LIF signaling regulates outer radial glial to interneuron fate during human cortical development.

Radial glial (RG) development is essential for cerebral cortex growth and organization. In humans, the outer radial glia (oRG) subtype is expanded and gives rise to diverse neurons and glia. However, the mechanisms regulating oRG differentiation are unclear. oRG cells express leukemia-inhibitory factor (LIF) receptors during neurogenesis, and consistent with a role in stem cell self-renewal, LIF perturbation impacts oRG proliferation in cortical tissue and organoids. Surprisingly, LIF treatment also increases the production of inhibitory interneurons (INs) in cortical cultures. Comparative transcriptomic analysis identifies that the enhanced IN population resembles INs produced in the caudal ganglionic eminence. To evaluate whether INs could arise from oRGs, we isolated primary oRG cells and cultured them with LIF. We observed the production of INs from oRG cells and an increase in IN abundance following LIF treatment. Our observations suggest that LIF signaling regulates the capacity of oRG cells to generate INs.

Oxygen supply limits the chronic heat tolerance of locusts during the first instar only.

Although scientists know that overheating kills many organisms, they do not agree on the mechanism. According to one theory, referred to as oxygen- and capacity-limitation of thermal tolerance, overheating occurs when a warming organism's demand for oxygen exceeds its supply, reducing the organism's supply of ATP. This model predicts that an organism's heat tolerance should decrease under hypoxia, yet most terrestrial organisms tolerate the same amount of warming across a wide range of oxygen concentrations. This point is especially true for adult insects, who deliver oxygen through highly efficient respiratory systems. However, oxygen limitation at high temperatures may be more common during immature life stages, which have less developed respiratory systems. To test this hypothesis, we measured the effects of heat and hypoxia on the survival of South American locusts (Schistocerca cancellata) throughout development and during specific instars. We demonstrate that the heat tolerance of locusts depends on oxygen supply during the first instar but not during later instars. This finding provides further support for the idea that oxygen limitation of thermal tolerance depends on respiratory performance, especially during immature life stages.

Chronic unpredictable intermittent restraint stress disrupts spatial memory in male, but not female rats.

Chronic stress leads to sex-dependent outcomes on spatial memory by producing deficits in males, but not in females. Recently it was reported that compared to daily restraint, intermittent restraint (IR) produced more robust stress and anxiety responses in male rats. Whether IR would be sufficiently robust to impair hippocampal-dependent spatial memory in both male and female rats was investigated. IR involved mixing restraint with non-restraint days over weeks before assessing spatial memory and anxiety profile on the radial arm water maze, object placement, novel object recognition, Y-maze, open field and novelty suppressed feeding. Experiments 1 and 2 used Sprague-Dawley male rats only and determined that IR for 6 h/d (IR6), but not 2 h/d, impaired spatial memory and that task order was important. In experiment 3, IR6 was extended for 6wks before spatial memory testing commenced using both sexes. Unexpectedly, an extended IR6 paradigm failed to impair spatial memory in either sex, suggesting that by 6wks IR6 may have become predictable. In experiment 4, an unpredictable IR (UIR) paradigm was implemented, in which restraint duration (30 or 60-min) combined with orbital shaking, time of day, and the days off from UIR were varied. UIR impaired spatial memory in males, but not in females. Together with other reports, these findings support the interpretation that chronic stress negatively impairs hippocampal-dependent function in males, but not in females. We interpret these findings to show that females are more resilient to chronic stress than are males as it pertains to spatial ability.