Is an oropharyngeal HPV infection more frequently detectable in women with a genital HPV infection?

PURPOSE: If not eliminated by the immune system and persisting over years, oropharyngeal high-risk HPV infection can lead to cancer development in the oropharynx. HPV infection is very commonly found in the genital region and can serve as an HPV reservoir. In this study, we investigate whether women with a genital HPV infection are at a higher risk of harboring an undetected oropharyngeal HPV infection via genital-oropharyngeal transmission. METHODS: Women presenting for routine gynecological checkups were included in this study. All participants received an HPV brush test from the genital region as well as from the oropharynx. Additionally, probable risk factors for an HPV infection were assessed in a structured questionnaire. RESULTS: 142 women were included in this study. The rate of oropharyngeal HPV infection was low with 2/142 (1,4%) women positive for a low-risk HPV genotype. In the genital brush test, 54/142 (38%) women were tested HPV positive of which 41/142 (29%) were positive for a high-risk HPV genotype. CONCLUSIONS: The rate of an oropharyngeal HPV detection in our population was low with 2/142 women harboring a low-risk HPV infection.

Ageing is associated with a reduction in markers of mitochondrial energy metabolism in the human epidermis.

The decline of mitochondrial function throughout the lifespan is directly linked to the development of ageing phenotypes of the skin. Here, we assessed alterations in markers of epidermal mitochondrial energy metabolism as a function of skin age. Human skin samples from distinct anatomical regions were obtained during routine dermatological surgery from 21 young (27.6 ± 1.71 year) and 22 old (76.2 ± 1.73 year) donors. Sections of skin samples were analysed by immunohistochemistry for mitochondrial subunits of each electron transport chain complex (I-V)/oxidative phosphorylation (OXPHOS), as well as proteins serving as a marker of mitochondrial mass (VDAC1) and the regulation of DNA transcription (TFAM). Staining intensities of ATP5F1A (comprising complex V) and TFAM in the epidermis of older subjects were significantly decreased compared with younger donors. Moreover, these effects were independent of UV exposure of the stained skin section. Overall, we demonstrate that ageing is associated with reduced protein levels of complex V of the mitochondrial respiratory chain and TFAM. These alterations may impair essential mitochondrial functions, exacerbating the cutaneous ageing process.

Galanin 2 Receptor: A Novel Target for a Subset of Pancreatic Ductal Adenocarcinoma.

Galanin is a 30 amino acid peptide that stimulates three subtype receptors (GAL1-3R). M89b is a lanthionine-stabilized, C-terminally truncated galanin analog that specifically stimulates GAL2R. We investigated the potential of M89b as a therapeutic for pancreatic ductal adenocarcinoma (PDAC) and assessed its safety. The anti-tumor activity of subcutaneously injected M89b on the growth of patient-derived xenografts of PDAC (PDAC-PDX) in mice was investigated. In addition, the safety of M89b was assessed in vitro using a multi-target panel to measure the off-target binding and modulation of enzyme activities. In a PDAC-PDX with a high GAL2R expression, M89b completely inhibited the growth of the tumor (p < 0.001), while in two PDAC-PDXs with low GAL2R expression, low or negligeable inhibition of tumor growth was measured, and in the PDX without GAL2R expression no influence on the tumor growth was observed. The M89b treatment of the GAL2R high-PDAC-PDX-bearing mice led to a reduction in the expression of RacGap1 (p < 0.05), PCNA (p < 0.01), and MMP13 (p < 0.05). In vitro studies involving a multi-target panel of pharmacologically relevant targets revealedexcellent safety of M89b. Our data indicated that GAL2R is a safe and valuable target for treating PDACs with high GAL2R expression.

Topical Diacerein Decreases Skin and Splenic CD11c+ Dendritic Cells in Psoriasis.

