Search

Background: Per- and polyfluoroalkyl substances (PFAS) are biopersistent, global pollutants. Although some in vitro and epidemiological studies have explored the neurotoxic potential of perfluorooctane sulfonate (PFOS), a prevalent PFAS congener, it is unknown how developmental PFOS exposure affects neuronal signaling, microglia development, and microglial-neuron communication. Objectives: We sought to determine the extent to which PFOS exposure disrupts brain health, neuronal activity, and microglia-neuron communication during development. In addition, although PFOS impairs humoral immunity, its impact on innate immune cells, including resident microglia, is unclear. As such, we investigated whether microglia are cellular targets of PFOS, and, if so, whether disrupted microglial development or function could contribute to or is influenced by PFOS-induced neural dysfunction. Methods: Zebrafish were chronically exposed to either a control solution [0.1% dimethyl sulfoxide (DMSO)], 7 [micro]M PFOS, 14 [micro]M PFOS, 28 [micro]M PFOS, or 64 [micro]M perfluorooctanoic acid (PFOA). We used in vivo imaging and gene expression analysis to assess microglial populations in the developing brain and to determine shifts in the microglia state. We functionally challenged microglia state using a brain injury model and, to assess the neuronal signaling environment, performed functional neuroimaging experiments using the photoconvertible calcium indicator calcium-modulated photoactivatable ratiometric integrator (CaMPARI). These studies were paired with optogenetic manipulations of neurons and microglia, an untargeted metabolome-wide association study (MWAS), and behavioral assays. Results: Developmental PFOS exposure resulted in a shift away from the homeostatic microglia state, as determined by functional and morphological differences in exposed larvae, as well as up-regulation of the microglia activation gene p2ry12. PFOS-induced effects on microglia state exacerbated microglia responses to brain injury in the absence of increased cell death or inflammation. PFOS exposure also heightened neural activity, and optogenetic silencing of neurons or microglia independently was sufficient to normalize microglial responses to injury. An untargeted MWAS of larval brains revealed PFOS-exposed larvae had neurochemical signatures of excitatory-inhibitory imbalance. Behaviorally, PFOS-exposed larvae also exhibited anxiety-like thigmotaxis. To test whether the neuronal and microglial phenotypes were specific to PFOS, we exposed embryos to PFOA, a known immunotoxic PFAS. PFOA did not alter thigmotaxis, neuronal activity, or microglial responses, further supporting a role for neuronal activity as a critical modifier of microglial function following PFOS exposure. Discussion: Together, this study provides, to our knowledge, the first detailed account of the effects of PFOS exposure on neural cell types in the developing brain in vivo and adds neuronal hyperactivity as an important end point to assess when studying the impact of toxicant exposures on microglia function. https://doi.org/10.1289/EHP12861, Introduction Pollution poses a global threat to environmental, ecologic, and economic health and stability. As international geologic committees consider whether we have now entered the Anthropocene Age, it is of [...]

Vertebrate dentitions are often collapsed into a few discrete categories, obscuring both potentially important functional differences between them and insight into their evolution. The terms homodonty and heterodonty typically conflate tooth morphology with tooth function, and require context-dependent subcategories to take on any specific meaning. Qualifiers like incipient, transient, or phylogenetic homodonty attempt to provide a more rigorous definition but instead highlight the difficulties in categorizing dentitions. To address these issues, we recently proposed a method for quantifying the function of dental batteries based on the estimated stress of each tooth (inferred using surface area) standardized for jaw out-lever (inferred using tooth position). This method reveals a homodonty–heterodonty functional continuum where small and large teeth work together to transmit forces to a prey item. Morphological homodonty or heterodonty refers to morphology, whereas functional homodonty or heterodonty refers to transmission of stress. In this study, we use Halichoeres wrasses to explore how a functional continuum can be used in phylogenetic analyses by generating two continuous metrics from the functional homodonty–heterodonty continuum. Here we show that functionally heterodont teeth have evolved at least 3 times in Halichoeres wrasses. There are more functionally heterodont teeth on upper jaws than on lower jaws, but functionally heterodont teeth on the lower jaws bear significantly more stress. These nuances, which have functional consequences, would be missed by binning entire dentitions into discrete categories. This analysis points out areas worth taking a closer look at from a mechanical and developmental point of view with respect to the distribution and type of heterodonty seen in different jaws and different areas of jaws. These data, on a small group of wrasses, suggest continuous dental variables can be a rich source of insight into the evolution of fish feeding mechanisms across a wider variety of species. [ABSTRACT FROM AUTHOR]

Locomotion in water and on land impose dramatically different demands, yet many animals successfully move in both environments. Most turtle species perform both aquatic and terrestrial locomotion but vary in how they use their limbs. Freshwater turtles use anteroposterior movements of the limbs during walking and swimming with contralateral fore- and hindlimbs moving in synchrony. In contrast, sea turtles swim primarily with "powerstroke" movements, characterized by synchronous forelimb motions while the hindlimbs act as rudders. High-speed video has been used to study powerstroking, but pectoral girdle movements and long-axis rotation (LAR) of the humerus are likely both key components to turtle locomotor function and cannot be quantified from external video. Here, we used XROMM to measure pectoral girdle and humeral movements in a sea turtle (loggerhead, Caretta caretta) compared to the freshwater river cooter (Pseudemys concinna) during terrestrial and aquatic locomotion. The largest difference among species was in yaw of the pectoral girdle during swimming, with loggerheads showing almost no yaw during powerstroking whereas pectoral girdle yaw in the cooter during rowing was over 30°. The magnitude of humeral LAR was greatest during loggerhead powerstroking and the temporal pattern of supination and pronation was opposite from that of cooters. We hypothesize that these kinematic differences are driven by differences in how the limbs are used to power propulsion. Rotations at the glenoid drive the overall patterns of movement in freshwater turtles, whereas glenohumeral LAR in loggerheads is used to direct the position and orientation of the elbow, which is the joint that determines the orientation of the thrust-generating structure (the flipper) in loggerheads., (© 2024 Wiley Periodicals LLC.)