Excessive self-grooming, gene dysregulation and imbalance between the striosome and matrix compartments in the striatum of Shank3 mutant mice.

Autism is characterized by atypical social communication and stereotyped behaviors. Mutations in the gene encoding the synaptic scaffolding protein SHANK3 are detected in 1-2% of patients with autism and intellectual disability, but the mechanisms underpinning the symptoms remain largely unknown. Here, we characterized the behavior of Shank3 Δ11/Δ11 mice from 3 to 12 months of age. We observed decreased locomotor activity, increased stereotyped self-grooming and modification of socio-sexual interaction compared to wild-type littermates. We then used RNAseq on four brain regions of the same animals to identify differentially expressed genes (DEGs). DEGs were identified mainly in the striatum and were associated with synaptic transmission (e.g., Grm2, Dlgap1), G-protein-signaling pathways (e.g., Gnal, Prkcg1, and Camk2g), as well as excitation/inhibition balance (e.g., Gad2). Downregulated and upregulated genes were enriched in the gene clusters of medium-sized spiny neurons expressing the dopamine 1 (D1-MSN) and the dopamine 2 receptor (D2-MSN), respectively. Several DEGs (Cnr1, Gnal, Gad2, and Drd4) were reported as striosome markers. By studying the distribution of the glutamate decarboxylase GAD65, encoded by Gad2, we showed that the striosome compartment of Shank3 Δ11/Δ11 mice was enlarged and displayed much higher expression of GAD65 compared to wild-type mice. Altogether, these results indicate altered gene expression in the striatum of Shank3-deficient mice and strongly suggest, for the first time, that the excessive self-grooming of these mice is related to an imbalance in the striatal striosome and matrix compartments.

Surfactant induced gelation of TEMPO-oxidized cellulose nanofibril dispersions probed using small angle neutron scattering.

In this work, we studied TEMPO-oxidized cellulose nanofibril (OCNF) suspensions in the presence of diverse surfactants. Using a combination of small angle neutron scattering (SANS) and rheology, we compared the physical properties of the suspensions with their structural behavior. Four surfactants were studied, all with the same hydrophobic tail length but different headgroups: hexaethylene glycol mono-n-dodecyl ether (C12EO6, nonionic), sodium dodecyl sulfate (SDS, anionic), cocamidopropyl betaine (CapB, zwitterionic), and dodecyltrimethylammonium bromide (DTAB, cationic). Contrast variation SANS studies using deuterated version of C12EO6 or SDS, or by varying the D2O/H2O ratio of the suspensions (with CapB), allowed focusing only on the structural properties of OCNFs or surfactant micelles. We showed that, in the concentration range studied, for C12EO6, although the nanofibrils are concentrated thanks to an excluded volume effect observed in SANS, the rheological properties of the suspensions are not affected. Addition of SDS or CapB induces gelation for surfactant concentrations superior to the critical micellar concentration (CMC). SANS results show that attractive interactions between OCNFs arise in the presence of these anionic or zwitterionic surfactants, hinting at depletion attraction as the main mechanism of gelation. Finally, addition of small amounts of DTAB (below the CMC) allows formation of a tough gel by adsorbing onto the OCNF surface.

Validation of memory assessment in the Starmaze task: Data from 14 month-old APPPS1 mice and controls.

This article describes navigation data of 14 month-old APPPS1 and C57Bl6 in the Starmaze task. These data were acquired as positive controls of memory deficit in a model of the familial form of Alzheimers's disease (see Schmitt et al., Flexibility as a marker of early cognitive decline in humanized Apolipoprotein E ε4 (ApoE4) mice, Neurobiol Aging, 2021). They were acquired in a reduced version of the Starmaze environment and accompanied by a number of acquisitions in different control groups at 6 and 14 months to assess the robustness of the procedure and its associated memory scores. These data illustrate the extraction of a variety of navigation scores (including search strategy, spatial learning and memory) and provide a reference of navigation data in the Starmaze task for healthy 6-month-old controls, normal aging and a model of pathological memory deficit.

