Exendin-(9-39) is an inverse agonist of the murine glucagon-like peptide-1 receptor: implications for basal intracellular cyclic adenosine 3',5'-monophosphate levels and beta-cell glucose competence.

The effect of exendin-(9-39), a described antagonist of the glucagon-like peptide-1 (GLP-1) receptor, was evaluated on the formation of cAMP- and glucose-stimulated insulin secretion (GSIS) by the conditionally immortalized murine betaTC-Tet cells. These cells have a basal intracellular cAMP level that can be increased by GLP-1 with an EC50 of approximately 1 nM and can be decreased dose dependently by exendin-(9-39). This latter effect was receptor dependent, as a beta-cell line not expressing the GLP-1 receptor was not affected by exendin-(9-39). It was also not due to the endogenous production of GLP-1, because this effect was observed in the absence of detectable preproglucagon messenger RNA levels and radioimmunoassayable GLP-1. Importantly, GSIS was shown to be sensitive to this basal level of cAMP, as perifusion of betaTC-Tet cells in the presence of exendin-(9-39) strongly reduced insulin secretion. This reduction of GSIS, however, was observed only with growth-arrested, not proliferating, betaTC-Tet cells; it was also seen with nontransformed mouse beta-cells perifused in similar conditions. These data therefore demonstrated that 1) exendin-(9-39) is an inverse agonist of the murine GLP-1 receptor; 2) the decreased basal cAMP levels induced by this peptide inhibit the secretory response of betaTC-Tet cells and mouse pancreatic islets to glucose; 3) as this effect was observed only with growth-arrested cells, this indicates that the mechanism by which cAMP leads to potentiation of insulin secretion is different in proliferating and growth-arrested cells; and 4) the presence of the GLP-1 receptor, even in the absence of bound peptide, is important for maintaining elevated intracellular cAMP levels and, therefore, the glucose competence of the beta-cells.

Astressin B, a nonselective corticotropin-releasing hormone receptor antagonist, prevents the inhibitory effect of ghrelin on luteinizing hormone pulse frequency in the ovariectomized rhesus monkey.

Administration of ghrelin, a key peptide in the regulation of energy homeostasis, has been shown to decrease LH pulse frequency while concomitantly elevating cortisol levels. Because increased endogenous CRH release in stress is associated with an inhibition of reproductive function, we have tested here whether the pulsatile LH decrease after ghrelin may reflect an activated hypothalamic-pituitary-adrenal axis and be prevented by a CRH antagonist. After a 3-h baseline LH pulse frequency monitoring, five adult ovariectomized rhesus monkeys received a 5-h saline (protocol 1) or ghrelin (100-microg bolus followed by 100 microg/h, protocol 2) infusion. In protocols 3 and 4, animals were given astressin B, a nonspecific CRH receptor antagonist (0.45 mg/kg im) 90 min before ghrelin or saline infusion. Blood samples were taken every 15 min for LH measurements, whereas cortisol and GH were measured every 45 min. Mean LH pulse frequency during the 5-h ghrelin infusion was significantly lower than in all other treatments (P < 0.05) and when compared with the baseline period (P < 0.05). Pretreatment with astressin B prevented the decrease. Ghrelin stimulated cortisol and GH secretion, whereas astressin B pretreatment prevented the cortisol, but not the GH, release. Our data indicate that CRH release mediates the inhibitory effect of ghrelin on LH pulse frequency and suggest that the inhibitory impact of an insufficient energy balance on reproductive function may in part be mediated by the hypothalamic-pituitary-adrenal axis.

Effects of dexamethasone on hepatic glucose production and fructose metabolism in healthy humans.

This study was designed to determine whether glucocorticoids alter autoregulation of glucose production and fructose metabolism. Two protocols with either dexamethasone (DEX) or placebo (Placebo) were performed in six healthy men during hourly ingestion of[13C]fructose (1.33 mmol.kg-1.h-1) for 3 h. In both protocols, endogenous glucose production (EGP) increased by 8 (Placebo) and 7% (DEX) after fructose, whereas gluconeogenesis from fructose represented 82 (Placebo) and 72% (DEX) of EGP. Fructose oxidation measured from breath 13CO2 was similar in both protocols [9.3 +/- 0.7 (Placebo) and 9.6 +/- 0.5 mumol.kg-1.min-1 (DEX)]. Nonoxidative carbohydrate disposal, calculated as fructose administration rate minus net carbohydrate oxidation rate after fructose ingestion measured by indirect calorimetry, was also similar in both protocols [5.8 +/- 0.8 (Placebo) and 5.9 +/- 2.0 mumol.kg-1.min-1 (DEX)]. We concluded that dexamethasone 1) does not alter the autoregulatory process that prevents a fructose-induced increase in gluconeogenesis from increasing total glucose production and 2) does not affect oxidative and nonoxidative pathways of fructose. This indicates that the insulin-regulated enzymes involved in these pathways are not affected in a major way by dexamethasone.

