TY - JOUR T1 - ACE2 expression in rat brain: implications for COVID-19 associated neurological manifestations JF - bioRxiv DO - 10.1101/2021.05.01.442293 SP - 2021.05.01.442293 AU - Vito S Hernández AU - Mario A Zetter AU - Enrique C. Guerra AU - Ileana Hernández-Araiza AU - Nikita Karuzin AU - Oscar R. Hernández-Pérez AU - Lee E Eiden AU - Limei Zhang Y1 - 2021/01/01 UR - http://biorxiv.org/content/early/2021/05/03/2021.05.01.442293.abstract N2 - We examined cell type-specific expression and distribution of rat brain angiotensin converting enzyme 2 (ACE2), the receptor for SARS-CoV-2, in rodent brain. ACE2 is ubiquitously present in brain vasculature, with the highest density of ACE2 expressing capillaries found in the olfactory bulb, the hypothalamic paraventricular, supraoptic and mammillary nuclei, the midbrain substantia nigra and ventral tegmental area, and the hindbrain pontine nucleus, pre-Bötzinger complex, and nucleus of tractus solitarius. ACE2 was expressed in astrocytes and astrocytic foot processes, pericytes and endothelial cells, key components of the blood-brain-barrier. We found discrete neuronal groups immunopositive for ACE2 in brainstem respiratory rhythm generating centers including the pontine nucleus, the parafascicular/retrotrapezoid nucleus, the parabrachial nucleus, the Bötzinger and pre-Bötzinger complex and the nucleus of tractus solitarius; in arousal-related pontine reticular nucleus and in gigantocellular reticular nuclei; in brainstem aminergic nuclei, including substantia nigra, ventral tegmental area, dorsal raphe, and locus coeruleus; in the epithalamic habenula, hypothalamic paraventricular and suprammamillary nuclei; and in the hippocampus. Identification of ACE2-expressing neurons in rat brain within well-established functional circuits facilitates prediction of possible neurological manifestations of brain ACE2 dysregulation during and after COVID-19 infection.HighlightsACE2 is present in astrocytes, pericytes, and endothelia of the blood brain barrier.Neuronal ACE2 expression is shown in discrete nuclei through the brain.Brainstem breathing, arousal-related, hypothalamic and limbic nuclei express ACE2.ACE2 is expressed in circuits potentially involved in COVID-19 pathophysiology.Competing Interest StatementThe authors have declared no competing interest. ER -