Salt-Responsive Pickering Emulsions Stabilized by Functionalized Cellulose Nanofibrils.

Oil-in-water emulsions have been stabilized by functionalized cellulose nanofibrils bearing either a negative (oxidized cellulose nanofibrils, OCNF) or a positive (cationic cellulose nanofibrils, CCNF) surface charge. The size of the droplets was measured by laser diffraction, while the structure of the shell of the Pickering emulsion droplets was probed using small-angle neutron scattering (SANS), confocal laser scanning microscopy (CLSM), scanning electron microscopy (SEM), and rheology measurements. Both OCNF- and CCNF-stabilized emulsions present a very thick shell (>100 nm) comprised of densely packed CNF. OCNF-stabilized emulsions proved to be salt responsive, influencing the droplet aggregation and ultimately the gel properties of the emulsions, while CCNF emulsions, on the other hand, showed very little salt-dependent behavior.

Monovalent Salt and pH-Induced Gelation of Oxidised Cellulose Nanofibrils and Starch Networks: Combining Rheology and Small-Angle X-ray Scattering.

Water quality parameters such as salt content and various pH environments can alter the stability of gels as well as their rheological properties. Here, we investigated the effect of various concentrations of NaCl and different pH environments on the rheological properties of TEMPO-oxidised cellulose nanofibril (OCNF) and starch-based hydrogels. Addition of NaCl caused an increased stiffness of the OCNF:starch (1:1 wt%) blend gels, where salt played an important role in reducing the repulsive OCNF fibrillar interactions. The rheological properties of these hydrogels were unchanged at pH 5.0 to 9.0. However, at lower pH (4.0), the stiffness and viscosity of the OCNF and OCNF:starch gels appeared to increase due to proton-induced fibrillar interactions. In contrast, at higher pH (11.5), syneresis was observed due to the formation of denser and aggregated gel networks. Interactions as well as aggregation behaviour of these hydrogels were explored via ζ-potential measurements. Furthermore, the nanostructure of the OCNF gels was probed using small-angle X-ray scattering (SAXS), where the SAXS patterns showed an increase of slope in the low-q region with increasing salt concentration arising from aggregation due to the screening of the surface charge of the fibrils.

Flexibility as a marker of early cognitive decline in humanized apolipoprotein E ε4 (ApoE4) mice.

To test the hypothesis that ApoE4 may be involved in cognitive deficits associated with aging, we investigated the impact of APOE4 status and aging on the flexibility and memory components of spatial learning in mice. Young adult (6 months) and middle-aged (14 months) ApoE4, ApoE3 and C57BL/6 male mice were tested for flexibility in an aquatic Y-maze, and for spatio-temporal memory acquisition in the Starmaze. Our results revealed a flexibility deficit of the 6-month-old ApoE4 mice compared to controls. However, this deficit was not associated with spatio-temporal memory deficit at the same age. Importantly, the ApoE4 flexibility deficit did not increase with age, nor turn into memory deficit, or was able to predict individual variations of memory performance at 14 months. By contrast, control ApoE3 mice showed a decline of flexibility at 14 months resulting in performance similar to that of ApoE4. Overall, our results suggest that ApoE4 could be associated with an acceleration of the flexibility decrease otherwise observed in normal aging.

Self-assembly of amphiphilic polyoxometalates for the preparation of mesoporous polyoxometalate-titania catalysts.