Nosocomial nontyphoidal salmonellosis after antineoplastic chemotherapy : reactivation of asymptomatic colonization ?

Abstract An increased frequency of nontyphoidal salmonellosis is well established in cancer patients, but it is unclear whether this represents increased susceptibility to exogenous infection or opportunistic, endogenous reactivation of asymptomatic carriage. In a retrospective study, a simple case definition was used to identify the probable presence of reactivation salmonellosis in five cancer patients between 1996 and 2002. Reactivation salmonellosis was defined as the development of nosocomial diarrhea >72 h after admission and following the administration of antineoplastic chemotherapy in an HIV-seronegative cancer patient who was asymptomatic on admission, in the absence of epidemiological evidence of a nosocomial outbreak. Primary salmonellosis associated with unrecognized nosocomial transmission or community acquisition and an unusually prolonged incubation period could not entirely be ruled out. During the same time period, another opportunistic infection, Pneumocystis pneumonia, was diagnosed in six cancer patients. Presumably, asymptomatic intestinal Salmonella colonization was converted to invasive infection by chemotherapy-associated intestinal mucosal damage and altered innate immune mechanisms. According to published guidelines, stool specimens from patients hospitalized for longer than 72 h should be rejected unless the patient is neutropenic or ≥65 years old with significant comorbidity. However, in this study neutropenia was present in only one patient, and four patients were <65 years old. Guidelines should thus be revised in order not to reject stool culture specimens from such patients. In cancer patients, nosocomial salmonellosis can Occur as a chemo-therapy-triggered opportunistic reactivation infection that may be similar in frequency to Pneumocystis pneumonia.

