PLoS Genet

The retinoid X receptors (RXRs) are ligand-activated transcription factors which heterodimerize with a number of nuclear hormone receptors, thereby controlling a variety of (patho)-physiological processes. Although synthetic RXR ligands are developed for the treatment of various diseases, endogenous ligand(s) for these receptors have not been conclusively identified. We show here that mice lacking cellular retinol binding protein (Rbp1-/-) display memory deficits reflecting compromised RXR signaling. Using HPLC-MS and chemical synthesis we identified in Rbp1-/- mice reduced levels of 9-cis-13,14-dihydroretinoic acid (9CDHRA), which acts as an RXR ligand since it binds and transactivates RXR in various assays. 9CDHRA rescues the Rbp1-/- phenotype similarly to a synthetic RXR ligand and displays similar transcriptional activity in cultured human dendritic cells. High endogenous levels of 9CDHRA in mice indicate physiological relevance of these data and that 9CDHRA acts as an endogenous RXR ligand

Food for mood: relevance of nutritional omega-3 fatty acids for depression and anxiety

The central nervous system (CNS) has the highest concentration of lipids in the organism after adipose tissue. Among these lipids, the brain is particularly enriched with polyunsaturated fatty acids (PUFAs) represented by the omega-6 (omega 6) and omega-3 (omega 3) series. These PUFAs include arachidonic acid (AA) and docosahexaenoic acid (DHA), respectively. PUFAs have received substantial attention as being relevant to many brain diseases, including anxiety and depression. This review addresses an important question in the area of nutritional neuroscience regarding the importance of omega 3 PUFAs in the prevention and/or treatment of neuropsychiatric diseases, mainly depression and anxiety. In particular, it focuses on clinical and experimental data linking dietary intake of omega 3 PUFAs and depression or anxiety. In particular, we will discuss recent experimental data highlighting how omega 3 PUFAs can modulate neurobiological processes involved in the pathophysiology of anxiety and depression. Potential mechanisms involved in the neuroprotective and corrective activity of omega 3 PUFAs in the brain are discussed, in particular the sensing activity of free fatty acid receptors and the activity of the PUFAs-derived endocannabinoid system and the hypothalamic-pituitary-adrenal axis

Le rôle des rétinoïdes dans le contrôle des fonctions cognitives chez la souris adulte

Nous avons étudié le rôle des rétinoïdes dans les processus cognitifs. Nous avons fourni la preuve que la mutation du récepteur RXRg générait des déficits de la mémoire de travail (MT). Nous avons suggéré que les fonctions diminuées de l hippocampe étaient à la base des déficits de MT chez les souris RXRg-/-. Nous avons aussi démontré que l ADH pouvait être un ligand endogène du RXRg. Nous avons révélé un dimorphisme sexuel dans les fonctions cognitives chez les souris RXRg-/-. Les déficits de MT étaient présents chez les femelles mutantes après ovariectomie et ce défaut a été renversé par les œstrogènes. Nous avons confirmé les déficits moteurs chez les souris RARb-/-, et avons démontré que la transmission dopaminergique diminuée est responsable de cette incapacité. Nous avons aussi démontré que la mutation RARb causait les déficits dans le processus de la barrière sensorimotrice , à la base duquel se trouve le dysfonction du système sérotonergique.We studied role of retinoids in modulation of cognitive processes in mice. We provided the first evidence that null mutation of RXRg generates working memory (WM) deficits and that upstream stages of information processing are not at the origin of such abnormalities. We suggested that decreased hippocampal functions underlie WM deficits in RXRg mutant mice. We also showed that DHA may act as RXRg endogenous ligand. We reported sexual dimorphism in cognitive functions of RXRg mutant mice. WM deficits were present in mutant females only after ovariectomy and such defect was reversed by oestrogen treatment. We confirmed motor deficits in RARb mutant mice and showed that decreased dopaminergic transmission in nigrostriatal pathway might be responsible for such disability. We also showed that null mutation of RARb causes deficits in sensorimotor gating processes, which might be underlied by serotonergic system dysfunction.STRASBOURG-Sc. et Techniques (674822102) / SudocSudocFranceF

Estrous cycle effects on behavior of C57BL/6J and BALB/cByJ female mice: implications for phenotyping strategies.

Systematic behavioral phenotyping of genetically modified mice is a powerful method with which to identify the molecular factors implicated in control of animal behavior, with potential relevance for research into neuropsychiatric disorders. A number of such disorders display sex differences, yet the use of female mice in phenotyping strategies has been a rare practice because of the potential variability related to the estrous cycle. We have now investigated the behavioral effects of the estrous cycle in a battery of behavioral tests in C57BL/6J and BALB/cByJ inbred strains of mice. Whereas the performance of BALB/cByJ female mice varied significantly depending on the phase of the estrous cycle in the open field, tail flick and tail suspension tests, the behavior of C57BL/6J females, with the exception of the tail suspension performance, remained stable across all four phases of the estrous cycle in all of the tests including open field, rotarod, startle reflex and pre-pulse inhibition, tail flick and hot plate. We also found that irrespective of the estrous cycle, the behavior of C57BL/6J females was different from that of BALB/cByJ groups in all of the behavioral paradigms. Such strain differences were previously reported in male comparisons, suggesting that the same inter-group differences can be revealed by studying female or male mice. In addition, strain differences were evident even for behaviors that were susceptible to estrous cycle modulations, although their detection might necessitate the constitution of large experimental groups

