Sexual dimorphism of AMBRA1-related autistic features in human and mouse.

Ambra1 is linked to autophagy and neurodevelopment. Heterozygous Ambra1 deficiency induces autism-like behavior in a sexually dimorphic manner. Extraordinarily, autistic features are seen in female mice only, combined with stronger Ambra1 protein reduction in brain compared to males. However, significance of AMBRA1 for autistic phenotypes in humans and, apart from behavior, for other autism-typical features, namely early brain enlargement or increased seizure propensity, has remained unexplored. Here we show in two independent human samples that a single normal AMBRA1 genotype, the intronic SNP rs3802890-AA, is associated with autistic features in women, who also display lower AMBRA1 mRNA expression in peripheral blood mononuclear cells relative to female GG carriers. Located within a non-coding RNA, likely relevant for mRNA and protein interaction, rs3802890 (A versus G allele) may affect its stability through modification of folding, as predicted by in silico analysis. Searching for further autism-relevant characteristics in Ambra1+/- mice, we observe reduced interest of female but not male mutants regarding pheromone signals of the respective other gender in the social intellicage set-up. Moreover, altered pentylentetrazol-induced seizure propensity, an in vivo readout of neuronal excitation-inhibition dysbalance, becomes obvious exclusively in female mutants. Magnetic resonance imaging reveals mild prepubertal brain enlargement in both genders, uncoupling enhanced brain dimensions from the primarily female expression of all other autistic phenotypes investigated here. These data support a role of AMBRA1/Ambra1 partial loss-of-function genotypes for female autistic traits. Moreover, they suggest Ambra1 heterozygous mice as a novel multifaceted and construct-valid genetic mouse model for female autism.

Intrauterine hyperexposure to dexamethasone of the common marmoset monkey revealed normal cerebral metabolite concentrations in adulthood as assessed by quantitative proton magnetic resonance spectroscopy in vivo.

BACKGROUND: Animal models of human brain disorders often have to rely on non-human primates because of their immunological, physiological, and cognitive similarities to humans. METHODS: Localized proton magnetic resonance spectroscopy was performed to assess cerebral metabolite profiles of male common marmoset monkeys in vivo and to determine putative alterations of adult brain metabolism in response to intrauterine hyperexposure to the synthetic glucocorticoid hormone dexamethasone. RESULTS: Excellent spectral quality allowed for absolute quantification of the concentrations of major metabolites in predominantly white matter, gray matter, and thalamus. Marmoset monkeys intrauterinely hyperexposed to dexamethasone revealed normal neurochemical profiles at adulthood. CONCLUSIONS: Prenatally applied dexamethasone does not lead to persistent metabolic alterations affecting adult brain integrity.

Compatibility of glass-guided recording microelectrodes in the brain stem of squirrel monkeys with high-resolution 3D MRI.

Knowledge of the precise position of recording microelectrodes within the brain of a non-human primate is essential for a reliable exploration of very small anatomic structures. This work demonstrates the compatibility of a newly developed glass-guided microelectrode design and microfeed equipment with high-resolution 3D magnetic resonance imaging (MRI). T1- and T2-weighted images allow for the non-invasive visualization of chronically implanted microelectrodes within the brain stem of squirrel monkeys in vivo. Neural extracellular multi-unit recordings proved the functionality of the microelectrode before and after the use of 3D MRI suggesting the preservation of normal brain tissue at the tip of the electrode. Because histology confirmed the absence of lesions attributable to MRI, the approach offers an interactive monitoring during the course of neuroethological experiments. Consequently, MRI may become an in vivo alternative to common histological post mortem verifications of electrode tracks and hence may avoid the early sacrificing of primates after only a small number of experiments.

In vivo diffusion tensor mapping of the brain of squirrel monkey, rat, and mouse using single-shot STEAM MRI.

The purpose was to assess the potential of half Fourier diffusion-weighted single-shot STEAM MRI for diffusion tensor mapping of animal brain in vivo. A STEAM sequence with image acquisition times of about 500 ms was implemented at 2.35 T using six gradient orientations and b values of 200, 700, and 1200 s mm(-2). The use of half Fourier phase-encoding increased the signal-to-noise ratio by 45% relative to full Fourier acquisitions. Moreover, STEAM-derived maps of the relative anisotropy and main diffusion direction were completely free of susceptibility-induced signal losses and geometric distortions. Within measuring times of 3 h, the achieved resolution varied from 600x700x1000 microm3 for squirrel monkeys to 140x280x720 microm3 for mice. While in monkeys the accessible white matter fiber connections were comparable to those reported for humans, detectable fiber structures in mice focused on the corpus callosum, anterior commissure, and hippocampal fimbria. In conclusion diffusion-weighted single-shot STEAM MRI allows for in vivo diffusion tensor mapping of the brain of squirrel monkeys, rats, and mice without motion artifacts and susceptibility distortions.

Laboratory experiments in atmospheric optics.

Old and new laboratory experiments on atmospheric optics with a focus on mirages, rainbows, and halos are presented. Some qualitative demonstrations serve primarily didactical purposes, e.g., by proving the existence of curved light rays in media with a gradient of the index of refraction, by directly visualizing the minimum-deviation curve for rainbow paths in water droplets, or by helping to elucidate the ray classes in hexagons that contribute to a specific halo. In addition, quantitative experiments allow a direct comparison of angular positions and intensities with analytical computations or Monte Carlo simulations of light scattering from small water droplets or ice hexagons. In particular, the latter can help us to understand complex halo phenomena.

Laboratory experiments in atmospheric optics.

Old and new laboratory experiments on atmospheric optics with a focus on mirages, rainbows, and halos are presented. Some qualitative demonstrations serve primarily didactical purposes, e.g., by proving the existence of curved light rays in media with a gradient of the index of refraction, by directly visualizing the minimum-deviation curve for rainbow paths in water droplets, or by helping to elucidate the ray classes in hexagons that contribute to a specific halo. In addition, quantitative experiments allow a direct comparison of angular positions and intensities with analytical computations or Monte Carlo simulations of light scattering from small water droplets or ice hexagons. In particular, the latter can help us to understand complex halo phenomena.

Immunohistological demonstration of feline infectious peritonitis virus antigen in paraffin-embedded tissues using feline ascites or murine monoclonal antibodies.

Feline infectious peritonitis (FIP) virus antigen was demonstrated after methanol, ethanol or formalin fixation in paraffin-embedded tissues by means of monoclonal and polyclonal antibodies. The monoclonal antibody was induced by immunization with transmissible gastroenteritis virus. Polyclonal antibodies were obtained by purification on protein A-Sepharose of ascites fluid from a cat with FIP. Almost all cats diagnosed as suffering from FIP by postmortem and histological examination exhibited FIP virus (FIPV) antigen in macrophages in granulomas whereas FIPV antigen was only once demonstrable in another location.