Lifelong Impact of Variations in Maternal Care on Dendritic Structure and Function of Cortical Layer 2/3 Pyramidal Neurons in Rat Offspring

Maternal licking and grooming (LG) exerts profound influence on hippocampal development and function in the offspring. However, little information is available on the effects of variations in maternal care on other brain regions. Here we examined the effects of variation in the frequency of maternal LG on morphological and electrophysiological properties of layer 2/3 pyramidal neurons in the somatosensory cortex in adult offspring. Compared to low LG offspring, high LG offspring displayed decreased dendritic complexity, reduced spine density and decreased amplitude of spontaneous postsynaptic currents. These changes were accompanied by higher levels of reelin expression in offspring of high LG mothers. Taken together, these findings suggest that differential amount of naturally-occurring variations in maternal LG is associated with enduring changes in dendritic morphology and synaptic function in layer 2/3 pyramidal neurons of the somatosensory cortex

Impaired Social Behavior in 5-HT3A Receptor Knockout Mice

The 5-HT3 receptor is a ligand-gated ion channel expressed on interneurons throughout the brain. So far, analysis of the 5-HT3A knockout mouse revealed changes in nociceptive processing and a reduction in anxiety related behavior. Recently, it was shown that the 5-HT3 receptor is also expressed on Cajal-Retzius cells which play a key role in cortical development and that knockout mice lacking this receptor showed aberrant growth of the dendritic tree of cortical layer II/III pyramidal neurons. Other mouse models in which serotonergic signaling was disrupted during development showed similar morphological changes in the cortex, and in addition, also deficits in social behavior. Here, we subjected male and female 5-HT3A knockout mice and their non-transgenic littermates to several tests of social behavior. We found that 5-HT3A knockout mice display impaired social communication in the social transmission of food preference task. Interestingly, we showed that in the social interaction test only female 5-HT3A knockout mice spent less time in reciprocal social interaction starting after 5 min of testing. Moreover, we observed differences in preference for social novelty for male and female 5-HT3A knockout mice during the social approach test. However, no changes in olfaction, exploratory activity and anxiety were detected. These results indicate that the 5-HT3A knockout mouse displays impaired social behavior with specific changes in males and females, reminiscent to other mouse models in which serotonergic signaling is disturbed in the developing brain

Alterations in Apical Dendrite Bundling in the Somatosensory Cortex of 5-HT3A Receptor Knockout Mice

In various species and areas of the cerebral cortex, apical dendrites of pyramidal neurons form clusters which extend through several layers of the cortex also known as dendritic bundles. Previously, it has been shown that 5-HT3A receptor knockout mice show hypercomplex apical dendrites of cortical layer 2/3 pyramidal neurons, together with a reduction in reelin levels, a glycoprotein involved in cortical development. Other studies showed that in the mouse presubicular cortex, reelin is involved in the formation of modular structures. Here, we compare apical dendrite bundling in the somatosensory cortex of wildtype and 5-HT3A receptor knockout mice. Using a microtubule associated protein-2 immunostaining to visualize apical dendrites of pyramidal neurons, we compared dendritic bundle properties of wildtype and 5-HT3A receptor knockout mice in tangential sections of the somatosensory cortex. A Voronoi tessellation was performed on immunostained tangential sections to determine the spatial organization of dendrites and to define dendritic bundles. In 5-HT3A receptor knockout mice, dendritic bundle surface was larger compared to wildtype mice, while the number and distribution of reelin-secreting Cajal–Retzius cells was similar for both groups. Together with previously observed differences in dendritic complexity of cortical layer 2/3 pyramidal neurons and cortical reelin levels, these results suggest an important role for the 5-HT3 receptor in determining the spatial organization of cortical connectivity in the mouse somatosensory cortex

Safer Tripping: Serotonergic Psychedelics and Drug Checking. Submission and Detection Rates, Potential Harms, and Challenges for Drug Analysis

Purpose of Review With the continuous emergence of new psychoactive substances, drug checking (DC) services are challenged by an increasingly complex drug market. Considering the resumed scientific and public interest in serotonergic psychedelics (SPs) like LSD, psilocybin, and 2C-B, we present the results of a literature search investigating the presence and proportion of SPs in DC samples. Recent Findings: In 15 identified reports, submission and detection rates of SPs were comparably low, but increasing. Samples contained considerable amounts of adulterations or analogues, mostly novel SPs with unknown toxicological profiles and in some cases potentially life-threatening effects. The detection of SPs, however, requires advanced analysis techniques currently not available to most DC services. Summary: Given the substantial proportion of novel SPs in DC samples and the associated risks, DC can be a valuable harm reduction and monitoring tool for SPs if analysis techniques with high sensitivity are employed