Analysis of c-Myc function in mouse epidermis

Abstract The c-myc gene is one of the most frequently mutated oncogenes found in human tumors. c-Myc has been implicated in the regulation of various biological processes including cell cycle progression, cellular growth, differentiation, angiogenesis, immortalization and apoptosis. To assess the normal role of c-Myc in epithelial cell types in vitro and in vivo we have deleted the c-myc gene in keratinocytes and in the adult skin epidermis by conditional Cre/loxP mediated recombination. Similar to what we have previously shown in mouse embryonic fibroblasts acute elimination of c-Myc activity in cultured keratinocytes causes cells to cease proliferation and adapt a flat cell morphology. Mutant cells accumulate in a diploid Ki67neg stage, indicative of a quiescent Go stage. This demonstrates that c-Myc activity is essential to maintain keratinocytes in a productive cell cycle. In addition, mutant keratinocytes showed a defect in Ca2+ induced induction of the differentiation marker Keratin 1 suggesting a role for c-Myc during differentiation. To assess the in vivo role of c-Myc we used a tamoxifen inducible K5::CreERT transgene to delete the c-myc gene in the adult skin epidermis. Unexpectedly, despite strong c-Myc expression in the basal compartment it is not required for maintenance of the skin epidermis in the adult mouse. The epidermis appeared normal with respect to both proliferation and differentiation. In addition, no selection against c-Myc deficient epidermal cells occurred over many months, further confirming that c-Myc is dispensable for normal skin homeostasis. Even more surprising, TPA induced hyperproliferation also occurred in a c-Myc independent manner. Treatment of the skin with the mutagen DMBA prior to TPA is a classical way to induce papillomas by selecting for mutations that lead to dominant activation of the oncogene Ha-Ras. Most interestingly tumor formation was severely inhibited suggesting that tumor progression requires endogenous c-Myc. Further studies are required to address whether the role of c-Myc in the activation of telomerase or the Werner protein, or its role to induce angiogenesis is required for skin tumor progression, In conclusion, this work shows that while c-Myc is not required for maintenance or hyperplasia of mouse epidermis, it is essential for skin tumor progression in collaboration with Ras. Résumé Le gène c-myc est un des oncogènes les plus fréquemment mutés dans les tumeurs humaines. c-Myc est impliqué dans la régulation de processus biologiques variés, comme la progression du cycle cellulaire, la croissance cellulaire, la différenciation, l'angiogenèse, l'immortalisation et l'apoptose. Pour caractériser le rôle physiologique de c-Myc dans les cellules de type épithélial in vitro et in vivo, le gène c-myc a été délété dans des kératinocytes primaires et dans l'épiderme de peau de souris adultes par des recombinaisons conditionnelles (système Cre/loxP). De la même façon que dans les fibroblastes d'embryon de souris, l'élimination aiguë de l'activité de c-Myc dans les kératinocytes en culture primaire provoque l'arrêt de la prolifération des cellules et leur applatissement morphologique. Les cellules mutantes restent dans un stade diploïde Ki67neg, indiquant un stade quiescent Go. Cela démontre que l'activité de c-Myc est essentielle pour maintenir les kératinocytes dans le cycle cellulaire. De plus, les kératinocytes mutants montrent une déficience pour le marqueur de différenciation Kératine 1 au cours de la différenciation induite par le calcium, suggérant un rôle de c-Myc dans la différenciation cellulaire. Pour comprendre le rôle de c-Myc in vivo, le transgène K5::CreERT inductible par le tamoxifen a été utilisé pour déléter le gène c-inyc dans l'épiderme de souris adultes. Etonnemment, malgré une forte expression de c-Myc dans le compartiment basal de l'épiderme, ce gène n'est pas nécessaire pour la maintenance de l'épiderme de la peau chez la souris adulte. L'épiderme apparait normal avec une prolifération et une différenciation physiologique des cellules. De plus, il n'y a pas de sélection contre les cellules épidennales c-Myc déficientes après plusieurs mois, ce qui confirme que c-Myc n'est pas nécessaire pour l'homéostasie normale de la peau. Encore plus surprenant, une hyperprolifération est également induite par du TPA chez les souris mutantes, impliquant une voie de prolifération indépendante de c-Myc. Le traitement de la peau par le mutagène DMBA avant le traitement au TPA est une voie classique d'induction de papillomes, par sélection de mutations conduisant à l'activation de l'oncogène Ha-Ras. La formation des tumeurs est fortement inhibée chez les souris mutantes, suggérant que la progression des tumeurs nécessite la présence endogène de c-Myc. De nouvelles études sont nécessaires pour savoir si c-Myc a un rôle dans l'activation de la télomérase ou de la protéine de Werner, ou encore dans l'angiogénèse, qui sont nécessaires pour la progression tumorale. En conclusion, ce travail montre que même si c-Myc n'est pas nécessaire pour la maintenance ou l'hyperplasie de la peau de souris, il est essentiel pour la progression des tumeurs de la peau en collaboration avec Ras.

Ghrelin-induced orexigenic effect in rats depends on the metabolic status and is counteracted by peripheral CB1 receptor antagonism.

Ghrelin is an endogenous regulator of energy homeostasis synthesized by the stomach to stimulate appetite and positive energy balance. Similarly, the endocannabinoid system is part of our internal machinery controlling food intake and energy expenditure. Both peripheral and central mechanisms regulate CB1-mediated control of food intake and a functional relationship between hypothalamic ghrelin and cannabinoid CB1 receptor has been proposed. First of all, we investigated brain ghrelin actions on food intake in rats with different metabolic status (negative or equilibrate energy balance). Secondly, we tested a sub-anxiogenic ultra-low dose of the CB1 antagonist SR141716A (Rimonabant) and the peripheral-acting CB1 antagonist LH-21 on ghrelin orexigenic actions. We found that: 1) central administration of ghrelin promotes food intake in free feeding animals but not in 24 h food-deprived or chronically food-restricted animals; 2) an ultra-low dose of SR141716A (a subthreshold dose 75 folds lower than the EC50 for induction of anxiety) completely counteracts the orexigenic actions of central ghrelin in free feeding animals; 3) the peripheral-restricted CB1 antagonist LH-21 blocks ghrelin-induced hyperphagia in free feeding animals. Our study highlights the importance of the animaĺs metabolic status for the effectiveness of ghrelin in promoting feeding, and suggests that the peripheral endocannabinoid system may interact with ghrelińs signal in the control of food intake under equilibrate energy balance conditions.

Navigator-gated coronary magnetic resonance angiography using steady-state-free-precession: comparison to standard T2-prepared gradient-echo and spiral imaging.