Psoriasis is an inflammatory skin disease characterized by increased neo-vascularization, keratinocyte hyperproliferation, a pro-inflammatory cytokine milieu and immune cell infiltration. Diacerein is an anti-inflammatory drug, modulating immune cell functions, including expression and production of cytokines, in different inflammatory conditions. Therefore, we hypothesized that topical diacerein has beneficial effects on the course of psoriasis. The current study aimed to evaluate the effect of topical diacerein on imiquimod (IMQ)-induced psoriasis in C57BL/6 mice. Topical diacerein was observed to be safe without any adverse side effects in healthy or psoriatic animals. Our results demonstrated that diacerein significantly alleviated the psoriasiform-like skin inflammation over a 7-day period. Furthermore, diacerein significantly diminished the psoriasis-associated splenomegaly, indicating a systemic effect of the drug. Remarkably, we observed significantly reduced infiltration of CD11c+ dendritic cells (DCs) into the skin and spleen of psoriatic mice with diacerein treatment. As CD11c+ DCs play a pivotal role in psoriasis pathology, we consider diacerein to be a promising novel therapeutic candidate for psoriasis.

From old to new - Repurposing drugs to target mitochondrial energy metabolism in cancer.

Although we have entered the era of personalized medicine and tailored therapies, drugs that target a large variety of cancers regardless of individual patient differences would be a major advance nonetheless. This review article summarizes current concepts and therapeutic opportunities in the area of targeting aerobic mitochondrial energy metabolism in cancer. Old drugs previously used for diseases other than cancer, such as antibiotics and antidiabetics, have the potential to inhibit the growth of various tumor entities. Many drugs are reported to influence mitochondrial metabolism. However, here we consider only those drugs which predominantly inhibit oxidative phosphorylation.

Dietary restriction in senolysis and prevention and treatment of disease.

Aging represents a key risk factor for a plethora of diseases. Targeting detrimental processes which occur during aging, especially before onset of age-related disease, could provide drastic improvements in healthspan. There is increasing evidence that dietary restriction (DR), including caloric restriction, fasting, or fasting-mimicking diets, extend both lifespan and healthspan. This has sparked interest in the use of dietary regimens as a non-pharmacological means to slow aging and prevent disease. Here, we review the current evidence on the molecular mechanisms underlying DR-induced health improvements, including removal of senescent cells, metabolic reprogramming, and epigenetic rejuvenation.

Epigenetic and metabolic regulation of epidermal homeostasis.

Continuous exposure of the skin to environmental, mechanical and chemical stress necessitates constant self-renewal of the epidermis to maintain its barrier function. This self-renewal ability is attributed to epidermal stem cells (EPSCs), which are long-lived, multipotent cells located in the basal layer of the epidermis. Epidermal homeostasis - coordinated proliferation and differentiation of EPSCs - relies on fine-tuned adaptations in gene expression which in turn are tightly associated with specific epigenetic signatures and metabolic requirements. In this review, we will briefly summarize basic concepts of EPSC biology and epigenetic regulation with relevance to epidermal homeostasis. We will highlight the intricate interplay between mitochondrial energy metabolism and epigenetic events - including miRNA-mediated mechanisms - and discuss how the loss of epigenetic regulation and epidermal homeostasis manifests in skin disease. Discussion of inherited epidermolysis bullosa (EB) and disorders of cornification will focus on evidence for epigenetic deregulation and failure in epidermal homeostasis, including stem cell exhaustion and signs of premature ageing. We reason that the epigenetic and metabolic component of epidermal homeostasis is significant and warrants close attention. Charting epigenetic and metabolic complexities also represents an important step in the development of future systemic interventions aimed at restoring epidermal homeostasis and ameliorating disease burden in severe skin conditions.

A magnet attached to the forehead disrupts magnetic compass orientation in a migratory songbird.

For studies on magnetic compass orientation and navigation performance in small bird species, controlled experiments with orientation cages inside an electromagnetic coil system are the most prominent methodological paradigm. These are, however, not applicable when studying larger bird species and/or orientation behaviour during free flight. For this, researchers have followed a very different approach, attaching small magnets to birds, with the intention of depriving them of access to meaningful magnetic information. Unfortunately, results from studies using this approach appear rather inconsistent. As these are based on experiments with birds under free-flight conditions, which usually do not allow exclusion of other potential orientation cues, an assessment of the overall efficacy of this approach is difficult to conduct. Here, we directly tested the efficacy of small magnets for temporarily disrupting magnetic compass orientation in small migratory songbirds using orientation cages under controlled experimental conditions. We found that birds which have access to the Earth's magnetic field as their sole orientation cue show a general orientation towards their seasonally appropriate migratory direction. When carrying magnets on their forehead under these conditions, the same birds become disoriented. However, under changed conditions that allow birds access to other (i.e. celestial) orientation cues, any disruptive effect of the magnets they carry appears obscured. Our results provide clear evidence for the efficacy of the magnet approach for temporarily disrupting magnetic compass orientation in birds, but also reveal its limitations for application in experiments under free-flight conditions.