Glycan-dependent immunogenicity of recombinant soluble trimeric hemagglutinin

Recombinant soluble trimeric influenza A virus (IAV) hemagglutinin (sHA3) has proven an effective vaccine antigen against IAV. Here, we investigate to what extent the glycosylation status of the sHA3 glycoprotein affects its immunogenicity. Different glycosylation forms of subtype H5 trimeric HA protein (sH53) were produced by expression in insect cells and different mammalian cells in the absence and presence of inhibitors of N-glycan-modifying enzymes or by enzymatic removal of the oligosaccharides. The following sH53 preparations were evaluated: (i) HA proteins carrying complex glycans produced in HEK293T cells; (ii) HA proteins carrying Man9GlcNAc2 moieties, expressed in HEK293T cells treated with kifunensine; (iii) HA proteins containing Man5GlcNAc2 moieties derived from HEK293S GnTI(-) cells; (iv) insect cell-produced HA proteins carrying paucimannosidic N-glycans; and (v) HEK293S GnTI(-) cell-produced HA proteins treated with endoglycosidase H, thus carrying side chains composed of only a single N-acetylglucosamine each. The different HA glycosylation states were confirmed by comparative electrophoretic analysis and by mass spectrometric analysis of released glycans. The immunogenicity of the HA preparations was studied in chickens and mice. The results demonstrate that HA proteins carrying terminal mannose moieties induce significantly lower hemagglutination inhibition antibody titers than HA proteins carrying complex glycans or single N-acetylglucosamine side chains. However, the glycosylation state of the HA proteins did not affect the breadth of the antibody response as measured by an HA1 antigen microarray. We conclude that the glycosylation state of recombinant antigens is a factor of significant importance when developing glycoprotein-based vaccines, such as recombinant HA proteins

Size Matters: Comparing the MDMA content and weight of ecstasy tablets submitted to European drug checking services in 2012-2021

Purpose The 3,4-methylenedioxymetamphetamine (MDMA) content in ecstasy tablets has increased enormously throughout Europe across the past decade. This study aims to determine whether this is caused by the production of “stronger” tablets (more mg MDMA per mg of tablet), or if tablets have simply been getting larger and heavier (more mg of tablet in total). Design/methodology/approach A data set of 31,716 ecstasy tablets obtained in 2012–2021 by 10 members of the Trans European Drug Information (TEDI) network was analysed. Findings The MDMA mass fraction in ecstasy tablets has remained virtually unchanged over the past 10 years, with increased MDMA contents being attributed almost exclusively to increased tablet weight. These trends seem to be uniform across Europe, despite varying sampling and analytical techniques being used by the TEDI participants. The study also shows that while tablet weight correlates perfectly with MDMA content on a yearly basis, wide variations in the MDMA mass fraction make such relations irrelevant for determining the MDMA content of individual tablets. Research limitations/implications These results provide new opportunities for harm reduction, given that size is a tangible and apparently accurate characteristic to emphasise that one tablet does not simply equate to one dose. This is particularly useful for harm reduction services without the resources for in-house quantification of large numbers of ecstasy tablets, although the results of this study also show that chemical analysis remains crucial for accurate personalised harm reduction. Originality/value The findings are both new and pertinent, providing a novel insight into the market dynamics of ecstasy tablet production at a transnational level

Methodological advances in imaging intravital axonal transport.

Axonal transport is the active process whereby neurons transport cargoes such as organelles and proteins anterogradely from the cell body to the axon terminal and retrogradely in the opposite direction. Bi-directional transport in axons is absolutely essential for the functioning and survival of neurons and appears to be negatively impacted by both aging and diseases of the nervous system, such as Alzheimer's disease and amyotrophic lateral sclerosis. The movement of individual cargoes along axons has been studied in vitro in live neurons and tissue explants for a number of years; however, it is currently unclear as to whether these systems faithfully and consistently replicate the in vivo situation. A number of intravital techniques originally developed for studying diverse biological events have recently been adapted to monitor axonal transport in real-time in a range of live organisms and are providing novel insight into this dynamic process. Here, we highlight these methodological advances in intravital imaging of axonal transport, outlining key strengths and limitations while discussing findings, possible improvements, and outstanding questions