RATIONALE AND OBJECTIVES: Recent developments of magnetic resonance imaging enabled free-breathing coronary MRA (cMRA) using steady-state-free-precession (SSFP) for endogenous contrast. The purpose of this study was a systematic comparison of SSFP cMRA with standard T2-prepared gradient-echo and spiral cMRA. METHODS: Navigator-gated free-breathing T2-prepared SSFP-, T2-prepared gradient-echo- and T2-prepared spiral cMRA was performed in 18 healthy swine (45-68 kg body-weight). Image quality was investigated subjectively and signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR) and vessel sharpness were compared. RESULTS: SSFP cMRA allowed for high quality cMRA during free breathing with substantial improvements in SNR, CNR and vessel sharpness when compared with standard T2-prepared gradient-echo imaging. Spiral imaging demonstrated the highest SNR while image quality score and vessel definition was best for SSFP imaging. CONCLUSION: Navigator-gated free-breathing T2-prepared SSFP cMRA is a promising new imaging approach for high signal and high contrast imaging of the coronary arteries with improved vessel border definition.

Stable carbon isotope composition of perirenal adipose tissue fatty acids from Engadine sheep grazing either mountain or lowland pasture

To provide further insights into ruminant lipid digestion and metabolism, and into cis9, trans-11 18:2 synthesis, 12 growing Engadine lambs grazing either mountain pasture (2,250 m above sea level; n = 6) or lowland pasture (400 m above sea level; n = 6) were studied. Both pastures consisted exclusively of C-3 plants. Before the experiment, all animals grazed a common pasture for 6 wk. Grasses and perirenal adipose tissues of the sheep were analyzed for fatty acids by gas chromatography. Stable C-isotope ratios (delta C-13 values in % vs. the Vienna Pee Dee Belemnite standard) were determined in the composite samples by elemental analysis-isotope ratio mass spectrometry. The delta C-13 of the individual fatty acids were measured by gas chromatography-combustion-isotope ratio mass spectrometry. The delta C-13 value of the entire mountain pasture grass was -27.5% (SD 0.31), whereas that of the lowland pasture grass was -30.0% (SD 0.07). This difference was reflected in the perirenal adipose tissues of the corresponding sheep (P < 0.05), even though the delta C-13 values were less in the animals than in the grass. The delta C-13 values for cis-9 16:1 and cis-9 18:1 in perirenal fat differed between mountain and lowland lambs (P < 0.05). The 16:0 in the adipose tissue was enriched in C-13 by 5% compared with the dietary 16:0, likely as a result of partly endogenous synthesis. The d13C values of cis-9, trans-11 18:2 (cis-9, trans-11 CLA) in the adipose tissue were smaller than those of its dietary precursors, cis-9, cis-12 18:2 and cis-9, cis-12, cis-15 18:3; conversely, the delta C-13 values of trans-11 18:1 were not, suggesting that large proportions of perirenal cis-9, trans-11 18:2 were of endogenous origin and discrimination against C-13 occurred during Delta(9)-desaturation. The same discrimination was indicated by the isotopic shift between 16:0 and cis-9 16:1 in the mountain grazing group. Furthermore, the delta C-13 values of cis-9, trans-11 18:2 were smaller relative to the precursor fatty acids in the mountain lambs compared with the lowland group. This result suggests a reduced extent of biohydrogenation in lambs grazing on mountain grass in comparison with those grazing on lowland grass. This was supported by the smaller cis-9, trans-11 18:2 concentrations in total fatty acids found in the adipose tissues of the lowland lambs (P < 0.001). The results of this study demonstrate that natural differences between delta C-13 values of swards from different pastures and the adipose tissue fatty acids could be used as tracers in studies of lipid metabolism in ruminants.

Circadian rhythms in insect disease vectors

Organisms from bacteria to humans have evolved under predictable daily environmental cycles owing to the Earth’s rotation. This strong selection pressure has generated endogenous circadian clocks that regulate many aspects of behaviour, physiology and metabolism, anticipating and synchronising internal time-keeping to changes in the cyclical environment. In haematophagous insect vectors the circadian clock coordinates feeding activity, which is important for the dynamics of pathogen transmission. We have recently witnessed a substantial advance in molecular studies of circadian clocks in insect vector species that has consolidated behavioural data collected over many years, which provided insights into the regulation of the clock in the wild. Next generation sequencing technologies will facilitate the study of vector genomes/transcriptomes both among and within species and illuminate some of the species-specific patterns of adaptive circadian phenotypes that are observed in the field and in the laboratory. In this review we will explore these recent findings and attempt to identify potential areas for further investigation.