Does low-level laser therapy affect the survival of patients with head and neck cancer?

Low-level laser therapy (LLLT) is used in patients with head and neck cancer (HNC) for treatment-related mucositis. There is conflicting evidence as to whether LLLT leads to the proliferation of tumor cells and whether it interferes with the tumoricidal effect of radiotherapy or chemoradiotherapy, if the tumor lies within the LLLT field. Using fuzzy matching, 126 HNC patients who had received LLLT including the tumor region and 126 matching HNC patients without LLLT (controls) treated at the Department of Otorhinolaryngology, Head & Neck Surgery, Medical University of Innsbruck, were identified. The overall survival was compared using the Kaplan-Meier analysis. Fuzzy matching yielded 2 patient samples well comparable in terms of risk of death. The survival did not significantly differ between patients with and without LLLT (p = 0.18). An increased risk of death in HNC patients who received LLLT covering the tumor region was not observed in our study.

Involvement of Neuropeptide Galanin Receptors 2 and 3 in Learning, Memory and Anxiety in Aging Mice.

The neuropeptide galanin (GAL), which is expressed in limbic brain structures, has a strong impact on the regulation of mood and behavior. GAL exerts its effects via three G protein-coupled receptors (GAL1-3-R). Little is known about the effects of aging and loss of GAL-Rs on hippocampal-mediated processes connected to neurogenesis, such as learning, memory recall and anxiety, and cell proliferation and survival in the dorsal dentate gyrus (dDG) in mice. Our results demonstrate that loss of GAL3-R, but not GAL2-R, slowed learning and induced anxiety in older (12-14-month-old) mice. Lack of GAL2-R increased cell survival (BrdU incorporation) in the dDG of young mice. However, normal neurogenesis was observed in vitro using neural stem and precursor cells obtained from GAL2-R and GAL3-R knockouts upon GAL treatment. Interestingly, we found sub-strain differences between C57BL/6J and C57BL/6N mice, the latter showing faster learning, less anxiety and lower cell survival in the dDG. We conclude that GAL-R signaling is involved in cognitive functions and can modulate the survival of cells in the neurogenic niche, which might lead to new therapeutic applications. Furthermore, we observed that the mouse sub-strain had a profound impact on the behavioral parameters analyzed and should therefore be carefully considered in future studies.

[Dynamic procedures for facial nerve reconstruction]. / Dynamische Verfahren zur Gesichtsnervenrekonstruktion.

In this article the indications and surgical treatment options for patients with facial nerve palsy are discussed. A distinction is made between static and dynamic surgical procedures. Static reconstructions for example are used to restore the eyelid closure function. For smile reconstruction, which is important for the psychosocial life of the patient, dynamic procedures are used. Depending on the duration of the facial nerve paralysis, there are several possibilities to restore the smile. In this work the masseteric branch transposition to the buccal branch, the hypoglossal-facial nerve anastomosis, the Labbé procedure and the gracilis flap as a free muscle transplant are discussed. The surgical procedures are compared and the advantages and disadvantages of the intervention are presented. A spontaneous smile is aimed, this cannot always be achieved. With the masseteric branch transposition to the buccal branch and the Labbé procedure the smile is initially triggered by chewing. A spontaneous smile is possible through cortical adaptation. With the gracilis flap, however, a nerve anastomosis with the contralateral 'healthy' facial nerve is possible, either directly or via a so-called cross facial nerve grafting, whereby a spontaneous smile can be achieved.

Nasal Floor Asymmetry Is Associated With Nasal Obstruction.

