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This study aimed to investigate the antimigraine potential of quercetin in migraine pain induced by nitroglycerin (NTG), 10 mg/kg, intraperitoneal injection in rats. Quercetin was administered orally for 1 week, and behavioral parameters associated with pain were assessed 30 min after NTG injection. At the end of the study, the rats were killed so that immunohistochemical examination of their brains could be performed. The time and frequency of rearing and sniffing in the category of exploratory behavior, walking in the category of locomotor behavior, and total time spent in the light chamber were reduced in the disease control group compared with the normal group during the assessment of behavioral parameters. Pathologic migraine criteria, such as increased levels of calcitonin gene-related peptide and increased release of c-fos cells, were more prominent in the caudal nucleus triceminalis of the NTG control group. In the treatment groups, behavioral and pathological measures were less severe after pretreatment with quercetin at doses of 250 and 500 mg/kg. Therefore, it was concluded that quercetin improved the pain behavior of migraine patients in the NTG-induced migraine rat model. Quercetin is thought to have antimigraine effects due to its antioxidant and anti-inflammatory potential. Quercetin may therefore be a novel agent that can treat or prevent migraine pain and associated avoidance behaviors.

Nonhuman primates have a highly diverse locomotor repertoire defined by an equally diverse hand use. Based on how primates use their hands during locomotion, we can distinguish between terrestrial and arboreal taxa. The 'arboreal' hand is likely adapted towards high wrist mobility and grasping, whereas the 'terrestrial' hand will show adaptations to loading. While the morphology of the forearm and hand bones have been studied extensively, functional adaptations in the forearm and hand musculature to locomotor behaviour have been documented only scarcely. In this paper, we investigate the forelimb musculature of the highly arboreal gibbons (including Hylobates lar,Hylobates pileatus,Nomascus leucogenys,Nomascus concolor and Symphalangus syndactylus) and compare this with the musculature of the semi-terrestrial rhesus macaques (Macaca mulatta). Anatomical data from previous dissections on knuckle-walking bonobos (Pan paniscus) and bipedal humans (Homo sapiens) are also included to further integrate the analyses in the scope of catarrhine hand adaptation. This study indicates that the overall configuration of the arm and hand musculature of these primates is very similar but there are some apparent differences in relative size which can be linked to differences in forelimb function and which might be related to their specific locomotor behaviour. In macaques, there is a large development of wrist deviators, wrist and digital flexors, and m. triceps brachii, as these muscles are important during the different phases of palmi- and digitigrade quadrupedal walking to stabilize the wrist and elbow. In addition, their m. flexor carpi ulnaris is the most important contributor to the total force-generating capacity of the wrist flexors and deviators, and is needed to counteract the adducting torque at the elbow joint during quadrupedal walking. Gibbons show a relatively high force-generating capacity in their forearm rotators, wrist and digital flexors, which are important muscles in brachiation to actively regulate forward movement of the body. The results also stress the importance of the digital flexors in bonobos, during climbing and clambering, and in humans, which is likely linked to our advanced manipulation skills. ispartof: JOURNAL OF ANATOMY vol:238 issue:2 pages:321-337 ispartof: location:England status: published

Zebrafish are increasingly being utilized as a model to investigate infectious diseases and to advance the understanding of pathogen–host interactions. Here, we take advantage of the zebrafish to recapitulate congenital ZIKV infection and, for the first time, demonstrate that it can be used to model infection and reinfection and monitor anti-viral and inflammatory immune responses, as well as brain growth and eye abnormalities during embryonic development. By injecting a Brazilian strain of ZIKV into the yolk sac of one-cell stage embryos, we confirmed that, after 72 h, ZIKV successfully infected larvae, and the physical condition of the virus-infected hosts included gross morphological changes in surviving embryos (84%), with a reduction in larval head size and retinal damage characterized by increased thickness of the lens and inner nuclear layer. Changes in locomotor activity and the inability to perceive visual stimuli are a result of changes in retinal morphology caused by ZIKV. Furthermore, we demonstrated the ability of ZIKV to replicate in zebrafish larvae and infect new healthy larvae, impairing their visual and neurological functions. These data reinforce the deleterious activity of ZIKV in the brain and visual structures and establish the zebrafish as a model to study the molecular mechanisms involved in the pathology of the virus.

