Developmental Lead Exposure in Rats Causes Sex-Dependent Changes in Neurobiological and Anxiety-Like Behaviors that Are Improved by Taurine Co-treatment.

Lead (Pb2+) is a developmental neurotoxicant that causes alterations in the brain's excitation-to-inhibition (E/I) balance by disrupting the development of the GABAergic systems. These GABAergic disruptions have persistent neurobiological and neurobehavioral structure-function relationships that can be examined using animal models of Pb2+ exposure. Further, taurine, a GABA-AR agonist, has been shown to offer neuroprotection against neurodevelopmental Pb2+ exposure and senescence. The present study evaluated the effects of Pb2+ exposure (i.e., at 150 ppm and 1,000 ppm doses) on Long Evans hooded rats during the perinatal period of development on locomotor activity in the open field (OF) and anxiety-like behaviors in the elevated plus maze (EPM). This was followed by an examination of brain mass using an encephalization quotient (EQ) and isotropic fractionation (ITF) of total cells and the number of neurons and non-neuronal cells in the prefrontal cortex, hippocampus, and diencephalon. The results suggest that neurodevelopmental Pb2+ exposure caused persistent anxiety-like behaviors in both the OF and EPM with associated changes in EQ, but not ITF-determined cell density. Further, taurine treatment was observed to compensate for Pb2+ exposure in the behavioral assessments although precise neurobiological mechanisms remain unknown. Thus, more work is required to evaluate the role of taurine and other anxiolytic compounds in the alleviation of neurotoxicant-induced neurobehavioral syndromes and their associated neurobiological correlates.

The nervous system during COVID-19: Caught in the crossfire.

SARS-CoV-2, the virus that causes coronavirus disease (COVID)-19, has become a persistent global health threat. Individuals who are symptomatic for COVID-19 frequently exhibit respiratory illness, which is often accompanied by neurological symptoms of anosmia and fatigue. Mounting clinical data also indicate that many COVID-19 patients display long-term neurological disorders postinfection such as cognitive decline, which emphasizes the need to further elucidate the effects of COVID-19 on the central nervous system. In this review article, we summarize an emerging body of literature describing the impact of SARS-CoV-2 infection on central nervous system (CNS) health and highlight important areas of future investigation.

Neurobiological effects of a probiotic-supplemented diet in chronically stressed male Long-Evans rats: Evidence of enhanced resilience.

Probiotics that regulate the microbiome-gut-brain axis and provide mental health benefits to the host are referred to as psychobiotics. Preclinical studies have demonstrated psychobiotic effects on early life stress-induced anxiety- and depression-related behavior in rodents; however, the specific mechanisms remain ill-defined. In the current study, we investigated the effects of probiotic supplementation on neurobiological responses to chronic stress in adult male Long-Evans rats. Twenty-four rats were randomly assigned to probiotic (PB) or vehicle control (VEH) groups, then to either chronic unpredictable stress (CUS) or no-stress control (CON) conditions within each group (n = 6/subgroup). We hypothesized that PB supplementation would reduce markers of anxiety and enhance emotional resilience, especially in the CUS animals. In the cognitive uncertainty task, a nonsignificant trend was observed indicating that the PB-supplemented animals spent more time oriented toward the food reward than VEH animals. In the open-field task, CUS-PB animals spent more time in the center of the arena than CUS-VEH animals, an effect not observed between the two CON groups. In the swim task, the PB animals, regardless of stress assignment, exhibited increased floating, suggesting a conserved response in a challenging context. Focusing on the endocrine measures, higher dehydroepiandrosterone (DHEA)-to-corticosterone fecal metabolite ratios, a correlate of emotional resilience, were observed in PB animals. Further, PB animals exhibited reduced microglia immunoreactivity in the basolateral amygdala, possibly indicating a neuroprotective effect of PB supplements in this rodent model. These results provide evidence that PB supplementation interacts with stress exposure to influence adaptive responses associated with endocrine, neural, and behavioral indices of anxiety.

Cytoarchitectural characteristics associated with cognitive flexibility in raccoons.

With rates of psychiatric illnesses such as depression continuing to rise, additional preclinical models are needed to facilitate translational neuroscience research. In the current study, the raccoon (Procyon lotor) was investigated due to its similarities with primate brains, including comparable proportional neuronal densities, cortical magnification of the forepaw area, and cortical gyrification. Specifically, we report on the cytoarchitectural characteristics of raccoons profiled as high, intermediate, or low solvers in a multiaccess problem-solving task. Isotropic fractionation indicated that high-solvers had significantly more cells in the hippocampus (HC) than the other solving groups; further, a nonsignificant trend suggested that this increase in cell profile density was due to increased nonneuronal (e.g., glial) cells. Group differences were not observed in the cellular density of the somatosensory cortex. Thionin-based staining confirmed the presence of von Economo neurons (VENs) in the frontoinsular cortex, although no impact of solving ability on VEN cell profile density levels was observed. Elongated fusiform cells were quantified in the HC dentate gyrus where high-solvers were observed to have higher levels of this cell type than the other solving groups. In sum, the current findings suggest that varying cytoarchitectural phenotypes contribute to cognitive flexibility. Additional research is necessary to determine the translational value of cytoarchitectural distribution patterns on adaptive behavioral outcomes associated with cognitive performance and mental health.

IgG Antibodies against SARS-CoV-2 Correlate with Days from Symptom Onset, Viral Load and IL-10.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in a pandemic of the respiratory disease coronavirus disease 2019 (COVID-19). Antibody testing is essential to identify persons exposed to the virus and potentially in predicting disease immunity. 183 COVID-19 patients (68 of whom required mechanical ventilation) and 41 controls were tested for plasma IgG, IgA and IgM against the SARS-CoV-2 S1, S2, receptor binding domain (RBD) and N proteins using the MILLIPLEX® SARS-CoV-2 Antigen Panel. Plasma cytokines were concurrently measured using the MILLIPLEX® MAP Human Cytokine/Chemokine/Growth Factor Panel A. As expected the 183 COVID-19 positive patients had high levels of IgG, IgA and IgM anti-SARS-CoV-2 antibodies against each of the viral proteins. Sensitivity of anti-S1 IgG increased from 60% to 93% one week after symptom onset. S1-IgG and S1-IgA had specificities of 98% compared to the 41 COVID-19 negative patients. The 68 ventilated COVID-19 positive patients had higher antibody levels than the 115 COVID-19 positive patients who were not ventilated. IgG antibody levels against S1 protein had the strongest positive correlation to days from symptom onset. There were no statistically significant differences in IgG, IgA and IgM antibodies against S1 based on age. We found that patients with the highest levels of anti-SARS-CoV-2 antibodies had the lowest viral load in the nasopharynx. Finally there was a correlation of high plasma IL-10 with low anti-SARS-CoV-2 antibodies. Anti-SARS-CoV-2 antibody levels, as measured by a novel antigen panel, increased within days after symptom onset, achieving > 90% sensitivity and specificity within one week, and were highest in patients who required mechanical ventilation. Antibody levels were inversely associated with viral load but did not differ as a function of age. The correlation of high IL-10 with low antibody response suggests a potentially suppressive role of this cytokine in the humoral immune response in COVID-19.