Biology subjects

Suh, M.

Publications and source records attributed to Suh, M..

5 recordsLinked to original sources

bioRxiv2026

Age-Related Increases in 40Hz Neural Synchrony Are Specific to Typical Development: A Cross-Sectional Study of Autism Spectrum Disorder

Background: The 40Hz auditory steady-state response (ASSR) is a measure of gamma-band neural synchrony sensitive to excitation-inhibition (E/I) balance. Disruptions to E/I balance have been implicated in autism spectrum disorder (ASD), making ASSR an efficient tool for investigating neural synchrony development in this population. Whether age-related differences in 40Hz ASSR are detectable across development in ASD remains understudied. Phelan-McDermid syndrome (PMS), a rare genetic disorder with a phenotype overlapping with autism, caused by SHANK3 disruption, provides a genetically defined model for further investigating E/I-related neural synchrony disruptions. Methods: We examined 40Hz inter-trial phase coherence (ITPC) as an index of neural synchrony across a wide age range (2-37 years) in 127 participants from four groups: TD (n=43), ASD without intellectual disability (w/o ID; n=37), ASD with intellectual disability (w/ID; n=24), and PMS (n=23). Given the distinct age and cognitive profiles of ASD subgroups in this sample, analyses were conducted in separate models: TD vs. ASD w/o ID across all ages, and TD vs. ASD w/ID vs. PMS restricted to participants under 18. Results: For the first time in a cross-sectional sample spanning a large age range, we show that 40Hz ITPC increases significantly with age in TD individuals, while this developmental trajectory is absent in ASD without intellectual disability. Among children and adolescents under 18, 40Hz ITPC did not differ across TD, ASD w/ID, and PMS, and IQ did not predict ITPC in clinical groups. A post-hoc analysis revealed higher ITPC in TD males than females, with no sex differences in ASD or PMS. Conclusions: We demonstrate that gamma-band ITPC trajectories diverge between TD and ASD, specifically in adulthood, with no such difference detectable in childhood. No significant group differences were found among TD, ASD w/ID, and PMS individuals under 18. These findings highlight the importance of age as a critical variable when measuring ASSR, and underscore the need for lifespan studies, particularly in genetically defined conditions such as PMS, to determine whether similar divergence emerges in adulthood.

neuroscience↗

bioRxiv2024

Lymphatic drainage of cerebrospinal fluid using lymph node seeker 64Cu-labeled Gram-negative bacterial extracellular vesicles PET

Cerebrospinal fluid (CSF) is drained into the systemic lymphatics via paravertebral lymph nodes. Superficial and deep cervical lymph nodes collect CSF in mice, but the exact and quantified routes are unknown. Recently, we simultaneously visualized cervical, sacral and iliac lymph nodes via serial imaging on the intrathecal [64Cu]Cu-albumin positron emission tomography. Paravertebral lymph nodes might act as sentinels to monitor the CSF, brain, and spinal cord. We used 64Cu-labeled Escherichia coli extracellular vesicles, outer membrane vesicles (OMVs), as lymph node seekers for intrathecal administration with an optimized volume/rate and quantified the differential amounts of various paravertebral lymph nodes along the axis of the brain and spinal cord in mice. The quantified results revealed 77.3% in superficial and deep cervical lymph nodes, 11.4% in abdominal/pelvic lymph nodes and 11.3% in sacral lymph nodes. Click-labeled [64Cu]Cu-OMVs were drained to reach and stop at the lymph nodes on serial quantification. The cervical lymph nodes drained most of the OMV-laden CSF, which is proportional to the surface areas of the brain (70%) and spinal cord in mice. We propose that all paravertebral lymph nodes monitor the segmental regions of the brain and spinal cord as immediate sentinel lymph nodes against the central nervous system.

neuroscience↗

bioRxiv2024

Intracortical injection of immune checkpoint inhibitor promotes monocyte/macrophage infiltration and restores microglial function and neuronal activity in an AD mouse model

