Apoptosis/efectos de los fármacos , Ciclooxigenasa 2/metabolismo , Glutatión/metabolismo , Masculino , FN-kappa B/metabolismo , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas WistarRESUMEN
The assessment of skin uptake and clearance are important to determine the efficiency and systemic safety of dermatological formulations. The objective of this study was to assess the skin uptake, clearance and possible systemic delivery of ciclopirox following topical application in Wistar rats. In vitro studies (3 h) were carried out in excised pig skin to assess the permeation and retention capacity of ciclopirox in skin layers using gel formulations (1% and 2% w/v). In vivo dermatopharmacokinetics (DPK) parameters were determined by measuring the drug levels in the skin as a function of time post application (0.5, 1, 1.5 and 2 h) and post removal (3, 4, 6 and 8 h) of the formulation in Wistar rats. The plasma drug concentrations were also determined in the same animals. In vitro data indicate the low permeability and high retention of ciclopirox in the stratum corneum. The DPK data observed indicate a higher Cmax value (175.43 ± 25.62 µg/cm2) and AUC (632.14 ± 102.26 µg.h/cm2) with the 2% (w/v) gel formulation. Further, the skin elimination of ciclopirox follows first order kinetics with a short half-life (t1/2 ~2 h). The fraction of drug reaching the systemic circulation was found to be significantly low (~0.15% of the applied dose). A relation between the drug concentration in the skin layers and the plasma was observed with a short lag period. The topical availability of ciclopirox was found to be relatively low and endured rapid clearance with minimal systemic uptake.
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Antifúngicos/farmacocinética , Piridonas/farmacocinética , Piel/metabolismo , Administración Cutánea , Animales , Ciclopirox , Técnicas In Vitro , Ratas , Ratas Wistar , Absorción Cutánea , PorcinosRESUMEN
Extensive research on transmucosal drug delivery in the past few decades has resulted in the clinical application of several drug molecules through the buccal route. Interestingly, most of the new chemical moieties under clinical trials are being screened for their potential to deliver through the buccal cavity. In this context, buccal film offers several advantages including convenient dosing and better patient compliance. However, the greatest challenge is to develop a high quality buccal film which also necessitates constant evaluation and understanding the performance of the dosage form, the critical steps to achieve a successful product development. Despite the intense focus on buccal film based drug delivery system, there are no official standardized methods for its evaluation. Significant efforts have been made to demonstrate and improve the efficacy, potency and safety of buccal film using in vitro, ex vivo and in vivo assessments. Besides the physical properties of the film, several other parameters such as residence time, mucoadhesion, drug release, in vitro and in vivo buccal permeation profiles and absorption kinetics of the drug are examined while characterizing the prepared buccal films. However, various research groups have employed different methods and experimental conditions to evaluate the formulation, which has limited the comparison of data between the research groups. This review provides an overview about the various parameters that are considered and assessed as a part of formulation development to ensure quality product with desired characteristics.
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Portadores de Fármacos/química , Ensayo de Materiales/métodos , Modelos Biológicos , Mucosa Bucal/metabolismo , Polímeros/química , Administración Bucal , Animales , Cristalización , Elasticidad , Diseño de Equipo , Ensayo de Materiales/instrumentación , Preparaciones Farmacéuticas/administración & dosificación , Preparaciones Farmacéuticas/química , Porosidad , Solubilidad , Propiedades de Superficie , Resistencia a la Tracción , Adhesivos TisularesRESUMEN
BACKGROUND: The new combination of moxifloxacin HCl and cefixime trihydrate is approved for the treatment of lower respiratory tract infections in adults. At initial formulation development and screening stage a fast and reliable method for the dissolution and release testing of moxifloxacin and cefixime were highly desirable. The zero order overlaid UV spectra of moxifloxacin and cefixime showed >90% overlapping. Hence, simple, accurate precise and validated two derivative spectrophotometric methods have been developed for the determination of moxifloxacin and cefixime. METHODS: In the first derivative spectrophotometric method varying concentration of moxifloxacin and cefixime were prepared and scanned in the range of 200 to 400 nm and first derivative spectra were calculated (n = 1). The zero crossing wavelengths 287 nm and 317.9 nm were selected for determination of moxifloxacin and cefixime, respectively. In the second method the first derivative of ratio spectra was calculated and used for the determination of moxifloxacin and cefixime by measuring the peak intensity at 359.3 nm and 269.6 nm respectively. RESULTS: Calibration graphs were established in the range of 1-16 µg /mL and 1-15 µg /mL for both the drugs by first and ratio first derivative spectroscopic methods respectively with good correlation coefficients. Average accuracy of assay of moxifloxacin and cefixime were found to be 100.68% and 98 93%, respectively. Relative standard deviations of both inter and intraday assays were less than 1.8%. Moreover, recovery of moxifloxacin and cefixime was more than 98.7% and 99.1%, respectively. CONCLUSIONS: The described derivative spectrophotometric methods are simple, rapid, accurate, precise and excellent alternative to sophisticated chromatographic techniques. Hence, the proposed methods can be used for the quality control of the cited drugs and can be extended for routine analysis of the drugs in formulations.