Retinoid X Receptor Gamma Control of Affective Behaviors Involves Dopaminergic Signaling in Mice

International audienc

Self-propelled inspection vehicle on omni wheels

In the article design of a self-propelled vehicle for inspecting ventilation ducts and ceiling structures in buildings equipped with omni wheels was presented. Such vehicles are used in places that are hard to reach for people. The vehicle was designed using the vehicle control system – ARDUINO. For this system dedicated program was written, which is used to operate it. The vehicle is remotely controlled by radio waves. Its range is about 100 meters and the power supply is a 12 V battery. The vehicle operator has joysticks (controllers) modelled on those used in game controllers that are used for precise vehicle control. The vehicle is equipped with cameras that allow to view the image in real time. The omni wheels have also been tested for strength by the finite element method (FEM). Carried out FEM analysis as part of the work allowed to determine the strength of omni wheels on the acting forces during vehicle movement

Self-propelled inspection vehicle on omni wheels

In the article design of a self-propelled vehicle for inspecting ventilation ducts and ceiling structures in buildings equipped with omni wheels was presented. Such vehicles are used in places that are hard to reach for people. The vehicle was designed using the vehicle control system – ARDUINO. For this system dedicated program was written, which is used to operate it. The vehicle is remotely controlled by radio waves. Its range is about 100 meters and the power supply is a 12 V battery. The vehicle operator has joysticks (controllers) modelled on those used in game controllers that are used for precise vehicle control. The vehicle is equipped with cameras that allow to view the image in real time. The omni wheels have also been tested for strength by the finite element method (FEM). Carried out FEM analysis as part of the work allowed to determine the strength of omni wheels on the acting forces during vehicle movement

Working memory deficits in retinoid X receptor γ-deficient mice

Retinoid signaling has been recently shown to be required for mnemonic functions in rodents. To dissect the behavioral and molecular mechanisms involved in this requirement, we have analyzed the spatial and recognition working memory in mice carrying null mutations of retinoid receptors RARβ and RXRγ. Double mutants appeared deficient in spatial working memory as tested in spontaneous alternation in the Y-maze and delayed nonmatch to place (DNMTP) test in the T-maze. These mutant mice did acquire, however, spatial place reference or right/left discrimination tasks in the T-maze set-up, indicating that basic sensorimotor functions, spatial orientation, and motivational factors are unlikely to account for deficits in working memory-sensitive tasks. Double-mutant mice were also deficient in novel object recognition at intermediate, but not short delays. RXRγ appeared to be the functionally predominant receptor in modulation of the working memory, as RXRγ, but not RARβ single null mutant mice exhibited deficits similar to those observed in the double mutants. The mechanism of this modulation is potentially related to functions of RXRγ in frontal and perirhinal cortex, structures in which we detected RXRγ expression and which are functionally implicated in working memory processes

Retinoid hyposignaling contributes to aging-related decline in hippocampal function in short-term/working memory organization and long-term declarative memory encoding in mice.

An increasing body of evidence indicates that the vitamin A metabolite retinoic acid (RA) plays a role in adult brain plasticity by activating gene transcription through nuclear receptors. Our previous studies in mice have shown that a moderate downregulation of retinoid-mediated transcription contributed to aging-related deficits in hippocampal long-term potentiation and long-term declarative memory (LTDM). Here, knock-out, pharmacological, and nutritional approaches were used in a series of radial-arm maze experiments with mice to further assess the hypothesis that retinoid-mediated nuclear events are causally involved in preferential degradation of hippocampal function in aging. Molecular and behavioral findings confirmed our hypothesis. First, a lifelong vitamin A supplementation, like short-term RA administration, was shown to counteract the aging-related hippocampal (but not striatal) hypoexpression of a plasticity-related retinoid target-gene, GAP43 (reverse transcription-PCR analyses, experiment 1), as well as short-term/working memory (STWM) deterioration seen particularly in organization demanding trials (STWM task, experiment 2). Second, using a two-stage paradigm of LTDM, we demonstrated that the vitamin A supplementation normalized memory encoding-induced recruitment of (hippocampo-prefrontal) declarative memory circuits, without affecting (striatal) procedural memory system activity in aged mice (Fos neuroimaging, experiment 3A) and alleviated their LTDM impairment (experiment 3B). Finally, we showed that (knock-out, experiment 4) RA receptor beta and retinoid X receptor gamma, known to be involved in STWM (Wietrzych et al., 2005), are also required for LTDM. Hence, aging-related retinoid signaling hypoexpression disrupts hippocampal cellular properties critically required for STWM organization and LTDM formation, and nutritional vitamin A supplementation represents a preventive strategy. These findings are discussed within current neurobiological perspectives questioning the historical consensus on STWM and LTDM system partition