Stringent V beta requirement for the development of NK1.1+ T cell receptor-alpha/beta+ cells in mouse liver.

The liver of C57BL/6 mice contains a major subset of CD4+8- and CD4-8- T cell receptor (TCR)-alpha/beta+ cells expressing the polymorphic natural killer NK1.1 surface marker. Liver NK1.1+TCR-alpha/beta+ (NK1+ T) cells require interaction with beta2-microglobulin-associated, major histocompatibility complex I-like molecules on hematopoietic cells for their development and have a TCR repertoire that is highly skewed to Vbeta8.2, Vbeta7, and Vbeta2. We show here that congenic C57BL/6.Vbeta(a) mice, which lack Vbeta8- expressing T cells owing to a genomic deletion at the Vbeta locus, maintain normal levels of liver NK1+ T cells owing to a dramatic increase in the proportion of cells expressing Vbeta7 and Vbeta2 (but not other Vbetas). Moreover, in C57BL/6 congenic TCR-V Vbeta3 and -Vbeta8.1 transgenic mice (which in theory should not express other Vbeta, owing to allelic exclusion at the TCR-beta locus), endogenous TCR-Vbeta8.2, Vbeta7, and Vbeta2 (but not other Vbetas) are frequently expressed on liver NK1+T cells but absent on lymph node T cells. Finally, when endogenous V beta expression is prevented in TCR-Vbeta3 and Vbeta8.1 transgenic mice (by introduction of a null allele at the C beta locus), the development of liver NK1+T cells is totally abrogated. Collectively, our data indicate that liver NK1+T cells have a stringent requirement for expression of TCR-Vbeta8.2, Vbeta7, or Vbeta2 for their development.

Leontief versus Ghosh: two faces of the same coin

In this paper we explore the sectoral and aggregate implications of some endogeneization rules (i.e. on value-added and final demand) which have been common in the Leontief model and have been recently proposed in the Ghosh model. We detect that these rules may give rise in both models to some allegedly pathological behavior in the sense that sectoral or aggregate output, very often, may not follow the logical and economically expected direct relationship with some underlying endogenous variables—namely, output and value-added in the Ghosh model and output and consumption in the Leontief model. Because of the common mathematical structure, whatever is or seems to be pathological in the Ghosh model also has a symmetric counterpart in the Leontief model. These would not be good news for the inner consistency of these linear models. To avoid such possible inconsistencies, we propose new and simple endogeneization rules that have a sound economic interpretation.

Molecular epidemiology of Candida albicans and Candida glabrata strains isolated from intensive care unit patients in Poland

Over the last decades, Candida spp have been responsible for an increasing number of infections, especially in patients requiring intensive care. Knowledge of local epidemiology and analysis of the spread of these pathogens is important in understanding and controlling their transmission. The aim of this study was to evaluate the genetic diversity of 31 Candida albicans and 17 Candida glabrata isolates recovered from intensive care unit patients from the tertiary hospital in Krakow between 2011-2012. The strains were typed by random amplified polymorphic DNA (RAPD) polymerase chain reaction using five primers (CD16AS, HP1247, ERIC-2, OPE-3 and OPE-18). The results of the present investigation revealed a high degree of genetic diversity among the isolates. No clonal relationship was found among the C. albicans strains, whereas two C. glabrata isolates were identical. The source of Candida infection appeared to be mostly endogenous; however, the presence of two clonal C. glabrata strains suggested the possibility of cross-transmission of these pathogens. Our study confirmed the high discriminatory power of the RAPD technique in the molecular typing of Candida clinical isolates. This method may be applied to the evaluation of transmission routes of pathogenic fungi on a local level.

5

Retinoid X Receptors (RXR) were initially identified as nuclear receptors binding with stereo-selectivity the vitamin A derivative 9-cis retinoic acid, although the relevance of this molecule as endogenous activator of RXRs is still elusive. Importantly, within the nuclear receptor superfamily, RXRs occupy a peculiar place, as they are obligatory partners for a number of other nuclear receptors, thus integrating the corresponding signaling pathways. In this chapter, we describe the structural features allowing RXR to form homo- and heterodimers, and the functional consequences of this unique ability. Furthermore, we discuss the importance of studying RXR activity at a genome-wide level in order to comprehensively address the biological implications of their action that is fundamental to understand to what extent RXRs could be exploited as new therapeutic targets.

