RESUMO
BACKGROUND: The nucleus incertus (NI) was originally described by Streeter in 1903, as a midline region in the floor of the fourth ventricle of the human brain with an 'unknown' function. More than a century later, the neuroanatomy of the NI has been described in lower vertebrates, but not in humans. Therefore, we examined the neurochemical anatomy of the human NI using markers, including the neuropeptide, relaxin-3 (RLN3), and began to explore the distribution of the NI-related RLN3 innervation of the hippocampus. METHODS: Histochemical staining of serial, coronal sections of control human postmortem pons was conducted to reveal the presence of the NI by detection of immunoreactivity (IR) for the neuronal markers, microtubule-associated protein-2 (MAP2), glutamic acid dehydrogenase (GAD)-65/67 and corticotrophin-releasing hormone receptor 1 (CRHR1), and RLN3, which is highly expressed in NI neurons in diverse species. RLN3 and vesicular GABA transporter 1 (vGAT1) mRNA were detected by fluorescent in situ hybridization. Pons sections containing the NI from an AD case were immunostained for phosphorylated-tau, to explore potential relevance to neurodegenerative diseases. Lastly, sections of the human hippocampus were stained to detect RLN3-IR and somatostatin (SST)-IR. RESULTS: In the dorsal, anterior-medial region of the human pons, neurons containing RLN3- and MAP2-IR, and RLN3/vGAT1 mRNA-positive neurons were observed in an anatomical pattern consistent with that of the NI in other species. GAD65/67- and CRHR1-immunopositive neurons were also detected within this area. Furthermore, RLN3- and AT8-IR were co-localized within NI neurons of an AD subject. Lastly, RLN3-IR was detected in neurons within the CA1, CA2, CA3 and DG areas of the hippocampus, in the absence of RLN3 mRNA. In the DG, RLN3- and SST-IR were co-localized in a small population of neurons. CONCLUSIONS: Aspects of the anatomy of the human NI are shared across species, including a population of stress-responsive, RLN3-expressing neurons and a RLN3 innervation of the hippocampus. Accumulation of phosphorylated-tau in the NI suggests its possible involvement in AD pathology. Further characterization of the neurochemistry of the human NI will increase our understanding of its functional role in health and disease.
Assuntos
Ponte , Humanos , Ponte/metabolismo , Masculino , Hipocampo/química , Hipocampo/metabolismo , Feminino , Relaxina/metabolismo , Relaxina/genética , Idoso , Neurônios/química , Memória/fisiologia , Proteínas Associadas aos Microtúbulos/metabolismo , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Glutamato Descarboxilase/metabolismo , Glutamato Descarboxilase/genética , Receptores de Hormônio Liberador da CorticotropinaRESUMO
Bats (order Chiroptera) are some of the most abundant mammals on earth and their species ecology strongly influences zoonotic potential. While substantial research has been conducted on bat-associated viruses, particularly on those that can cause disease in humans and/or livestock, globally, limited research has focused on endemic bats in the USA. The southwest region of the US is of particular interest because of its high diversity of bat species. We identified 39 single-stranded DNA virus genomes in the feces of Mexican free-tailed bats (Tadarida brasiliensis) sampled in the Rucker Canyon (Chiricahua Mountains) of southeast Arizona (USA). Twenty-eight of these belong to the virus families Circoviridae (n = 6), Genomoviridae (n = 17), and Microviridae (n = 5). Eleven viruses cluster with other unclassified cressdnaviruses. Most of the viruses identified represent new species. Further research on identification of novel bat-associated cressdnaviruses and microviruses is needed to provide greater insights regarding their co-evolution and ecology relative to bats.