Dysregulation of microtubule stability impairs morphofunctional connectivity in primary neuronal networks

Functionally related neurons assemble into connected networks that process and transmit electrochemical information. To do this in a coordinated manner, the number and strength of synaptic connections is tightly regulated. Synapse function relies on the microtubule (MT) cytoskeleton, the dynamics of which are in turn controlled by a plethora of MT-associated proteins, including the MT-stabilizing protein Tau. Although mutations in the Tau-encodingMAPT gene underlie a set of neurodegenerative disorders, termed tauopathies, the exact contribution of MT dynamics and the perturbation thereof to neuronal network connectivity has not yet been scrutinized. Therefore, we investigated the impact of targeted perturbations of MT stability on morphological (e.g., neurite- and synapse density) and functional (e.g., synchronous calcium bursting) correlates of connectivity in networks of primary hippocampal neurons. We found that treatment with MT-stabilizing or -destabilizing compounds impaired morphofunctional connectivity in a reversible manner. We also discovered that overexpression of MAPT induced significant connectivity defects, which were accompanied by alterations in MT dynamics and increased resistance to pharmacological MT depolymerization. Overexpression of a MAPT variant harboring the P301L point mutation in the MT-binding domain did far less, directly linking neuronal connectivity with Tau's MT binding affinity. Our results show that MT stability is a vulnerable node in tauopathies and that its precise pharmacological tuning may positively affect neuronal network connectivity. However, a critical balance in MT turnover causes it to be a difficult therapeutic target with a narrow operating window

MOBIUS SYNDROME AND OBSESSIVE COMPULSIVE DISORDER: A CASE REPORT

Background: Mobius syndrome is characterized by a bilateral congenital paralysis of the facial and abducens nerves which leaves the subject with an expressionless "mask-like" face. Subjects and methods: Based on a literature review and a case discussion of an adult patient with Mobius syndrome and obsessive-compulsive disorder, initially undiagnosed and confused with a psychotic disorder, we will discuss the influence of Mobius syndrome in psychiatric evaluations. Results: The lack of facial expressiveness and non-verbal emotional interactions may influence psychiatric evaluations and result in misdiagnosis and the inappropriate prescribing of antipsychotics. In the case analysis, we also observed other associated malformations such as renal atrophy, a bicuspid aortic valve and mitral valve prolapse. Conclusion: We feel that educating the patient about the communicative consequences of impaired facial expressions and facial interactions is a necessary prerequisite for any psychiatric or psychological evaluation in subjects with Mobius syndrome. We also recommend using caution when prescribing antipsychotics in patients with Mobius syndrome given the motor side effects secondary to a potentially pre-existing hypotonia

Segmental distribution and morphometric features of primary sensory neurons projecting to the tibial periosteum in the rat.

Previous reports have demonstrated very rich innervation pattern in the periosteum. Most of the periosteal fibers were found to be sensory in nature. The aim of this study was to identify the primary sensory neurons that innervate the tibial periosteum in the adult rat and to describe the morphometric features of their perikarya. To this end, an axonal fluorescent carbocyanine tracer, DiI, was injected into the periosteum on the medial surface of the tibia. The perikarya of the sensory fibers were traced back in the dorsal root ganglia (DRG) L1-L6 by means of fluorescent microscopy on cryosections. DiI-containing neurons were counted in each section and their segmental distribution was determined. Using PC-assisted image analysis system, the size and shape of the traced perikarya were analyzed. DiI-labeled sensory neurons innervating the periosteum of the tibia were located in the DRG ipsilateral to the injection site, with the highest distribution in L3 and L4 (57% and 23%, respectively). The majority of the traced neurons were of small size (area < 850 microm2), which is consistent with the size distribution of CGRP- and SP-containing cells, regarded as primary sensory neurons responsible for perception of pain and temperature. A small proportion of labeled cells had large perikarya and probably supplied corpuscular sense receptors observed in the periosteum. No differences were found in the shape distribution of neurons belonging to different size classes

DEVELOPMENTAL CHANGES OF NO-ERGIC SYNAPTIC TRANSMISSION IN RAT SYMPATHETIC GANGLIA

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Identification and characterization of a type III secretion system in Chlamydophila psittaci

Chlamydiaceae are obligate intracellular Gram-negative bacteria replicating in vacuoles inside eukaryotic cells. It has been proven that most of them possess a type III secretion system (T3SS) allowing them to transfer effector molecules in the host cell. We examined the existence of a T3SS in Chlamydophila psittaci by studying the expression of three essential structural proteins SctW, SctC, and SctN, and one putative effector protein IncA. Immunofluorescence assays showed SctW and IncA to be associated with the bacteria and the inclusion membrane, while SctC and SctN were only localized to the bacteria itself. Immuno electron microscopy could confirm these results for SctW, IncA, and SctC. Unfortunately, SctN was not investigated with this technique. Additionally, we sequenced 14 full-length T3S genes (scc1, sctW, sctJ, sctL, sctR, sctS, scc2, copD1, sctN, sctQ, sctC, incA, ca037, and cadd) and examined the transcription of 26 Cp. psittaci T3S genes namely cluster 1 (scc1, sctW, sctV, sctU), cluster 2 (sctJ, sctL, sctR, sctS, sctT, scc2, copB1, copD1), cluster 3 (sctD, sctN, ca037, sctQ, pkn5, sctC) and non-clustered genes (incA, incC, scc3, copD2, cap1, tarp, ca530, cadd). The gene expression study indicated the T3S structural protein encoding genes to be transcribed from mid-cycle (12-18 h post infection (p.i.)) on. Genes encoding effector proteins and putative T3S related proteins were expressed early (1.5 h-8 h p.i.) or late (> 24 h p.i.) during the developmental cycle. We hereby provided evidence for the existence of a T3SS and possible effectors in avian Cp. psittaci

Prix Adolphe Wetrems (30e période annuelle, 1955-1956) : rapport sur les travaux de M. Paul Dedecker

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