The atypical 'hippocampal' glutamate receptor coupled to phospholipase D that controls stretch-sensitivity in primary mechanosensory nerve endings is homomeric purely metabotropic GluK2

ACKNOWLEDGEMENTS We would like to thank: Prof. Christophe Mulle, University of Bordeaux, France for the generous donation of the GluK2-Neo mice; Prof. Roberto Pellicciari and Prof. Maura Marinozzi, University of Perugia, Italy for the generous gift of PCCG-13; the Microscopy and Histology core facility at the Institute of Medical Sciences, University of Aberdeen for their support and assistance in some of the imaging in this work. We would also like to thank Prof. Gernot Riedel, University of Aberdeen UK and Prof. David Jane, University of Bristol UK for helpful comments during the work and discussion about drafts of this manuscript.Peer reviewedPublisher PD

Prenatal Stress Inhibits Hippocampal Neurogenesis but Spares Olfactory Bulb Neurogenesis

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Adult-born neurons are necessary for extended contextual discrimination

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Bulbar and hippocampal neurogenesis in control (CC), water restricted (CCr) and olfactory trained (P) control (NS) and prenatally-stressed (PS) mice.

<p>Bulbar and hippocampal neurogenesis in control (CC), water restricted (CCr) and olfactory trained (P) control (NS) and prenatally-stressed (PS) mice.</p

Prenatal stress has no impact on olfactory performances.

<p>(A) Scheme of the experiment. (B) Behavioral performances in a short-term memory task, n = 4 per group. (C) Behavioral performances in the olfactory discrimination learning task. (D) Number of trials to reach the criteria (2 consecutive blocks >85% successful trials) in the olfactory discrimination learning, n = 13 per group.</p

Prenatal stress does not disturb adult bulbar neurogenesis.

<p>(A) Illustration of Ki67-IR cells in the SVZ. (B) Sagittal view of the olfactory bulb. (C) High magnification of the granule cell layer of the olfactory bulb with 5-week-old CldU-IR cells. (D) Number of Ki67-IR cells in the dorsolateral corner of the SVZ, n = 9–12 per group. (E) Volume of the granule cell layer of the OB, n = 10–14 per group. (F) Number of 5-week-old CldU-IR cells in the GCL, n = 10–14 per group. (G) Illustration of CldU-NeuN-IR cells (white arrow) and of CldU-S100-IR cells (white star). (H) Percentage of CldU-NeuN-IR cells in the GCL, n = 5 per group. (I) Percentage of CldU-S100-IR cells in the GCL, n = 5 per group. Scale bars = 100 µm, 100 µm, 80 µm, and 20 µm for A, B, C, and G, respectively.</p

Prenatal stress decreases adult hippocampal neurogenesis.

<p>(A) Illustration of Ki67-IR cells in the DG in NS and PS groups. (B) Illustration of CldU-IR cells in the DG in NS and PS groups. (C) Illustration of DCX-IR cells in the DG in NS and PS groups. (D) Number of Ki67-IR cells in the DG, n = 10–14 per group. (E) Number of 5-week-old CldU-IR cells in the DG, n = 10–14 per group. (F) Number of DCX-IR cells in the DG, n = 10–14 per group. (G) Illustration of CldU-NeuN-IR cells (white arrow) and of CldU-S100-IR cells (white star). (H) Percentage of CldU-NeuN-IR cells in the DG, n = 5 per group. (I) Percentage of CldU-S100-IR cells in the DG, n = 5 per group. Scale bars = 100 µm, 100 µm, 50 µm, and 20 µm for A, B, C, and G, respectively.</p

Hippocampal Mossy Fibers Synapses in CA3 Pyramidal Cells Are Altered at an Early Stage in a Mouse Model of Alzheimer's Disease

International audienceEarly Alzheimer's disease (AD) affects the brain non-uniformly, causing hippocampal memory deficits long before widespread brain degeneration becomes evident. Here we addressed whether mossy fiber inputs from the dentate gyrus onto CA3 principal cells are affected in an AD mouse model before amyloid ␤ plaque deposition. We recorded from CA3 pyramidal cells in a slice preparation from 6-month-old male APP/PS1 mice, and studied synaptic properties and intrinsic excitability. In parallel we performed a morphometric analysis of mossy fiber synapses following viral based labeling and 3D-reconstruction. We found that the basal structural and functional properties as well as presynaptic short-term plasticity at mossy fiber synapses are unaltered at 6 months in APP/PS1 mice. However, transient potentiation of synaptic transmission mediated by activity-dependent release of lipids was abolished. Whereas the presynaptic form of mossy fiber long-term potentiation (LTP) was not affected, the postsynaptic LTP of NMDAR-EPSCs was reduced. In addition, we also report an impairment in feedforward inhibition in CA3 pyramidal cells. This study, together with our previous work describing deficits at CA3-CA3 synapses, provides evidence that early AD affects synapses in a projection-dependent manner at the level of a single neuronal population

Fabrication and characterization of thin self-rolling film for anti-inflammatory drug delivery

International audienceThin films have been identified as an alternative approach for targeting sensitive site as drug delivery tool. In this work, the preparation of self-rolling thin films to form tubes for wound healing and easy placement (e.g. in the colon via colonoscopy) have been studied. We explored the use of thin films as a protective dressing combined to local release of an anti-inflammatory in order to improve drug efficacy and limit the side effects of the oral route. Non-cytotoxic poly(ethylene) glycol and poly(lactic acid) photo-crosslinkable star copolymers were used for rapid UV crosslinking of bilayered films loaded with prednisolone. The films, crosslinked under UV lamp without the need of photoinitiator, are optimized and compared in terms of water uptake, swelling ratio, final tube diameter and morphology, anti-inflammatory drug loading and release. Our studies showed the spontaneous rolling of bilayer constructs directly after immersion in water. Tubular geometry allows application of the patch through minimally invasive procedures such as colonoscopy. Moreover, the rolled-up bilayers highlighted efficient release of encapsulated drug following Fickian diffusion mechanism. We also confirmed the anti-inflammatory activity of the released anti-inflammatory drug that inhibits the pro-inflammatory cytokine IL-1β in RAW 264.7 macrophages stimulated by Escherichia coli (E. coli)