Waterborne Benzo[a]pyrene (B[a]P) pollution is a global threat to aquatic organisms. The exposure to waterborne B[a]P can disrupt the normal locomotor behavior of zebrafish (Danio rerio), however, how it affect the locomotor behavior of adult zebrafish remains unclear. Herein, B[a]P at two concentrations (0.8 μg/L and 2.0 μg/L) were selected to investigate the molecular mechanisms of the affected locomotor behavior of zebrafish by B[a]P based on transcriptome profiling. Adverse effects of B[a]P exposure affecting locomotor behavior in zebrafish were studied by RNA sequencing, and the locomotion phenotype was acquired. The gene enrichment results showed that the differentially highly expressed genes (atp2a1, cdh2, aurka, fxyd1, clstn1, apoc1, mt-co1, tnnt3b, and fads2) of zebrafish are mainly enriched in adrenergic signaling in cardiomyocytes (dre04261) and locomotory behavior (GO:0007626). The movement trajectory plots showed an increase in the locomotor distance and velocity of zebrafish in the 0.8 μg/L group and the opposite in the 2.0 μg/L group. The results showed that B[a]P affects the variety of genes in zebrafish, including motor nerves, muscles, and energy supply, and ultimately leads to altered locomotor behavior.

Sulfometuron methyl (SM) is a widely used herbicide and thus leading to accumulation in the environment. The toxicity assessments of SM in model organisms are currently rare. In the present study, zebrafish were utilized for evaluating the detrimental effects of SM in aquatic vertebrates. Zebrafish embryos were exposed to 0, 10, 20, and 40 mg/L SM from 5.5 to 72 h post-fertilization (hpf), respectively. Consequently, SM exposure resulted in increasing the mortality rate and reducing hatching rate in larval zebrafish at 10, 20, and 40 mg/L SM-treated groups. The reduced numbers of immune cells (neutrophils and macrophages) were observed after SM exposure by a dose-dependent manner. The inflammatory responses (TLR4, MYD88, IL-1β, IL-6, IL-8, IFN-γ, IL-10, and TGF-β) were measured to estimate immune responses. Anti-inflammatory factors (IL-10 and TGF-β) were down-regulated in all the treated groups and significantly altered at 40 mg/L exposure group. Additionally, behavioral tests suggested that SM treatment significantly increased the total distance, average speed, and maximum acceleration of larval zebrafish during light-dark transition and subsequently enzymology test displayed the same trend to locomotor behaviors. The content significantly increased in oxidative stress, as reflected in ROS level in all the treated groups. The numbers of cell apoptosis were significantly increased at 20, and 40 mg/L and the highest concentration group induced the substantial increment (P

Due to lack of low-cost and convenient measurement procedures, uncontrolled changes in spontaneous physical activity (SPA) level often are insufficiently considered as a confounding factor in rodent studies. Nonetheless, alterations in SPA can significantly impact on a wide range of physiological measurements. Therefore, we developed an accurate, low-cost video tracking procedure to allow routine assessment of SPA in the home cage of experimental animals (i.e., mice) and in the absence of any distress that might cause alterations in SPA. SPA parameters acquired (movement distance, movement time, and movement speed) with the novel tracking system were identical to those simultaneously obtained with a high-end and well-validated movement-tracking device (mean error = 0.15 ± 0.07%, r = 0.99, P < 0.001). To further validate the setup, we also demonstrated caffeine-induced stimulation of SPA (195% more activity compared with vehicle, P < 0.01), we adequately reproduced typical SPA fluctuations inherent to day/night cycles (146 and 702% more active during nocturnal compared with diurnal cycle for Balb/c and C57BL/6J mice, respectively, P < 0.001), and we confirmed previously documented SPA differences between animal strains (24% less activity in C57BL/6J mice compared with Balb/c mice, P < 0.05). Taken together, we provide data to prove that this novel low-cost methodology can be conveniently used in any mouse experiment where uncontrolled changes in SPA due to experimental interventions might confound data interpretation. By analogy, the system can be used to document a beneficial impact of therapeutic interventions on SPA in any disease mouse model. NEW & NOTEWORTHY We developed a low-cost procedure to routinely measure SPA in mice. The procedure maintains normal SPA because the animals continue to stay in their home cage in the absence of any external manipulation by the investigators and under habitual dark/light ambient conditions. This novel methodology can be conveniently used in any mouse experiment to quantify experimentally induced alterations in SPA or to assess natural variations in SPA that might confound data interpretation. ispartof: J Appl Physiol (1985) vol:125 issue:2 pages:263-270 ispartof: location:United States status: published