Amphiphilic polyoxometalate (POM) surfactants were prepared by covalently grafting double hydrophobic tails with chain lengths C12H25, C14H29, C16H33 or C18H37 onto the lacunary Wells-Dawson {P2W17O61} headgroup. The critical micelle concentrations (CMCs) of these novel surfactants in aqueous solutions were determined by conductivity, and micelle formation was studied by small angle neutron scattering (SANS). Surprisingly, the amphiphiles with longer hydrophobic tails tend to form less elongated and more globular micelles in water. The self-assembled amphiphilic polyoxometalates were used as templates in the hydrothermal synthesis of mesoporous TiO2 containing dispersed, immobilised {P2W17O61} units, which showed enhanced activity for the photodegradation of rhodamine B (RhB). The catalyst was recycled eight times with no loss of efficiency, demonstrating the stability of the hybrid structure. The amphiphilic polyoxometalates, therefore have excellent potential for the synthesis of various types of catalytically active porous materials.

Antagonistic mixing in micelles of amphiphilic polyoxometalates and hexaethylene glycol monododecyl ether.

HYPOTHESIS: Polyoxometalates (POMs) are metal oxygen clusters with a range of interesting magnetic and catalytic properties. POMs with attached hydrocarbon chains show amphiphilic behaviour so we hypothesised that mixtures of a nonionic surfactant and anionic surfactants with a polyoxometalate cluster as headgroup would form mixed micelles, giving control of the POM density in the micelle, and which would differ in size and shape from micelles formed by the individual surfactants. Due to the high charge and large size of the POM, we suggested that these would be nonideal mixtures due to the complex interactions between the two types of surfactants. The nonideality and the micellar composition may be quantified using regular solution theory. With supplementary information provided by small-angle neutron scattering (SANS), an understanding of this unusual binary surfactant system can be established. EXPERIMENTS: A systematic study was performed on mixed surfactant systems containing polyoxometalate-headed amphiphiles (K10[P2W17O61OSi2(CnH2n+1)2], abbreviated as P2W17-2Cn, where n = 12, 14 or 16) and hexaethylene glycol monododecyl ether (C12EO6). Critical micelle concentrations (CMCs) of these mixtures were measured and used to calculate the interaction parameters based on regular solution theory, enabling prediction of micellar composition. Predictions were compared to micelle structures obtained from SANS. A phase diagram was also established. FINDINGS: The CMCs of these mixtures suggest unusual unfavourable interactions between the two species, despite formation of mixed micelles. Micellar compositions obtained from SANS concurred with those calculated using the averaged interaction parameters for P2W17-2Cn/C12EO6 (n = 12 and 14). We attribute the unfavourable interactions to a combination of different phenomena: counterion-mediated interactions between P2W17 units and the unfolding of the ethylene oxide headgroups of the nonionic surfactant, yet micelles still form in these systems due to the hydrophobic interactions between surfactant tails.

Impact of wormlike micelles on nano and macroscopic structure of TEMPO-oxidized cellulose nanofibril hydrogels.

In this work, we investigated the effect of adding surfactant mixtures on the rheological properties of TEMPO-oxidized cellulose nanofibril (OCNF) saline dispersions. Three surfactant mixtures were studied: cocamidopropyl betaine (CAPB)/sodium dodecyl sulfate (SDS), which forms wormlike micelles (WLMs); cocamidopropylamine oxide (CAPOx)/SDS, which forms long rods; and CAPB/sodium lauroyl sarcosinate (SLS), which forms spherical micelles. The presence of micelles in these surfactant mixtures, independent of their morphology, leads to an increase of tan δ, making the gels less solid-like, therefore acting as a plasticizer. WLMs were able to suppress strain stiffening normally observed in OCNF gels at large strains. OCNF/WLM gels have lower G' values than OCNF gels while the other micellar morphologies have a reduced impact on G'. The presence of unconnected micelles leads to increased dissipative deformation in OCNF gels without affecting the connectivity of the fibrils, while the presence of entangled micelles interferes with the OCNF network.

Mesoporous Silica Formation Mechanisms Probed Using Combined Spin-Echo Modulated Small-Angle Neutron Scattering (SEMSANS) and Small-Angle Neutron Scattering (SANS).