PURPOSE: The role of morphologic characteristics of the nasal cavity in nasal obstruction is not yet sufficiently understood. The aim of this study was to determine which morphometric parameters of the nasal cavity severely impair nasal breathing and when. PATIENTS AND METHODS: In a hospital-based, computed tomography-morphometric cross-sectional study, we evaluated computed tomography coronal scans of patients with known nasal obstruction scheduled to undergo functional nasal surgical procedures (cases) and trauma patients without facial involvement or known nasal obstruction (controls). The primary predictor variable was case versus control. In both groups, we measured and compared the piriform aperture width; nasal floor canting; piriform aperture vertical height, height-width ratio, and total cross-sectional area; height difference between the right and left nasal floors; and nasal septal thickness; as well as age and gender differences. Metric data means, standard deviations, and 95% confidence intervals were calculated and analyzed. RESULTS: The sample was composed of 60 patients evenly divided between cases and controls. Of these, 30 were men. The average age of the cases and controls was 27.4 ± 7.8 years and 38.5 ± 18.6 years, respectively (P < .001). The differences in piriform aperture width were not statistically significant between cases and controls (23.3 ± 1.9 mm and 23.8 ± 1.7 mm, respectively; P > .2). In contrast, we noted statistically significant differences between cases and controls in nasal floor canting (5.4° ± 4.6° and 1.8° ± 1.5°, respectively; P < .001) and height difference between the right and left nasal floors (1.8 ± 1.2 mm and 1.0 ± 0.7 mm, respectively; P = .002). CONCLUSIONS: Nasal floor canting of 3° or greater and a height difference between the right and left nasal floors of 1.5 mm or greater may contribute to the etiology of clinically relevant nasal obstruction. A piriform aperture width of 22 mm or less may be considered narrow. Future studies can determine when and how exactly to surgically address a clinically relevant narrow piriform aperture and nasal floor canting.

[Sexual Behavior and High-Risk HPV Infection in the Head and Neck]. / High-Risk-HPV-Infektionen im Kopf-Hals-Bereich ­ Welche Bedeutung hat das Sexualverhalten?

In the second half of the 20th century, the sexual revolution went hand in hand with changes in common sexual practices. At the turn of the millennium, an increase in the detection rate of HPV-positive oropharyngeal carcinomas (OPC) in the USA was observed for the first time. An increase in the OPC was also observed in Europe. It was shown that this increase was due to HPV-positive OPC. However, the detection rate of the HPV-positive OPC has national and regional differences. Within Europe, the highest detection rate is in Northern Europe (56,5 %), followed by Central Europe (37,6 %). An association between patients with OPC and ≥ 6 sexual partners (OR = 1,25) and ≥ 4 oral sex partners (OR = 2,25) has been described. An HPV infection is usually asymptomatic and eliminated by the immune system within a few months. The persistence of the virus is oncogene. Smoking favors virus persistence, which is why the combination of smoking and oral sex with ≥ 5 partners is a particular risk factor. It was also examined whether partners from patients with cervical cancer have an increased oropharyngeal HPV infection rate. There was no definite declaration on this, but further investigations are required. Oral condoms or dental dams are suitable for the prevention of an oral HPV infection. The studies regarding the effectiveness of HPV vaccination for the prevention of an OPC are poor. Authors described a significantly lower detection rate of oral HPV infection in vaccinated people than in non-vaccinated people (0,11 % vs. 1,61 %; p = 0,008).

Alarin in different human intestinal epithelial cell types.

Alarin (AL), a new member of the galanin family, has been localized in various CNS regions, mainly in rodents. Among other effects, it modulates food intake. Therefore, we analyzed the immunohistochemical distribution pattern of AL in human intestinal epithelia. Cryosections of 12 human bowel samples were immunohistochemically double-stained for AL and α-defensin 5 (αD; first set). Two further sets of sections were quadruple-stained either (second set) for AL, chromogranin (CG), synaptophysin (SY), and somatostatin (SO) or (third set) for AL, CG, Peptide Y (PY), and 5-hydroxytryptamine (5-HT). Slides were digitized and quantitative analysis of co-localization rates was undertaken. Small bowel: most of AL-positive cells (56%) were αD-positive Paneth cells located within the base of the crypts (first set). In the second set, about 27% of AL-labeled cells were co-reactive for SY and CG, likely representing entero-endocrine cells. In the third set, the largest subpopulation of AL-positive cells was not co-reactive for other markers applied (89%); most of them were likely Paneth cells. Large bowel: co-localization of AL with αD was not detected (first set). In the second set, AL was frequently co-localized with the other three markers applied (68%). In the third set, AL was frequently co-localized with 5-HT and CG (31%) as well as with PY and 5-HT (22%). Due to its presence in various enteroendocrine as well as Paneth cells, AL may be involved in different physiological and pathological processes.

Left frontal hub connectivity delays cognitive impairment in autosomal-dominant and sporadic Alzheimer's disease.