Alzheimer's disease (AD) involves complex neuroimmune interactions. However, the role of immune checkpoint pathways in regulating the glial and neuronal functions of the AD brain remains unclear. This study aims to investigate how the brain-specific modulation of the PD-1/PD-L1 axis affects glial and neuronal function in an AD mouse model, which is characterized by the significant upregulation of microglial PD-1 and astrocytic PD-L1. A single intracortical administration of anti-PD-L1 antibody reshaped the glial microenvironment, which was accompanied by the restoration of impaired microglial process convergence. Astrocyte-specific Pd-l1 knockdown using the pSico system validated the essential role of astrocytic PD-L1 in enhancing microglial responses. Notably, the blockade of the PD-1/PD-L1 signaling pathway increased the microglial P2RY12 expression, a key marker of microglial homeostasis, which likely contributed to the restoration of neuronal hyperactivity. Collectively, these findings confirmed the potential of targeting the astrocyte-microglia PD-1/PD-L1 axis to mitigate AD pathology.

neuroscience↗

bioRxiv2023

Intrathecal Cu-albumin PET reveals age-related decline of cerebrospinal fluid (CSF)-lymphatic efflux

Age-related cognitive decline is associated with dysfunctional lymphatic efflux of cerebrospinal fluid (CSF) through meningeal lymphatic vessels. Intrathecal [64Cu]Cu-albumin positron emission tomography (PET) was applied in mice for the evaluation of lymphatic efflux of CSF and its age-related variation. [64Cu]Cu-albumin PET was done at multiple time points after intrathecal injection of [64Cu]Cu-albumin with the infusion speed of 700 nl/min in the adult and aged mice of 15-25 months old age. CSF clearance and paravertebral lymph nodes were quantified after injection and at later stationary phase. Representing perturbed state by 6 l (1/7 of CSF volume with twice the production rate for 9 minutes of intrathecal injection) and at the next day of stationary return of CSF dynamics in mice, CSF clearance half-time from the subarachnoid space was 93.4 {+/-} 19.7 in adult and 123.3 {+/-} 15.6 minutes in aged mice (p = 0.01). The % injected dose at 4, 6 and 24 hours were higher in aged mice than in the adult mice (p < 0.05) and the visualized paravertebral lymph node activity tended to be lower in the aged, which was different from [64Cu]Cu-NOTA or [64Cu]Cu-ESION PET. [64Cu]Cu-albumin PET enabled quantification of CSF-lymphatic efflux over all the levels of brain spinal cords and visualization with quantifiability of lymph node activity. [64Cu]Cu-albumin PET revealed an age-related decrease in CSF-lymphatic efflux due to less efflux from the subarachnoid space, especially at stationary phase in the aged mice.

neuroscience↗

bioRxiv2023

Spatial transcriptomic brain imaging reveals the effects of immunomodulation therapy upon specific regional brain cells in mouse dementia model

Increasing evidence of brain-immune crosstalk raises expectations for the efficacy of novel immunotherapies in Alzheimers disease (AD), but the lack of methods to understand brain tissues make it difficult to examine therapeutics. Here, we investigated the changes of spatial transcriptomic signatures and brain cell type using the 10x Genomics Visium platform in immune modulated AD models by various treatments. To proceed with an analysis suitable for a single spot-based transcriptomics, we first organized a workflow for segmentation of neuroanatomical regions, establishment of appropriate gene combinations, and comprehensive review of altered brain cell signatures. Ultimately, we investigated spatial transcriptomic changes following administration of immunomodulators, NK cell supplements and anti-CD4 antibody, that ameliorate behavior impairment, and designated brain cells and regions showing probable associations with behavior changes. We provided the customized analytic pipeline into an application named STquantool. Thus, we anticipate that our approach can help researchers to interpret real action of drug candidate by simultaneously investigating the dynamics of all transcripts for development of novel AD therapeutics.

neuroscience↗