The initial formation stages of surfactant-templated silica thin films which grow at the air-water interface were studied using combined spin-echo modulated small-angle neutron scattering (SEMSANS) and small-angle neutron scattering (SANS). The films are formed from either a cationic surfactant or nonionic surfactant (C16EO8) in a dilute acidic solution by the addition of tetramethoxysilane. Previous work has suggested a two stage formation mechanism with mesostructured particle formation in the bulk solution driving film formation at the solution surface. From the SEMSANS data, it is possible to pinpoint accurately the time associated with the formation of large particles in solution that go on to form the film and to show their emergence is concomitant with the appearance of Bragg peaks in the SANS pattern, associated with the two-dimensional hexagonal order. The combination of SANS and SEMSANS allows a complete depiction of the steps of the synthesis that occur in the subphase.

Core-Shell Spheroidal Hydrogels Produced via Charge-Driven Interfacial Complexation.

Through charge-driven interfacial complexation, we produced millimeter-sized spheroidal hydrogels (SH) with a core-shell structure allowing long-term stability in aqueous media. The SH were fabricated by extruding, dropwise, a cationic cellulose nanofibril (CCNF) dispersion into an oppositely charged poly(acrylic acid) (PAA) bath. The SH have a solid-like CCNF-PAA shell, acting as a semipermeable membrane, and a liquid-like CCNF suspension in the core. Swelling behavior of the SH was dependent on the osmotic pressure of the aging media. Swelling could be suppressed by increasing the ionic strength of the media as this enhanced interfibrillar interactions and thus strengthened the outer gel membrane. We further validated a potential application of SH as reusable matrixes for glucose oxidase (GOx) entrapment, where the SH work as microreactors from which substrate and product are freely able to migrate through the SH shell while avoiding enzyme leakage.

Cationic surfactants as a non-covalent linker for oxidised cellulose nanofibrils and starch-based hydrogels.

Rheological properties of hydrogels composed of TEMPO-oxidised cellulose nanofibrils (OCNF)-starch in the presence of cationic surfactants were investigated. The cationic surfactants dodecyltrimethylammonium bromide (DTAB) and cetyltrimethylammonium bromide (CTAB) were used to trigger gelation of OCNF at around 5 mM surfactant. As OCNF and DTAB/CTAB are oppositely charged, an electrostatic attraction is suggested to explain the gelation mechanism. OCNF (1 wt%) and soluble starch (0.5 and 1 wt%) were blended to prepare hydrogels, where the addition of starch to the OCNF resulted in a higher storage modulus. Starch polymers were suggested to form networks with cellulose nanofibrils. The stiffness and viscosity of OCNF-Starch hydrogels were enhanced further by the addition of cationic surfactants (5 mM of DTAB/CTAB). ζ -potential and amylose-iodine complex analyses were also conducted to confirm surface charge and interaction of OCNF-starch-surfactant in order to provide an in-depth understanding of the surfactant-induced gel networks.

Hydrophobization of Cellulose Nanocrystals for Aqueous Colloidal Suspensions and Gels.

Surface hydrophobization of cellulose nanomaterials has been used in the development of nanofiller-reinforced polymer composites and formulations based on Pickering emulsions. Despite the well-known effect of hydrophobic domains on self-assembly or association of water-soluble polymer amphiphiles, very few studies have addressed the behavior of hydrophobized cellulose nanomaterials in aqueous media. In this study, we investigate the properties of hydrophobized cellulose nanocrystals (CNCs) and their self-assembly and amphiphilic properties in suspensions and gels. CNCs of different hydrophobicity were synthesized from sulfated CNCs by coupling primary alkylamines of different alkyl chain lengths (6, 8, and 12 carbon atoms). The synthetic route permitted the retention of surface charge, ensuring good colloidal stability of hydrophobized CNCs in aqueous suspensions. We compare surface properties (surface charge, ζ potential), hydrophobicity (water contact angle, microenvironment probing using pyrene fluorescence emission), and surface activity (tensiometry) of different hydrophobized CNCs and hydrophilic CNCs. Association of hydrophobized CNCs driven by hydrophobic effects is confirmed by X-ray scattering (SAXS) and autofluorescent spectroscopy experiments. As a result of CNC association, CNC suspensions/gels can be produced with a wide range of rheological properties depending on the hydrophobic/hydrophilic balance. In particular, sol-gel transitions for hydrophobized CNCs occur at lower concentrations than hydrophilic CNCs, and more robust gels are formed by hydrophobized CNCs. Our work illustrates that amphiphilic CNCs can complement associative polymers as modifiers of rheological properties of water-based systems.