Patients with Alzheimer's disease vary in their ability to sustain cognitive abilities in the presence of brain pathology. A major open question is which brain mechanisms may support higher reserve capacity, i.e. relatively high cognitive performance at a given level of Alzheimer's pathology. Higher functional MRI-assessed functional connectivity of a hub in the left frontal cortex is a core candidate brain mechanism underlying reserve as it is associated with education (i.e. a protective factor often associated with higher reserve) and attenuated cognitive impairment in prodromal Alzheimer's disease. However, no study has yet assessed whether such hub connectivity of the left frontal cortex supports reserve throughout the evolution of pathological brain changes in Alzheimer's disease, including the presymptomatic stage when cognitive decline is subtle. To address this research gap, we obtained cross-sectional resting state functional MRI in 74 participants with autosomal dominant Alzheimer's disease, 55 controls from the Dominantly Inherited Alzheimer's Network and 75 amyloid-positive elderly participants, as well as 41 amyloid-negative cognitively normal elderly subjects from the German Center of Neurodegenerative Diseases multicentre study on biomarkers in sporadic Alzheimer's disease. For each participant, global left frontal cortex connectivity was computed as the average resting state functional connectivity between the left frontal cortex (seed) and each voxel in the grey matter. As a marker of disease stage, we applied estimated years from symptom onset in autosomal dominantly inherited Alzheimer's disease and cerebrospinal fluid tau levels in sporadic Alzheimer's disease cases. In both autosomal dominant and sporadic Alzheimer's disease patients, higher levels of left frontal cortex connectivity were correlated with greater education. For autosomal dominant Alzheimer's disease, a significant left frontal cortex connectivity × estimated years of onset interaction was found, indicating slower decline of memory and global cognition at higher levels of connectivity. Similarly, in sporadic amyloid-positive elderly subjects, the effect of tau on cognition was attenuated at higher levels of left frontal cortex connectivity. Polynomial regression analysis showed that the trajectory of cognitive decline was shifted towards a later stage of Alzheimer's disease in patients with higher levels of left frontal cortex connectivity. Together, our findings suggest that higher resilience against the development of cognitive impairment throughout the early stages of Alzheimer's disease is at least partially attributable to higher left frontal cortex-hub connectivity.

GAL3 receptor knockout mice exhibit an alcohol-preferring phenotype.

Galanin is a neuropeptide which mediates its effects via three G-protein coupled receptors (GAL1-3 ). Administration of a GAL3 antagonist reduces alcohol self-administration in animal models while allelic variation in the GAL3 gene has been associated with an increased risk of alcohol use disorders in diverse human populations. Based on the association of GAL3 with alcoholism, we sought to characterize drug-seeking behavior in GAL3 -deficient mice for the first time. In the two-bottle free choice paradigm, GAL3 -KO mice consistently showed a significantly increased preference for ethanol over water when compared to wildtype littermates. Furthermore, male GAL3 -KO mice displayed significantly increased responding for ethanol under operant conditions. These differences in alcohol seeking behavior in GAL3 -KO mice did not result from altered ethanol metabolism. In contrast to ethanol, GAL3 -KO mice exhibited similar preference for saccharin and sucrose over water, and a similar preference for a high fat diet over a low fat diet as wildtype littermates. No differences in cognitive and locomotor behaviors were observed in GAL3 -KO mice to account for increased alcohol seeking behavior. Overall, these findings suggest genetic ablation of GAL3 in mice increases alcohol consumption.

Lithium and Not Acetoacetate Influences the Growth of Cells Treated with Lithium Acetoacetate.

The ketogenic diet (KD), a high-fat/low-carbohydrate/adequate-protein diet, has been proposed as a treatment for a variety of diseases, including cancer. KD leads to generation of ketone bodies (KBs), predominantly acetoacetate (AcAc) and 3-hydroxy-butyrate, as a result of fatty acid oxidation. Several studies investigated the antiproliferative effects of lithium acetoacetate (LiAcAc) and sodium 3-hydroxybutyrate on cancer cells in vitro. However, a critical point missed in some studies using LiAcAc is that Li ions have pleiotropic effects on cell growth and cell signaling. Thus, we tested whether Li ions per se contribute to the antiproliferative effects of LiAcAc in vitro. Cell proliferation was analyzed on neuroblastoma, renal cell carcinoma, and human embryonic kidney cell lines. Cells were treated for 5 days with 2.5, 5, and 10 mM LiAcAc and with equimolar concentrations of lithium chloride (LiCl) or sodium chloride (NaCl). LiAcAc affected the growth of all cell lines, either negatively or positively. However, the effects of LiAcAc were always similar to those of LiCl. In contrast, NaCl showed no effects, indicating that the Li ion impacts cell proliferation. As Li ions have significant effects on cell growth, it is important for future studies to include sources of Li ions as a control.

