Volume 25, Issue 3

Zusammenfassung Mikroglia sind Zellen des angeborenen Immunsystems im zentralen Nervensystem, die eine bedeutende Rolle bei entzündlichen Veränderungen im Nervengewebe spielen. Ursprünglich galt die Annahme, dass Mikrogliazellen ihre Funktion erst nach Aktivierung durch pathologische Stimuli aufnehmen. Neuere Studien deuten darauf hin, dass Mikroglia physiologische Funktionen bei neuronalen Entwicklungsprozessen oder synaptischen Anpassungsreaktionen hat. Basierend auf dem Konzept, dass die Freisetzung mikroglialer Faktoren synaptische Eigenschaften tripartiter Synapsen (Präsynapse, Postsynapse, Astrozyt) beeinflussen kann, wurde der Begriff der neuroimmunologischen Synapse geprägt. Unter Bedingungen, bei denen der Aktivitätszustand der Mikroglia durch endogene oder exogene pathologische Stimuli verändert wird, kann dadurch das physiologische Zusammenspiel von Mikroglia, Astrozyten und Nervenzellen an Synapsen gestört sein, wodurch krankhafte Prozesse im zentralen Nervensystem angestoßen, befördert oder erhalten werden können.

Stroke is one of the leading causes of mortality and morbidity worldwide. Upon cerebral ischemia, an inflammatory reaction takes place in the brain. Infiltration of different immune cell subsets as well as activation of resident microglia cells have been shown to have both beneficial and detrimental effects on stroke outcome. For a long time, research in the field of adaptive immunity after stroke has mostly focused on T lymphocytes and only recently, several publications shed light on the importance of B lymphocytes in the acute and chronic phases of ischemic stroke. In this review, we will focus on the role of B cells in the ischemic brain and describe possible antibody-dependent and antibody-independent mechanisms in the development of post-stroke cognitive deficits.

RNA-sensing Toll-like receptors (TLRs) are mostly associated with the recognition of viruses. However, over the last years it has become clear that the function and relevance of these receptors are far more complex. They are essential for the recognition of bacteria, fungi and parasites, leading to transcriptional activation of central nervous system (CNS) resident and invading myeloid cells during infectious meningitis and encephalitis. Moreover, host-derived RNA species interact with TLRs. Injured CNS neurons release small RNAs, e. g. microRNAs, into the extracellular space. Neighboring neurons and microglia take up these RNA molecules via the endosomal route, which provides the opportunity for activation of endosomal TLRs. This process contributes to neuroinflammation and further neuronal injury, thus closing the vicious cycle of CNS damage, as it may occur in numerous CNS disorders including neurodegenerative diseases.

The cellular composition of the central nervous system (CNS) is highly complex and dynamic. Regulation of this complexity is increasingly recognized to be spatially and temporally dependent during development, homeostasis and disease. Context-dependent cellular heterogeneity was shown for neuroectodermal cells as well as the myeloid compartment of the CNS. The brain myeloid compartment comprises microglia and other CNS-associated macrophages. These are brain-resident cells with critical roles in brain development, maintenance, and immune responses during states of disease. Profiling of CNS myeloid cell heterogeneity has been greatly facilitated in the past years by development of high-throughput technologies for single-cell analysis. This review summarizes current insights into heterogeneity of the CNS myeloid cell population determined by single-cell RNA sequencing and mass cytometry. The results offer invaluable insights into CNS biology and will facilitate the development of therapies for neurodegenerative and neuroinflammatory pathologies.

Microbiome research has grown significantly in the last decade, highlighting manifold implications of the microbiota to the host’s health. The gut microbiota is connected to the brain through several avenues that allow their interaction. Thus, recent studies have attemtpted to characterize these connections and enhance our understanding of the so called ‘gut-brain-axis’. Microglia, the central nervous system resident macrophages, are crucial for the proper development and maintenance of brain functions. As immune cells, they are in the spotlight for relaying signals between the microbiota and cells of the brain. In this review, we contemplate on interactions between the gut microbiota and microglia, and their influence on brain functions in health and disease.

In this personal view article, the impact of an auditory specialist, the barn owl, to our understanding of sensory processing, especially auditory processing, is discussed from the perspective of a long-lasting career. In times when research on model systems such as the mouse or the fruit fly, both generalists for most of the behaviors examined, celebrates big successes, one may ask what the work on animals occupying specialized niches, “specialists”, can contribute to advance our knowledge about sensory systems. A specialist in this context is an animal that occupies a certain ecological niche and shows corresponding adaptations in anatomy and physiology. This article presents a personal view on the impact of the work on such a specialist. In my article I shall focus on audition in the barn owl, a specialist for hunting by listening. I started my scientific career in 1979, working with houseflies, and have worked with barn owls since my time as a postdoc at the California Institute of Technology (“Caltech”, Pasadena, CA, USA) in 1985. My interest in specialists derived from my work as an ornithologist when I realized that adaptations like the long and curved bill of the curlew help animals to occupy certain ecological niches. I wanted to understand in a formal sense, and in comparison to engineering, how evolution shapes such specializations.