How global warming changes the toxicity of contaminants is a research priority at the intersection of global change biology and ecotoxicology. While many pesticides are more toxic at higher temperatures this is not always detected. We studied whether deviations from this general pattern can be explained by concentration-dependent interaction effects and by testing the interaction against the inappropriate null model. We exposed larvae of the mosquito Culex pipiens to three concentrations of the pesticide chlorpyrifos (absence, low and high) in the absence and presence of 4 °C warming. Both the low and high chlorpyrifos concentration were lethal and generated negative sublethal effects: activity of acetylcholinesterase (AChE) and total fat content decreased, and oxidative damage to lipids increased, yet growth rate increased. Warming was slightly lethal, yet had positive sublethal effects: growth rate, total fat content and metabolic rate increased, and oxidative damage decreased. For four out of seven response variables the independent action model identified the expected synergistic interaction between chlorpyrifos and warming. Notably, for three variables (survival, AChE and fat content) this was strongly dependent on the chlorpyrifos concentration, and for two of these (AChE and fat content) not associated with a significant interaction in the general(ized) linear models. For survival and fat content, warming only potentiated chlorpyrifos (CPF) toxicity at the low CPF concentration, while the opposite was true for AChE. Our results highlight that taking into account concentration-dependence and appropriate null model testing is crucial to improve our understanding of the toxicity of contaminants in a warming world. ispartof: AQUATIC TOXICOLOGY vol:211 pages:38-45 ispartof: location:Netherlands status: published

Background Galectins are a large family of proteins evolved to recognize specific carbohydrate moieties. Given the importance of pattern recognition processes for multiple biological tasks, including CNS development and immune recognition, we examined the home cage behavioral phenotype of mice lacking galectin-3 (Lgals3) function. Using a sophisticated monitoring apparatus capable of examining feeding, drinking, and movement at millisecond temporal and 0.5 cm spatial resolutions, we observed daily behavioral patterns from 10 wildtype male C57BL/6J and 10 Lgals3 constitutive knockout (Lgals3−/−; both cohorts aged 2–3 months) mice over 17 consecutive days. We performed a second behavioral assessment of this cohort at age 6–7 months. Results At both ages, Lgals3−/− mice demonstrated less movement compared to wildtype controls. Both forward locomotion and movement-in-place behaviors were decreased in Lgals3−/− mice, due to decreased bout numbers, initiation rates, and durations. We additionally noted perturbation of behavioral circadian rhythms in Lgals3−/− mice, with mice at both ages demonstrating greater variability in day-to-day performance of feeding, drinking, and movement (as assessed by Lomb-Scargle analysis) compared to wildtype. Conclusion Carbohydrate recognition tasks performed by Lgals3 may be required for appropriate development of CNS structures involved in the generation and control of locomotor behavior. Electronic supplementary material The online version of this article (10.1186/s12868-018-0428-x) contains supplementary material, which is available to authorized users.

In the brain, NO is a very important molecule in the regulation of cerebral and extra cerebral cranial blood flow and arterial diameters. It is also importantly involved in many neuronal functions and innumerable roles of NO in many brain related disorders including epilepsy, schizophrenia, drug addiction, anxiety, major depression, have been postulated. The present study aimed to explore the neuronal role exerted by the metal-nonoate compound Ni(PipNONO)Cl, a novel NO donor whose vascular protective effects have been recently demonstrated. Ni(PipNONO)Cl showed antidepressant-like properties in the tail suspension test and antiamnesic activity in the passive avoidance test in the absence of any hypernociceptive response to a mechanical stimulus. These effects were related to the NO-releasing properties of the compound within the central nervous system as demonstrated by the increase of iNOS levels in the brain, spinal cord and dura mater. The modulation of neuronal functions appeared after acute and repeated treatment, showing the lack of any tolerance to neuronal effects. At the dose used (10 mg/kg i.p.), Ni(PipNONO)Cl did not induce any visible sign of toxicity and experiments were performed in the absence of locomotor impairments. In addition to the NO-related neuronal activities of Ni(PipNONO)Cl, the decomposition control compound Ni(Pip)Cl2 showed anxiogenic-like and procognitive effects. The present findings showed neuronal modulatory activity of Ni(PipNONO)Cl through a NO-mediated mechanism. The activities of the decomposition compound Ni(Pip)Cl2 attributed to Ni(PipNONO)Cl the capability to modulate additional neuronal functions independently from NO releasing properties extending and improving the therapeutic perspectives of the NO donor.

