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Background: It has long been known that thyroid disease can lead to changes in energy metabolism, thermoregulation, and anxiety behavior. While these actions have been partially attributed to thyroid hormone (TH) receptor α1 (TRα1) action in the brain, the precise neuroanatomical substrates have remain elusive. Methods: We used PET-CT scans to identify brain regions affected by TH. We then inhibited TRα1 signaling specifically in the most affected region, the zona incerta (ZI), a still mysterious region previously implicated in thermogenesis and anxiety. To this end, we used an adeno-associated virus (AAV) expressing a dominant-negative TRα1R384C in wild-type mice and phenotyped the animals. Finally, we used tyrosine hydroxylase-Cre mice to test specifically the contribution of ZI dopaminergic neurons. Results: Our data showed that AAV-mediated inhibition of TRα1 signaling in the ZI lead to increased energy expenditure at thermoneutrality, while body temperature regulation remained unaffected. Moreover, circulating glucocorticoid levels were increased, and a mild habituation problem was observed in the open field test. No effects were observed when TRα1 signaling was selectively inhibited in dopaminergic neurons. Conclusions: Our findings suggest that altered TH signaling in the ZI is not involved in body temperature regulation but can affect basal metabolism and modulates stress responses. [ABSTRACT FROM AUTHOR]

Transcranial alternating current stimulation (tACS) is an emerging non-invasive tool for modulating brain oscillations. There is evidence that weak oscillatory electrical stimulation during sleep can entrain cortical slow oscillations to improve the memory consolidation in rodents and humans. Using a novel method and a custom built stimulation device, automatic stimulation of slow oscillations in-phase with the endogenous activity in a real-time closed-loop setup is possible. Preliminary data from neuroplasticity experiments show a high detection performance of the proposed method, electrical measurements demonstrate the outstanding quality of the presented stimulation device.

In this study, we have investigated the contribution of oligodendrocytic connexin47 (Cx47) and astrocytic Cx30 to panglial gap junctional networks as well as myelin maintenance and function by deletion of both connexin coding DNAs in mice. Biocytin injections revealed complete disruption of oligodendrocyte-to-astrocyte coupling in the white matter of 10- to 15-d-old Cx30/Cx47 double-deficient mice, while oligodendrocyte-to-oligodendrocyte coupling was maintained. There were no quantitative differences regarding cellular networks in acute brain slices obtained from Cx30/Cx47 double-null mice and control littermates, probably caused by the upregulation of oligodendrocytic Cx32 in Cx30/Cx47 double-deficient mice. We observed early onset myelin pathology, and ∼40% of Cx30/Cx47 doubledeficient animals died within 42 to 90 d after birth, accompanied by severe motor impairments. Histological and ultrastructural analyses revealed severe vacuolization and myelination defects in all white matter tracts of the CNS. Furthermore, Cx30/Cx47 double-deficient mice exhibited a decreased number of oligodendrocytes, severe astrogliosis, and microglial activation in white matter tracts. Although less affected concerning motor impairment, surviving double-knock-out (KO) mice showed behavioral alterations in the open field and in the rotarod task. Vacuole formation and thinner myelin sheaths were evident also with adult surviving double-KO mice. Since interastrocytic coupling due to Cx43 expression and interoligodendrocytic coupling because of Cx32 expression are still maintained, Cx30/Cx47 double-deficient mice demonstrate the functional role of both connexins for interastrocytic, interoligodendrocytic, and panglial coupling, and show that both connexins are required for maintenance of myelin. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) can damage cerebral small vessels and cause neurological symptoms. Here we describe structural changes in cerebral small vessels of patients with COVID-19 and elucidate potential mechanisms underlying the vascular pathology. In brains of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected individuals and animal models, we found an increased number of empty basement membrane tubes, so-called string vessels representing remnants of lost capillaries. We obtained evidence that brain endothelial cells are infected and that the main protease of SARS-CoV-2 (M pro ) cleaves NEMO, the essential modulator of nuclear factor-κB. By ablating NEMO, M pro induces the death of human brain endothelial cells and the occurrence of string vessels in mice. Deletion of receptor-interacting protein kinase (RIPK) 3, a mediator of regulated cell death, blocks the vessel rarefaction and disruption of the blood-brain barrier due to NEMO ablation. Importantly, a pharmacological inhibitor of RIPK signaling prevented the M pro -induced microvascular pathology. Our data suggest RIPK as a potential therapeutic target to treat the neuropathology of COVID-19., (© 2021. The Author(s).)