ABSTRACT
Research shows that across life, the incidence of mental illness is highest in the young. In the context of the COVID-19 pandemic, mental health issues of the young in particular have received global attention. The rostral anterior cingulate cortex (rACC) plays an important role in psychiatric disorders and chronic pain-psychiatric comorbidities. However, it remains unknown whether or how the afferent and efferent circuits of the rACC change with aging. In this study, we microinjected a retrograde tracer virus and an anterograde trans-monosynaptic virus into the rACC of young and middle-aged mice (both male and female), and systematically and quantitatively analyzed the whole-brain afferent and efferent connections of rACC at different ages and sexes. Notably, in young and middle-aged mice, afferents of the rACC belong to four groups of brain structures arising mainly from the amygdala [mainly basolateral amygdaloid nucleus (BLA)] and cerebral cortex (mainly orbital cortex), with a small part originating from the basal forebrain and thalamus. In contrast, efferents of the rACC belong to four groups of brain structures mainly projecting to the thalamus (mainly ventral anterior-lateral/ventromedial thalamic nucleus (VAL/VM)], with a very small part projecting to the amygdala, basal forebrain, and cerebral cortex. Compared with young mice, the BLA-rACC circuit in middle-aged mice (male and female) did not change significantly, while the rACC-VAL/VM circuit in middle-aged mice (male and female) decreased significantly. In conclusion, this study comprehensively analyzed the input-output neural projections of rACC in mice of different ages and sexes and provided preliminary evidence for further targeted research.
ABSTRACT
While IgM and IgG response to SARS-CoV-2 has been extensively studied, relatively little is known about secretory IgA (sIgA) response in respiratory mucosa. Here we report IgA response to the SARS-CoV-2 in sputum, throat swabs, and serum with nucleocapsid protein (NP) enzyme-linked immunosorbent assays (ELISA) in a cohort of 28 COVID-19 patients and 55 vaccine recipients. The assays showed sIgA in respiratory mucosa could be detected on the first day after illness onset (AIO), and the median conversion time for sIgA in sputum, throat swabs, and serum was 3, 4, and 10 days, respectively. The positive rates of sIgA first week AIO were 100% (24/28) and 85.7% (24/28) in sputum and throat swabs, respectively, and were both 100% during the mid-onset (2-3 weeks AIO). During the recovery period, sIgA positive rates in sputum and throat swabs gradually decreased from 60.7% (17/28) and 57.1% (16/28) 1 month AIO and the sIgA antibodies were all undetectable 6 months AIO. However, serum IgA positive rate was still 100% at 4 months and 53.6% (15/28) at 6 months. Throat swabs obtained from volunteers who received inactivated SARS-CoV-2 vaccines by intramuscular delivery all showed negative results in IgA ELISA. These findings will likely improve our understanding of respiratory mucosal immunity of this emerging disease and help in containing the pandemic and developing vaccines.