Glucocorticoids (GCs) are known to alter neuronal plasticity, impair learning and memory and play important roles in the generation and progression of Alzheimer's disease. There are no effective drug options for preventing neuronal injury induced by chronic GC exposure. Ginsenoside Rg1 (Rg1) is a steroidal saponin found in ginseng. The present study investigated the neuroprotective effect of Rg1 on neuroinflammation damage induced by chronic dexamethasone (5 mg/kg for 28 days) exposure in male mice. Our results showed that Rg1 (2 and 4 mg/kg) treatment increased spontaneous motor activity and exploratory behavior in an open field test, and increased the number of entries into the new object zone in a novel object recognition test. Moreover, Rg1 (2 and 4 mg/kg) treatment significantly alleviated neuronal degeneration and increased MAP2 expression in the frontal cortex and hippocampus. Additionally, inhibition of NLRP‑1 inflammasomes was also involved in the mechanisms underlying the effect of Rg1 on GC‑induced neuronal injury. We found that Rg1 (2 and 4 mg/kg) treatment increased the expression of glucocorticosteroid receptor and decreased the expression of NLRP‑1, ASC, caspase‑1, caspase‑5, IL‑1β and IL‑18 in the hippocampus in male mice. The present study indicates that Rg1 may have protective effects on neuroinflammation and neuronal injury induced by chronic GC exposure.

In the visual systems of insects, different types of photoreceptors contribute to specialized visual channels that mediate distinct functions and behaviors. Large compound eyes of Periplaneta americana contain photoreceptors of two spectral classes, broadband green-sensitive photoreceptors and narrow-band UV-sensitive photoreceptors. Here, we investigated how visual stimulation by UV and green light affects locomotor, resting, and grooming behaviors in P. americana under conditions when light avoidance is not possible. We show that green but not UV light stimulates locomotor activity, inducing paradoxical positive masking. Duration of resting and grooming decreased with increasing light intensity, consistent with development of behavioral stress in response to visual overstimulation. A reaction of full immobility is described under UV light and at higher intensities of green light, with relative periods of immobility and grooming strongly negatively correlated. Low-intensity UV was more effective than low-intensity green light in suppressing grooming and inducing immobility. Our results suggest that locomotor activity in P. americana is mainly regulated by green-sensitive photoreceptors, and that dim UV light can trigger behavioral immobility, whereas both wavelengths induce stress-like reactions at high intensities. Considering the intrinsic UV sensitivity of green-sensitive photoreceptors, the contrasting behavioral responses indicate antagonistic interactions between UV and green visual channels.

The cerebellum is a structure of the central nervous system involved in balance, motor coordination, and voluntary movements. The elementary circuit implicated in the control of locomotion involves Purkinje cells, which receive excitatory inputs from parallel and climbing fibers, and are regulated by cerebellar interneurons. In mice as in human, the cerebellar cortex completes its development mainly after birth with the migration, differentiation, and synaptogenesis of granule cells. These cellular events are under the control of numerous extracellular matrix molecules including pleiotrophin (PTN). This cytokine has been shown to regulate the morphogenesis of Purkinje cells ex vivo and in vivo via its receptor PTPζ. Since Purkinje cells are the unique output of the cerebellar cortex, we explored the consequences of their PTN-induced atrophy on the function of the cerebellar neuronal circuit in mice. Behavioral experiments revealed that, despite a normal overall development, PTN-treated mice present a delay in the maturation of their flexion reflex. Moreover, patch clamp recording of Purkinje cells revealed a significant increase in the frequency of spontaneous excitatory postsynaptic currents in PTN-treated mice, associated with a decrease of climbing fiber innervations and an abnormal perisomatic localization of the parallel fiber contacts. At adulthood, PTN-treated mice exhibit coordination impairment on the rotarod test associated with an alteration of the synchronization gait. Altogether these histological, electrophysiological, and behavior data reveal that an early ECM disruption of PTN composition induces short- and long-term defaults in the establishment of proper functional cerebellar circuit.

