Biology subjects

Anderson, E. D.

Publications and source records attributed to Anderson, E. D..

5 recordsLinked to original sources

bioRxiv2025

Microglia modulate concussion biomarkers and cognitive recovery in male mice

There is a critical unmet need for concussion biomarkers that predict cognitive recovery. Existing TBI biomarkers largely capture acute cellular damage rather than the multicellular repair processes that determine long-term outcome, and whether microglia causally shape divergent trajectories remains unclear. Here, we used PLX5622 to deplete microglia and other CSF1R-dependent myeloid cells in a male mouse model comparing concussion alone to concussion preconditioned by prior subconcussive impacts. Microglial depletion had no effect on cognitive outcome after concussion alone, but introduced a significant novel object recognition deficit specifically when concussion was preconditioned, revealing a history-dependent role for microglia in recovery. To identify the molecular substrates of this divergence, we profiled brain-derived GluA1/2+ extracellular vesicle (EV) miRNAs and single-nuclei transcriptomes from the injured brain. Diagnostic and injury-history EV miRNA biomarkers discriminated between concussion subtypes in microglia-intact animals but lost this discriminative power after depletion, indicating that these neuron-enriched biomarkers are influenced by microglia-dependent biology rather than injury alone. snRNA-seq further revealed that microglial depletion selectively induced transcriptional programs related to oligodendrocyte maturation after unconditioned concussion, a candidate substrate for this microglia-dependence. Finally, we identified a serum EV miRNA panel that estimated cognitive recovery across injury conditions. Together, these findings identify a history-dependent role for microglia in concussion outcome and characterize brain-derived EVs as a potentially promising tool for surveilling the neuroinflammatory processes influencing recovery.

bioengineering↗

bioRxiv2025

Subconcussive preconditioning prevents microglial morphology changes and improves cognitive outcomes in mice

Subconcussive impacts are highly prevalent in contact sports and are thought to increase concussion risk. However, the specific conditions under which these subconcussive impacts influence concussion outcomes are uncertain, limiting our understanding of the mechanisms behind repetitive head trauma. Given that subconcussive impacts elicit a microglial response, and microglial morphology offers insight into function, we examined how subconcussive preconditioning affects microglial morphology and cognitive outcome after concussion. To investigate this question, we developed and validated a scalable, closed-head controlled cortical impact model. Using this approach, we found that although concussion elicited features of hypersurveillant microglia at 1 day post-injury, they resolve by 9 days post-injury, and subconcussive impacts only produced microglial changes at 9 days post-injury. When subconcussive impacts preceded a concussive impact (i.e., preconditioned concussion) no changes in microglial morphology appeared at either 1 or 9 days after injury. Interestingly, subconcussive preconditioning eliminated concussion-associated cognitive deficits in novel object recognition and this cognitive protection was time dependent: preconditioning impacts were only protective if delivered within 2 minutes of concussion, and had no effect if delivered over a 48-hour window. These results suggest that some types of subconcussive impacts may offer protection against subsequent concussion and mitigate changes in microglial morphology. Understanding this timing window could inform strategies for minimizing cognitive impairments in athletes exposed to repetitive head trauma.

bioengineering↗

bioRxiv2023

Human Intelligence and the Connectome are Driven by Structural Brain Network Control

Research in network neuroscience demonstrates that human intelligence is shaped by the structural brain connectome, which enables a globally coordinated and dynamic architecture for general intelligence. Building on this perspective, the network neuroscience theory proposes that intelligence arises from system-wide network dynamics and the capacity to flexibly transition between network states. According to this view, network flexibility is made possible by network controllers that move the system into specific network states, enabling solutions to familiar problems by accessing nearby, easy-to-reach network states and adapting to novel situations by engaging distant, difficult-to-reach network states. Although this framework predicts that general intelligence depends on network controllability, the specific cortical regions that serve as network controllers and the nature of their control operations remain to be established. We therefore conducted a comprehensive investigation of the relationship between regional measures of network controllability and general intelligence within a sample of 275 healthy young adults using structural and diffusion-weighted MRI data. Our findings revealed significant associations between intelligence and network controllers located within the frontal, temporal and parietal cortex. Furthermore, we discovered that these controllers collectively enable access to both easy- and difficult-to-reach network states, aligning with the predictions made by the network neuroscience framework. Additionally, our research demonstrated that the identified network controllers are primarily localized within the left hemisphere and do not reside within regions or connections that possess the highest capacity for structural control in general. This discovery suggests that the identified regions may facilitate specialized control operations and motivates further exploration of the network topology and dynamics underlying intelligence in the human brain. SummaryThis study examines the relationship between regional measures of network controllability and general intelligence within a sample of 275 healthy young adults using structural and diffusion-weighted MRI data. We report that individual differences in general intelligence are associated average and modal controllability in specific left-hemisphere cortical regions, and further show that controller regions associated with intelligence are distinct from regions with the highest, centrality, controllability, or communication. These findings reveal a significant structural role for individual regions in controlling the trajectory of the connectome, advancing our understanding of the nature and mechanisms of network controllability in general intelligence.

neuroscience↗

bioRxiv2018

Prolonged culture of primary human keratinocytes isolated from suction blisters

Keratinocytes are the most abundant cell type in the epidermis. They prevent desiccation and provide immunological and barrier defense against potential pathogens such as Staphylococcus aureus and Candida albicans. The study of this first line of immune defense is hindered by invasive isolation methods and insufficient techniques for long-term passage of primary keratinocytes in vitro. Primary keratinocytes have been successfully isolated from blister roofs induced by negative pressure, which separates the epidermis from the dermis in vivo in human subjects. This method allows collection of pure epidermal cells without dermal contamination in a minimally invasive manner. However, the isolated keratinocytes differentiate and senesce when cultured in vitro beyond five passages. Here, we present evidence that the Rho kinase (ROCK) inhibitor Y-27632 can be used to effectively increase the proliferative capabilities of keratinocytes isolated using the suction blister method, similar to what has been previously reported for primary keratinocytes isolated using alternative methods. We show that the increase in passage number is directly correlated to delayed differentiation, and that cells passaged long term with the inhibitor retain their ability to stratify in organotypic raft cultures and respond to cytokine treatment; additionally, the late passage cells have a heterogeneous mix of differentiated and non-differentiated cells which may be predicted by a ratio of select differentiation markers. The described method presents a minimally invasive procedure for keratinocyte isolation and prolonged culture that allows analysis of keratinocyte function in both healthy volunteers and patients with dermatologic diseases.

cell biology↗

bioRxiv2017

Magnetic Entropy as a Gating Mechanism for Magnetogenetic Ion Channels

Magnetically sensitive ion channels would allow researchers to better study how specific brain cells affect behavior in freely moving animals; however, recent reports of \"magnetogenetic\" ion channels have been questioned because known biophysical mechanisms cannot explain experimental observations. Here we show that magnetic fields can produce a change in the magnetic entropy of biogenic nanoparticles, which in turn may generate sufficient heat to gate temperature-sensitive ion channels. This magnetocaloric effect provides a rational approach for developing future magnetogenetic channels.

neuroscience↗