MacKenzie Bolen

All Publications

• C1q-dependent clearance of alpha-synuclein allows macrophages to transiently limit enteric synucleinopathy in male mice. Nature communications Mackie, P. M., Koshy, J. M., Bhogade, M. H., Hammoor, T., Hachmeister, W., Lloyd, G. M., Paterno, G., Bolen, M. L., Merchak, A., Gamez-Tansey, M., Giasson, B. I., Khoshbouei, H. 2026

  Abstract

  Deposition of misfolded α-synuclein (αsyn) in the enteric nervous system (ENS) is found in multiple neurodegenerative diseases. It is hypothesized that ENS synucleinopathy contributes to both the pathogenesis and non-motor morbidity in Parkinson's Disease (PD), but the cellular and molecular mechanisms that shape enteric histopathology and dysfunction are poorly understood. Here, we employ a fibrillar injection model of enteric synucleinopathy in male mice and demonstrate that ENS-resident macrophages, which play a critical role in maintaining ENS homeostasis, initially respond to enteric neuronal αsyn pathology by upregulating machinery for complement-mediated engulfment. Pharmacologic depletion of ENS-macrophages or genetic deletion of C1q enhanced enteric neuropathology. Conversely, C1q deletion ameliorated gut dysfunction, indicating that complement partially mediates αsyn-induced gut dysfunction. However, this C1q-dependent clearance mechanism diminished over time and its failure temporally correlated with the further increase in ENS pathology. These findings highlight the importance of enteric neuron-macrophage interactions in removing toxic protein aggregates that putatively shape the gastrointestinal manifestations of PD.

  View details for DOI 10.1038/s41467-026-68641-8

  View details for PubMedID 41554750

• Spatial single-cell multiomics reveals peripheral immune dysfunction in Parkinson's and inflammatory bowel disease. NPJ Parkinson's disease Bolen, M. L., Buendia, M., Shi, J., Staley, H., Kachergus, J. M., Efron, P. A., Park, G., Nagpal, R., Alvarez, S. D., Xue, Q. S., McFarland, N. R., Zimmermann, E. M., Forsmark, C. E., Menees, K. B., Salas, A., Aubrey Thompson, E., Tansey, M. G. 2026

  Abstract

  Parkinson's disease (PD) is the fastest-growing neurodegenerative disease in the world1. Gastrointestinal (GI) dysfunction can occur decades before motor impairments and in up to 80% of individuals living with PD2-4. We investigated peripheral relationships that may underlie mechanisms along the gut-blood axis that contribute to PD progression. Single-cell multiomic spatial molecular imaging (SMI) of colonic tissue localized and identified inflammatory injury within epithelial cells that appear to be associated with iron mishandling in both inflammatory bowel disease (IBD) and PD biosamples. We found that both the single-cell SMI of RNA and protein revealed parallel cross-modal dysregulation in the gut epithelium, in both IBD and PD biosamples. These data are accompanied by plasma (PD) and stool (IBD) protein depletion of CCL22. Our findings suggest iron mishandling along the gut barrier likely contributes to systemic inflammation, which may be one catalyst that primes circulating immune cells to body-first PD progression.

  View details for DOI 10.1038/s41531-025-01199-2

  View details for PubMedID 41545356

• Iron mishandling in the brain and periphery in Parkinson's disease. NPJ Parkinson's disease Bolen, M. L., Menees, K. B., Dupreez, A. C., Tansey, M. G. 2025; 11 (1): 246

  Abstract

  The heterogeneous prodromal phase of Parkinson's disease (PD) has made identifying catalysts that drive disease progression critical for effective development of disease-modifying therapies. Recently, the role of gastrointestinal dysfunction in inflammation that drives neurodegenerative risk has gained attention as a target for intervention. However, to date, there have been no clear internal or environmental catalysts identified in the gut that drive risk for PD. Here, we review the literature on iron dysregulation in the brain, blood, and gut in PD and propose that iron dysregulation outside the brain is an important catalyst that may represent a prodromal mechanistic link in gut-first PD.