Context. Coriandrum sativum L. (Apiaceae) (coriander) is an herb grown throughout the world as a culinary, medicinal or essential crop. In traditional medicine, it is used for the relief of anxiety and insomnia. Systemic hydro-alcoholic and aqueous extract from aerial parts and seeds had anxiolytic and sedative action in rodents, but little is known about its central effect in chicks. Objective To study the effects of intracerebroventricular administration of essential oil from coriander seeds and its major component linalool on locomotor activity and emotionality of neonatal chicks. Materials and methods. The chemical composition of coriander essential oil was determined by a gas-chromatographic analysis (> 80% linalool). Behavioural effects of central administration of coriander oil and linalool (both at doses of 0.86, 8.6 and 86 μg/chick) versus saline and a sedative diazepam dose (17.5 μg/chick, standard drug) in an open field test for 10 min were observed. Results. Doses of 8.6 and 86 μg from coriander oil and linalool significantly decreased (p < 0.05) squares crossed number, attempted escapes, defecation number and distress calls, and significantly increased (p < 0.05) the sleeping posture on an open field compared with saline and were similar to the diazepam group. Discussion and conclusion. The results indicate that intracerebroventricular injection of essential oil from Coriandrum sativum seeds induced a sedative effect at 8.6 and 86 μg doses. This effect may be due to monoterpene linalool, which also induced a similar sedative effect, and, therefore, could be considered as a potential therapeutic agent similar to diazepam. Fil: Gastón, María Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; Argentina Fil: Cid, Mariana Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; Argentina Fil: Vázquez, Ana María. Universidad Catolica de Córdoba. Facultad de Ciencias Químicas; Argentina Fil: Decarlini, Maria Florencia. Universidad Catolica de Córdoba. Facultad de Ciencias Químicas; Argentina Fil: Demmel, Gabriela Ines. Universidad Catolica de Córdoba. Facultad de Ciencias Químicas; Argentina Fil: Rossi, Laura Isabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; Argentina Fil: Aimar, Mario Leandro. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales; Argentina Fil: Salvatierra, Nancy Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; Argentina

In this study, we evaluated the acute (24, 48, 72, and 96 h) and chronic (21 days) adverse effects induced by low doses (0.1, 0.5, 1, and 1.5 mg/L) of zinc chloride (ZnCl2) exposure in adult zebrafish by using behavioral endpoints like three-dimensional (3D) locomotion, passive avoidance, aggression, circadian rhythm, and predator avoidance tests. Also, brain tissues were dissected and subjected to analysis of multiple parameters related to oxidative stress, antioxidant responses, superoxide dismutase (SOD), neurotoxicity, and neurotransmitters. The results showed that ZnCl2-exposed fishes displayed decreased locomotor behavior and impaired short-term memory, which caused an Alzheimer&rsquo, s Disease (AD)-like syndrome. In addition, low concentrations of ZnCl2 induced amyloid beta (amyloid &beta, ) and phosphorylated Tau (p-Tau) protein levels in brains. In addition, significant induction in oxidative stress indices (reactive oxygen species (ROS) and malondialdehyde (MDA)), reduction in antioxidant defense system (glutathione (GSH), GSH peroxidase (GSH-Px) and SOD) and changes in neurotransmitters were observed at low concentrations of ZnCl2. Neurotoxic effects of ZnCl2 were observed with significant inhibition of acetylcholine (ACh) activity when the exposure dose was higher than 1 ppm. Furthermore, we found that zinc, metallothionein (MT), and cortisol levels in brain were elevated compared to the control group. A significantly negative correlation was observed between memory and acetylcholinesterase (AChE) activity. In summary, these findings revealed that exposure to ZnCl2 affected the behavior profile of zebrafish, and induced neurotoxicity which may be associated with damaged brain areas related to memory. Moreover, our ZnCl2-induced zebrafish model may have potential for AD-associated research in the future.