Pharmacological blockade of either cannabinoid CB1 or CB2 receptors prevents both cocaine-induced conditioned locomotion and cocaine-induced reduction of cell proliferation in the hippocampus of adult male rat.

Addiction to major drugs of abuse, such as cocaine, has recently been linked to alterations in adult neurogenesis in the hippocampus. The endogenous cannabinoid system modulates this proliferative response as demonstrated by the finding that pharmacological activation/blockade of cannabinoid CB1 and CB2 receptors not only modulates neurogenesis but also modulates cell death in the brain. In the present study, we evaluated whether the endogenous cannabinoid system affects cocaine-induced alterations in cell proliferation. To this end, we examined whether pharmacological blockade of either CB1 (Rimonabant, 3 mg/kg) or CB2 receptors (AM630, 3 mg/kg) would affect cell proliferation [the cells were labeled with 5-bromo-2'-deoxyuridine (BrdU)] in the subventricular zone (SVZ) of the lateral ventricle and the dentate subgranular zone (SGZ). Additionally, we measured cell apoptosis (as monitored by the expression of cleaved caspase-3) and glial activation [by analyzing the expression of glial fibrillary acidic protein (GFAP) and Iba-1] in the striatum and hippocampus during acute and repeated (4 days) cocaine administration (20 mg/kg). The results showed that acute cocaine exposure decreased the number of BrdU-immunoreactive (ir) cells in the SVZ and SGZ. In contrast, repeated cocaine exposure reduced the number of BrdU-ir cells only in the SVZ. Both acute and repeated cocaine exposure increased the number of cleaved caspase-3-, GFAP- and Iba1-ir cells in the hippocampus, and this effect was counteracted by AM630 or Rimonabant, which increased the number of BrdU-, GFAP-, and Iba1-ir cells in the hippocampus. These results indicate that the changes in neurogenic, apoptotic and gliotic processes that were produced by repeated cocaine administration were normalized by pharmacological blockade of CB1 and CB2. The restorative effects of cannabinoid receptor blockade on hippocampal cell proliferation were associated with the prevention of the induction of conditioned locomotion but not with the prevention of cocaine-induced sensitization.

Localization of peroxisome proliferator-activated receptor alpha (PPARα) and N-acyl phosphatidylethanolamine phospholipase D (NAPE-PLD) in cells expressing the Ca(2+)-binding proteins calbindin, calretinin, and parvalbumin in the adult rat hippocampus.

The N-acylethanolamines (NAEs), oleoylethanolamide (OEA) and palmithylethanolamide (PEA) are known to be endogenous ligands of PPARα receptors, and their presence requires the activation of a specific phospholipase D (NAPE-PLD) associated with intracellular Ca(2+) fluxes. Thus, the identification of a specific population of NAPE-PLD/PPARα-containing neurons that express selective Ca(2+)-binding proteins (CaBPs) may provide a neuroanatomical basis to better understand the PPARα system in the brain. For this purpose, we used double-label immunofluorescence and confocal laser scanning microscopy for the characterization of the co-existence of NAPE-PLD/PPARα and the CaBPs calbindin D28k, calretinin and parvalbumin in the rat hippocampus. PPARα expression was specifically localized in the cell nucleus and, occasionally, in the cytoplasm of the principal cells (dentate granular and CA pyramidal cells) and some non-principal cells of the hippocampus. PPARα was expressed in the calbindin-containing cells of the granular cell layer of the dentate gyrus (DG) and the SP of CA1. These principal PPARα(+)/calbindin(+) cells were closely surrounded by NAPE-PLD(+) fiber varicosities. No pyramidal PPARα(+)/calbindin(+) cells were detected in CA3. Most cells containing parvalbumin expressed both NAPE-PLD and PPARα in the principal layers of the DG and CA1/3. A small number of cells containing PPARα and calretinin was found along the hippocampus. Scattered NAPE-PLD(+)/calretinin(+) cells were specifically detected in CA3. NAPE-PLD(+) puncta surrounded the calretinin(+) cells localized in the principal cells of the DG and CA1. The identification of the hippocampal subpopulations of NAPE-PLD/PPARα-containing neurons that express selective CaBPs should be considered when analyzing the role of NAEs/PPARα-signaling system in the regulation of hippocampal functions.