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Cardiovascular disease (CVD) is the leading cause of death worldwide. According to the World Health Organization (WHO), an estimate of 17.3 million people died from CVDs in 2008 and by 2030, the number of deaths is estimated to reach almost 23.6 million. Despite the development of a variety of treatment options, heart failure management has failed to inhibit myocardial scar formation and replace the lost cardiomyocyte mass with new functional contractile cells. This shortage is complicated by the limited ability of the heart for self-regeneration. Accordingly, novel management approaches have been introduced into the field of cardiovascular research, leading to the evolution of gene- and cell-based therapies. Stem cell-based therapy (aka, cardiomyoplasty) is a rapidly growing alternative for regenerating the damaged myocardium and attenuating ischemic heart disease. However, the optimal cell type to achieve this goal has not been established yet, even after a decade of cardiovascular stem cell research. Mesenchymal stem cells (MSCs) in particular have been extensively investigated as a potential therapeutic approach for cardiac regeneration, due to their distinctive characteristics. In this paper, we focus on the therapeutic applications of MSCs and their transition from the experimental benchside to the clinical bedside.
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In addition to genetic aspects, environmental factors such as stress may also play a critical role in the etiology of the late onset, sporadic Alzheimer's disease (AD). The present study examined the effect of chronic psychosocial stress in a sub-threshold Aß (subAß) rat model of AD on long-term depression by two techniques: electrophysiological recordings of synaptic plasticity in anesthetized rats, and immunoblot analysis of memory- and AD-related signaling molecules. Chronic psychosocial stress was induced using a rat intruder model. The subAß rat model of AD, which was intended to represent outwardly normal individuals with a pre-disposition to AD, was induced by continuous infusion of 160 pmol/day Aß1â42 via a 14-day i.c.v. osmotic pump. Results from electrophysiological recordings showed that long-term depression evoked in stress/subAß animals was significantly enhanced compared with that in animals exposed to stress or subAß infusion alone. Molecular analysis of various signaling molecules 1 h after induction of long-term depression revealed an increase in the levels of calcineurin and phosphorylated CaMKII in groups exposed to stress compared with other groups. The levels of the brain-derived neurotrophic factor (BDNF) were significantly decreased in stress/subAß animals but not in stress or subAß animals. In addition, the levels of beta-site amyloid precursor protein cleaving enzyme were markedly increased in stress/subAß. These findings suggest that chronic stress may accelerate the impairment of synaptic plasticity and consequently cognition in individuals 'at-risk' for AD.
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Enfermedad de Alzheimer/psicología , Péptidos beta-Amiloides/farmacología , Depresión/psicología , Fragmentos de Péptidos/farmacología , Medio Social , Estrés Psicológico/psicología , Enfermedad de Alzheimer/inducido químicamente , Enfermedad de Alzheimer/patología , Secretasas de la Proteína Precursora del Amiloide/metabolismo , Péptidos beta-Amiloides/administración & dosificación , Animales , Ácido Aspártico Endopeptidasas/metabolismo , Western Blotting , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Región CA1 Hipocampal/metabolismo , Calcineurina/sangre , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/metabolismo , Enfermedad Crónica , Depresión/genética , Depresión/fisiopatología , Fenómenos Electrofisiológicos , Hipocampo/patología , Bombas de Infusión Implantables , Masculino , Fragmentos de Péptidos/administración & dosificación , Ratas , Ratas Wistar , Riesgo , Estrés Psicológico/genética , Estrés Psicológico/fisiopatología , Transmisión SinápticaRESUMEN
It is well known that caffeine and sleep deprivation have opposing effects on learning and memory; therefore, this study was undertaken to determine the effects of chronic (4wks) caffeine treatment (0.3g/l in drinking water) on long-term memory deficit associated with 24h sleep deprivation. Animals were sleep deprived using the modified multiple platform method. The results showed that chronic caffeine treatment prevented the impairment of long-term memory as measured by performance in the radial arm water maze task and normalized L-LTP in area CA1 of the hippocampi of sleep-deprived anesthetized rats. Sleep deprivation prevents the high frequency stimulation-induced increases in the levels of phosphorylated-cAMP response element binding protein (P-CREB) and brain-derived neurotrophic factor (BDNF) seen during the expression of late phase long-term potentiation (L-LTP). However, chronic caffeine treatment prevented the effect of sleep-deprivation on the stimulated levels of P-CREB and BDNF. The results suggest that chronic caffeine treatment may protect the sleep-deprived brain probably by preserving the levels of P-CREB and BDNF.