In common voles (Microtus arvalis), natural variation in locomotor behavior can be exploited to study the mechanism of pacemaker control over circadian timing of behavior. Here we studied daily patterns in numbers of neuropeptide immunoreactive suprachiasmatic nucleus neurons in rhythmic, weakly rhythmic, and non-rhythmic voles. Circadian rhythmic voles showed circadian variation in numbers of vasoactive intestinal polypeptide and vasopressin immunoreactive suprachiasmatic nucleus neurons with a peak at zeitgeber time 0. In contrast, voles with weak or no circadian rhythmicity exhibited similar fluctuations for vasoactive intestinal polypeptide, but a continuous, non-rhythmic high profile for vasopressin. Vole suprachiasmatic nucleus neurons do not produce somatostatin or substance P. We conclude that the vasopressin system in the common vole suprachiasmatic nucleus acts as a principal correlate with expression of circadian behavior, in contrast to vasoactive intestinal polypeptide, somatostatin, and substance P. We also conclude that high levels of vasopressin immunoreactivity in the non-rhythmic vole suprachiasmatic nucleus is in line with previously demonstrated hampered release, probably resulting in vasopressin accumulation in the suprachiasmatic nucleus. Vasopressin could be a candidate in mediating output of the vole circadian clock, leading to circadian expression of locomotor behavior. (C) 2007 Elsevier Ltd. All rights reserved.

miR-29 is expressed strongly in the brain and alterations in expression have been linked to several neurological disorders. To further explore the function of this miRNA in the brain, we generated miR-29a/b-1 knockout animals. Knockout mice develop a progressive disorder characterized by locomotor impairment and ataxia. The different members of the miR-29 family are strongly expressed in neurons of the olfactory bulb, the hippocampus and in the Purkinje cells of the cerebellum. Morphological analysis showed that Purkinje cells are smaller and display less dendritic arborisation compared to their wildtype littermates. In addition, a decreased number of parallel fibers form synapses on the Purkinje cells. We identified several mRNAs significantly up-regulated in the absence of the miR-29a/b-1 cluster. At the protein level, however, the voltage-gated potassium channel Kcnc3 (Kv3.3) was significantly up-regulated in the cerebella of the miR-29a/b knockout mice. Dysregulation of KCNO expression may contribute to the ataxic phenotype. (C) 2015 Elsevier Inc All rights reserved.

Vertebrate Hox genes regulate many aspects of embryonic body plan development and patterning. In particular, Hox genes have been shown to regulate regional patterning of the axial and appendicular skeleton and of the central nervous system. We have identified patterning defects resulting from the targeted mutation of Hoxc10, a member of the Hox10 paralogous family. Hoxc10 mutant mice have skeletal transformations in thoracic, lumbar, and sacral vertebrae and in the pelvis, along with alterations in the bones and ligaments of the hindlimbs. These results suggest that Hoxc10, along with other members of the Hox10 paralogous gene family, regulates vertebral identity at the transition from thoracic to lumbar and lumbar to sacral regions. Our results also suggest a general role for Hoxc10 in regulating chondrogenesis and osteogenesis in the hindlimb, along with a specific role in shaping femoral architecture. In addition, mutant mice have a reduction in lumbar motor neurons and a change in locomotor behavior. These results suggest a role for Hoxc10 in generating or maintaining the normal complement of lumbar motor neurons.

PMCID: PMC2574913; NIHMSID: NIHMS56479.-- et al., Many nervous system pathologies are associated with increased levels of apolipoprotein D (ApoD), a lipocalin also expressed during normal development and aging. An ApoD homologous gene in Drosophila, Glial Lazarillo, regulates resistance to stress, and neurodegeneration in the aging brain. Here we study for the first time the protective potential of ApoD in a vertebrate model organism. Loss of mouse ApoD function increases the sensitivity to oxidative stress and the levels of brain lipid peroxidation, and impairs locomotor and learning abilities. Human ApoD overexpression in the mouse brain produces opposite effects, increasing survival and preventing the raise of brain lipid peroxides after oxidant treatment. These observations, together with its transcriptional up-regulation in the brain upon oxidative insult, identify ApoD as an acute response protein with a protective and therefore beneficial function mediated by the control of peroxidated lipids., This work was supported by start-up grants to D.S. and M.D.G. from the ‘Ramon y Cajal Program’ (MEC-Spain and FEDER-FSE); the SGFRH Foundation; NIH grant 2/R01/ NS25387-10A1 to M.J.B.; CIHR grant MOP-15677 to E.R.; FRSQ and CRSNG studentships to S.d.C.; STINT fellowship KU2003-4308 to M.A.; DGICyT grant BFU2004-06394 and JCyL grant VA011C05 to C.G.; and MEC grant BFU2005-00522 and JCyL grant VA049A05 to M.D.G and D.S.