Anisotropic mesoporous silica/microgel core-shell responsive particles.

Hybrid anisotropic microgels were synthesised using mesoporous silica as core particles. By finely controlling the synthesis conditions, the latter can be obtained with different shapes such as platelets, primary particles or rods. Using the core particles as seeds for precipitation polymerisation, a crosslinked poly(N-isopropylacrylamide) (PNIPAM) microgel shell could be grown at the surface, conferring additional thermo-responsive properties. The different particles were characterised using scattering and imaging techniques. Small angle X-ray scattering (SAXS) was employed to identify the shape and porous organisation of the core particles and dynamic light scattering (DLS) to determine the swelling behaviour of the hybrid microgels. In addition, cryogenic transmission electron microscopy (cryo-TEM) imaging of the hybrids confirms the different morphologies as well as the presence of the microgel network and the core-shell conformation. Finally, the response of the particles to an alternating electric field is demonstrated for hybrid rod-shaped microgels in situ using confocal laser scanning microscopy (CLSM).

Charge-driven interfacial gelation of cellulose nanofibrils across the water/oil interface.

Interfacial gels, obtained by the interaction of water-dispersible oxidised cellulose nanofibrils (OCNF) and oil-soluble oleylamine (OA), were produced across water/oil (W/O) interfaces. Surface rheology experiments showed that the complexation relies on the charge coupling between the negatively-charged OCNF and OA. Complexation across the W/O interface was found to be dependent on the ζ-potential of the OCNF (modulated by electrolyte addition), leading to different interfacial properties. Spontaneous OCNF adsorption at the W/O interface occurred for particles with ζ-potential more negative than -30 mV, resulting in the formation of interfacial gels; whilst for particles with ζ-potential of ca. -30 mV, spontaneous adsorption occurred, coupled with augmented interfibrillar interactions, yielding stronger and tougher interfacial gels. On the contrary, charge neutralisation of OCNF (ζ-potential values more positive than -30 mV) did not allow spontaneous adsorption of OCNF at the W/O interface. In the case of favourable OCNF adsorption, the interfacial gel was found to embed oil-rich droplets - a spontaneous emulsification process.

Soft particles in an electric field - a zero average contrast study.

We report on the structural properties of ionic microgel particles subjected to alternating electric fields, using small-angle neutron scattering. The experiments were performed under so-called zero average contrast conditions, which cancel the structure factor contribution to the scattered intensity, allowing us to obtain direct information on the single particle size and structure as particles align in field-induced strings. Our results reveal only a marginal compression of the particles as they align in strings, and indicate considerable particle overlap at higher field strengths. These findings provide further insight into the origins of the previously reported unusual path dependent field-induced crystal-crystal transition found for these systems (P. S. Mohanty et al., Phys. Rev. X, 2015, 5, 011030).

PKR knockout in the 5xFAD model of Alzheimer's disease reveals beneficial effects on spatial memory and brain lesions.