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Factor Neurotrófico Derivado del Encéfalo/metabolismo , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Cafeína/farmacología , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Memoria/efectos de los fármacos , Privación de Sueño/fisiopatología , Animales , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/genética , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Humanos , Potenciación a Largo Plazo/efectos de los fármacos , Potenciación a Largo Plazo/fisiología , Masculino , Trastornos de la Memoria/etiología , Fosforilación , Ratas , Ratas Wistar , Privación de Sueño/complicacionesRESUMEN
STUDY OBJECTIVES: This study was undertaken to provide a detailed account of the effect of chronic treatment with a small dose of caffeine on the deleterious effects of sleep loss on brain function in rats. EXPERIMENTAL DESIGN: We investigated the effects of chronic (4 weeks) caffeine treatment (0.3 g/L in drinking water) on memory impairment in acutely (24 h) sleep-deprived adult male Wistar rats. Sleep deprivation was induced using the modified multiple platform model. The effects of caffeine on sleep deprivation-induced hippocampus-dependent learning and memory deficits were studied by 3 approaches: learning and memory performance in the radial arm water maze task, electrophysiological recording of early long-term potentiation (E-LTP) in area CA1 of the hippocampus, and levels of memory- and synaptic plasticity-related signaling molecules after E-LTP induction. MEASUREMENT AND RESULTS: The results showed that chronic caffeine treatment prevented impairment of hippocampus-dependent learning, shortterm memory and E-LTP of area CA1 in the sleep-deprived rats. In correlation, chronic caffeine treatment prevented sleep deprivation-associated decrease in the levels of phosphorylated calcium/calmodulin-dependent protein kinase II (P-CaMKII) during expression of E-LTP. CONCLUSIONS: The results suggest that long-term use of a low dose of caffeine prevents impairment of short-term memory and E-LTP in acutely sleep-deprived rats.
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Cafeína/farmacología , Estimulantes del Sistema Nervioso Central/farmacología , Trastornos del Conocimiento/prevención & control , Plasticidad Neuronal/efectos de los fármacos , Privación de Sueño/complicaciones , Sinapsis/efectos de los fármacos , Animales , Conducta Animal/efectos de los fármacos , Cafeína/administración & dosificación , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/sangre , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/efectos de los fármacos , Estimulantes del Sistema Nervioso Central/administración & dosificación , Trastornos del Conocimiento/etiología , Modelos Animales de Enfermedad , Fenómenos Electrofisiológicos/efectos de los fármacos , Hipocampo/efectos de los fármacos , Aprendizaje/efectos de los fármacos , Potenciación a Largo Plazo/efectos de los fármacos , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Memoria a Corto Plazo/efectos de los fármacos , Ratas , Ratas Wistar , Análisis y Desempeño de TareasRESUMEN
We have previously reported that caffeine prevented sleep deprivation-induced impairment of long-term potentiation (LTP) of area CA1 as well as hippocampus-dependent learning and memory performance in the radial arm water maze. In this report we examined the impact of long-term (4-week) caffeine consumption (0.3 g/L in drinking water) on synaptic plasticity (Alhaider et al., 2010) deficit in the dentate gyrus (DG) area of acutely sleep-deprived rats. The sleep deprivation and caffeine/sleep deprivation groups were sleep-deprived for 24 h by using the columns-in-water technique. We tested the effect of caffeine and/or sleep deprivation on LTP and measured the basal levels as well as stimulated levels of LTP-related molecules in the DG. The results showed that chronic caffeine administration prevented the impairment of early-phase LTP (E-LTP) in the DG of sleep-deprived rats. Additionally, chronic caffeine treatment prevented the sleep deprivation-associated decreases in the basal levels of the phosphorylated calcium/calmodulin-dependent protein kinase II (P-CaMKII) and brain derived neurotrophic factor (BDNF) as well as in the stimulated levels of P-CaMKII in the DG area. The results suggest that chronic use of caffeine prevented anomalous changes in the basal levels of P-CaMKII and BDNF associated with sleep deprivation and as a result contributes to the revival of LTP in the DG region.