Humulus lupulus (hops) is traditionally used as a tranquilizing herbal remedy. Here, we investigated the in vivo and in vitro effect of hop beta-acids on central nervous system function. Oral administration of beta-acids (5-10mg/kg) in rats produced an increased exploratory activity in the open field, a reduction in the pentobarbital hypnotic activity and a worsening of picrotoxin-induced seizures. When dosed at 10mg/kg, beta-acids increased, in the elevated plus maze, open arm entries reducing in parallel those in closed arms. In the forced swimming test, we observed a reduction in the immobility time that could suggest an antidepressant-like activity. Electrophysiological studies performed on cerebellar granule cells in culture showed that the beta-acids fraction decreased GABA-evoked current in a dose-dependent way. The effect was not inhibited by the benzodiazepine antagonist Ro 15-1788. Benzodiazepine receptors involvement was also excluded by [(3)H]-Ro 15-1788 binding assay. In conclusion, the behavioral effects of beta-acids fraction could be explained by a reduction in the GABAergic activity although we cannot rule out the involvement of other neurotransmitter systems.

The purpose of the present study was to investigate the effects of Humulus lupulus CO2 extract and its fraction containing alpha-acids on the central nervous system of rats. Both tested substances were able to prolong pentobarbital sleeping time, without affecting the latency to the loss of the righting reflex. This effect was dose-dependent, starting from a minimal dose of 10 mg/kg. Neither the extract nor its alpha-acid fraction affected the locomotor activity in the open field test or exerted an anxiolytic effect in rats submitted to the elevated plus-maze test. Interestingly both compounds reduced the immobility time during the behavioral despair test when administered three times (24, 5 and 1 h) before the test. In conclusion this report shows that Humulus lupulus CO2 extract exerts: (a) a pentobarbital sleep-enhancing property without influencing the motor behavior of rats; (b) an antidepressant activity. The same effects were elicited by the administration of the Humulus lupulus fraction containing alpha-acids, which can be considered as the major responsible for the enhanced pentobarbital effect and for the antidepressant property.

The temporal properties of a variety of behavioral traits obey power law distributions, a property often referred to as fractal. We recently showed that the temporal pattern of locomotor activity of the fruitfly Drosophila melanogaster follows this distribution. Although an increasing number of such fractal patterns are being discovered, the brain areas and neuronal networks responsible remain unknown. In this study, we show that specifically blocking synapses established by neurons of the Drosophila ellipsoid-body, a substructure of the central complex in the brain, leads to a loss of the fractal properties in the temporal pattern. We conclude that the temporal fractal pattern of locomotor activity is regulated in the ellipsoid-body.

Clinical trials have extensively reported the ability of Hypericum perforatum extracts to exert a significant antidepressant activity. Hypericin, the main constituent of H. perforatum extract, is no more regarded as the active principle of the antidepressant activity of the drug. Hence, the question of which constituents are involved in the basic activity of the total extract, is still waiting for an answer. In the present study we focused our attention on the potential anxiolytic activity of H. perforatum total extract, and of some pure components such as protohypericin and a fraction containing hypericin and pseudohypericin. Herein we report that the total extract of H. perforatum increases the locomotor activity in the open field and exerts anxiolytic activity in the light-dark test, whereas the single components did not show any effect. Interestingly, the anxiolytic activity of the total extract was blocked by pretreatment of rats with the benzodiazepine antagonist Flumazenil, hence suggesting an implication of benzodiazepine receptor activation in the anxiolytic effect of H. perforatum extract. Electrophysiological studies, performed to gain more information on the mechanism of action, showed that hypericin reduced the GABA-activated chloride currents, while pseudohypericin did an opposite effect. Furthermore, both hypericin and pseudohypericin inhibited the activation of NMDA receptors.