Brain lesions in Alzheimer's disease (AD) include amyloid plaques made of Aß peptides and neurofibrillary tangles composed of hyperphosphorylated tau protein with synaptic and neuronal loss and neuroinflammation. Aß oligomers can trigger tau phosphorylation and neuronal alterations through activation of neuronal kinases leading to progressive cognitive decline. PKR is a ubiquitous pro-apoptotic serine/threonine kinase, and levels of activated PKR are increased in AD brains and AD CSF. In addition, PKR regulates negatively memory formation in mice. To assess the role of PKR in an AD in vivo model, we crossed 5xFAD transgenic mice with PKR knockout (PKRKO) mice and we explored the contribution of PKR on cognition and brain lesions in the 5xFAD mouse model of AD as well as in neuron-microglia co-cultures exposed to the innate immunity activator lipopolysaccharide (LPS). Nine-month-old double-mutant mice revealed significantly improved memory consolidation with the new object location test, starmaze test, and elevated plus maze test as compared to 5xFAD mice. Brain amyloid accumulation and BACE1 levels were statistically decreased in double-mutant mice. Apoptosis, neurodegeneration markers, and synaptic alterations were significantly reduced in double-mutant mice as well as neuroinflammation markers such as microglial load and brain cytokine levels. Using cocultures, we found that PKR in neurons was essential for LPS microglia-induced neuronal death. Our results demonstrate the clear involvement of PKR in abnormal spatial memory and brain lesions in the 5xFAD model and underline its interest as a target for neuroprotection in AD.

Understanding heat driven gelation of anionic cellulose nanofibrils: Combining saturation transfer difference (STD) NMR, small angle X-ray scattering (SAXS) and rheology.

A novel mechanism of heat-triggered gelation for oxidised cellulose nanofibrils (OCNF) is reported. We demonstrate that a synergistic approach combining rheology, small-angle X-ray scattering (SAXS) and saturation transfer difference NMR (STD NMR) experiments enables a detailed characterisation of gelation at different length scales. OCNF dispersions experience an increase in solid-like behaviour upon heating as evidenced by rheological studies, associated with enhanced interfibrillar interactions measured using SAXS. Interactions result in an increased fibrillar overlap and increased population of confined water molecules monitored by STD NMR. In comparison, cationic cellulose nanofibrils (produced by reaction of cellulose with trimethylglycidylammonium chloride) were found to be heat-unresponsive.

Alcohol induced gelation of TEMPO-oxidized cellulose nanofibril dispersions.

Solvent-induced physical hydrogels of TEMPO-oxidized cellulose nanofibrils (OCNFs) were obtained from aqueous/alcoholic dispersions of fibrils in lower alcohols, namely, methanol, ethanol, 1-propanol and 2-propanol. The sol-gel transition occurs above a critical alcohol concentration of ca. 30 wt% for all alcohols tested. The rheological properties of the hydrogels depend on the nature of the alcohol: for ethanol, 1-propanol and 2-propanol the magnitude of the shear storage modulus follows the alcohol hydrophilicity, whilst methanol produces the weakest gels in the group. Above a second critical concentration, ca. 60 wt% alcohol, phase separation is observed as the gels undergo syneresis. Analysis of small-angle X-ray scattering data shows that the OCNFs may be modelled as rigid rods. In the presence of lower alcohols, attractive interactions between nanofibrils are present and, above the alcohol concentration leading to gelation, an increase of the OCNF cross-section is observed, suggesting alcohol induced aggregation of nanofibrils.

Surfactant controlled zwitterionic cellulose nanofibril dispersions.

Zwitterionic cellulose nanofibrils (ZCNFs) with an isoelectric point of 3.4 were obtained by grafting glycidyltrimethylammonium chloride onto TEMPO/NaBr/NaOCl-oxidised cellulose nanofibrils. The ZCNF aqueous dispersions were characterized via transmission electron microscopy, rheology and small angle neutron scattering, revealing a fibril-bundle structure with pronounced aggregation at pH 7. Surfactants were successfully employed to tune the stability of the ZCNF dispersions. Upon addition of the anionic surfactant, sodium dodecyl sulfate, the ZCNF dispersion shows individualized fibrils due to electrostatic stabilization. In contrast, upon addition of the cationic species dodecyltrimethylammonium bromide, the dispersion undergoes charge neutralization, leading to more pronounced flocculation.