Untargeted Metabolomics Reveals Molecular Effects of Ketogenic Diet on Healthy and Tumor Xenograft Mouse Models.

The application of ketogenic diet (KD) (high fat/low carbohydrate/adequate protein) as an auxiliary cancer therapy is a field of growing attention. KD provides sufficient energy supply for healthy cells, while possibly impairing energy production in highly glycolytic tumor cells. Moreover, KD regulates insulin and tumor related growth factors (like insulin growth factor-1, IGF-1). In order to provide molecular evidence for the proposed additional inhibition of tumor growth when combining chemotherapy with KD, we applied untargeted quantitative metabolome analysis on a spontaneous breast cancer xenograft mouse model, using MDA-MB-468 cells. Healthy mice and mice bearing breast cancer xenografts and receiving cyclophosphamide chemotherapy were compared after treatment with control diet and KD. Metabolomic profiling was performed on plasma samples, applying high-performance liquid chromatography coupled to tandem mass spectrometry. Statistical analysis revealed metabolic fingerprints comprising numerous significantly regulated features in the group of mice bearing breast cancer. This fingerprint disappeared after treatment with KD, resulting in recovery to the metabolic status observed in healthy mice receiving control diet. Moreover, amino acid metabolism as well as fatty acid transport were found to be affected by both the tumor and the applied KD. Our results provide clear evidence of a significant molecular effect of adjuvant KD in the context of tumor growth inhibition and suggest additional mechanisms of tumor suppression beyond the proposed constrain in energy supply of tumor cells.

Melanoma tumors exhibit a variable but distinct metabolic signature.

The Warburg theory of cancer postulates that an important driver of tumorigenesis is insufficient respiration due to mitochondrial defects, and concomitant enhancement of lactate production due to increased aerobic glycolysis. We analysed 48 melanoma samples by immunohistochemistry and found that 38% of melanomas are characterized by areas of isolated or combined deficiencies of complexes of the oxidative phosphorylation (OXPHOS) system, whereby the incidence of OXPHOS-deficient areas is associated with an increased Breslow index; 62% of melanomas showed high expression of all OXPHOS complexes. Expression of carbonic anhydrase IX was low, indicating that melanomas generally are well-oxygenated. Expression of HIF-1α and MCT4 was high, which might be a consequence of increased lactate dehydrogenase A levels in melanomas. Our data indicate that there are two types of melanomas: one that features a classic Warburg effect, whereas the other one, despite being glycolytic, maintains a high level of OXPHOS complexes.

Effects of galanin receptor 2 and receptor 3 knockout in mouse models of acute seizures.

There exists solid evidence that endogenous galanin and galanin agonists exert anticonvulsive actions mediated both by galanin 1 receptor (GAL1-R) and galanin 2 receptor (GAL2-R). We have now investigated whether depletion of the recently identified third galanin receptor, GAL3-R, and that of GAL2-R, alters the threshold to the systemically applied γ-aminobutyric acid (GABA) antagonist pentylenetetrazole (PTZ) or to intrahippocampally administered kainic acid (KA). In neither model, GAL3-KO mice differed in their latency to the first seizure, mean seizure duration, total number of seizures, or time spent in seizures compared to wild-type controls. In addition, consistent with previous data, the response to PTZ was not altered in GAL2-KO mice. In contrast, intrahippocampal KA resulted in a significantly increased number of seizures and time spent in seizures in GAL2-KO mice, although the latency to the first seizure and the duration of individual seizures was not altered. These results are consistent with the previous data showing that GAL2-R knockdown does not affect the number of perforant path stimulations required for initiating status epilepticus but significantly increases the seizure severity during the ongoing status. In conclusion, our data support a specific role of GAL2-R but not of GAL3-R in mediating the anticonvulsive actions of endogenous galanin.