  View details for DOI 10.1038/s41531-025-01089-7

  View details for PubMedID 40825780

  View details for PubMedCentralID PMC12361475

• Single-cell multiomics identifies both shared and unique features of immune dysfunction in Parkinson's disease and inflammatory bowel disease colon, plasma and stool. bioRxiv : the preprint server for biology Bolen, M. L., Buendia, M., Shi, J., Staley, H., Kachergus, J. M., Efron, P. A., Park, G., Nagpal, R., Alvarez, S. D., Xue, Q., McFarland, N. R., Zimmermann, E. M., Forsmark, C. E., Menees, K. B., Salas, A., Thompson, E. A., Tansey, M. G. 2025

  Abstract

  Parkinson's disease (PD) is the fastest growing neurodegenerative disease in the world 1 . Gastrointestinal (GI) dysfunction can occur decades before motor impairments and in up to 80% of individuals living with PD 2,3,4 . We investigated peripheral relationships that may underlie mechanisms along the gut-blood axis that contribute to PD pathogenesis. Single-cell multiomic spatial molecular imaging (SMI) of colonic tissue localized inflammatory injury within epithelial cells that appear to be associated with iron mishandling in both inflammatory bowel disease (IBD) and PD biosamples. We found that both the single-cell SMI of RNA and protein revealed parallel cross-modal dysregulation in the gut epithelium, in both IBD and PD biosamples. These data are accompanied by plasma (PD) and stool (IBD) protein depletion of CCL22. Our findings suggest iron mishandling along the gut barrier likely contributes to systemic inflammation, which may be the catalyst that primes circulating immune cells to body-first PD pathogenesis.

  View details for DOI 10.1101/2025.04.29.651228

  View details for PubMedID 40661410

• THERAPEUTIC STRATEGIES BASED ON INFLAMMATION/ IMMUNOTHERAPY Tansey, M. G., Bolen, M., Mark, J., Krueger, M., Wallings, R. L. ELSEVIER SCI LTD. 2025

  View details for Web of Science ID 001488156300115

• RGS10 attenuates systemic immune dysregulation induced by chronic inflammatory stress JOURNAL OF NEUROINFLAMMATION Jernigan, J. E., Staley, H. A., Baty, Z., Bolen, M. L., Gomes, B., Holt, J., Cole, C. L., Neighbarger, N. K., Dheeravath, K., Merchak, A. R., Menees, K. B., Coombes, S. A., Tansey, M. 2025; 22 (1): 49

  Abstract

  Regulator of G-protein signaling 10 (RGS10), a key homeostatic regulator of immune cells, has been implicated in multiple diseases associated with aging and chronic inflammation including Parkinson's Disease (PD). Interestingly, subjects with idiopathic PD display reduced levels of RGS10 in subsets of peripheral immune cells. Additionally, individuals with PD have been shown to have increased activated peripheral immune cells in cerebrospinal fluid (CSF) compared to age-matched healthy controls. However, it is unknown whether peripheral immune cells in the CSF of individuals with PD also exhibit decreased levels of RGS10. Utilizing the Michael J. Fox Foundation Parkinson's Progression Markers Initiative (PPMI) study we found that RGS10 levels are decreased in the CSF of individuals with PD compared to healthy controls and prodromal individuals. As RGS10 levels are decreased in the CSF and circulating peripheral immune cells of individuals with PD, we hypothesized that RGS10 regulates peripheral immune cell responses to chronic systemic inflammation (CSI) prior to the onset of neurodegeneration. To test this, we induced CSI for 6 weeks in C57BL6/J mice and RGS10 KO mice to assess circulating and CNS-associated immune cell responses. We found that RGS10 deficiency synergizes with CSI to induce a bias for inflammatory and cytotoxic cell populations, a reduction in antigen presentation machinery in peripheral blood immune cells, as well as in and around the brain that is most notable in males. These results highlight RGS10 as an important regulator of the systemic immune response to CSI and implicate RGS10 as a potential contributor to the development of immune dysregulation in PD.

  View details for DOI 10.1186/s12974-024-03322-1

  View details for Web of Science ID 001429214100002

  View details for PubMedID 39994765

  View details for PubMedCentralID PMC11852585

• Peripheral blood immune cells from individuals with Parkinson's disease or inflammatory bowel disease share deficits in iron storage and transport that are modulated by non-steroidal anti-inflammatory drugs NEUROBIOLOGY OF DISEASE Bolen, M. L., Gomes, B., Gill, B., Menees, K. B., Staley, H., Jernigan, J., Mcfarland, N. R., Zimmermann, E. M., Forsmark, C. E., Tansey, M. 2025; 207: 106794

  Abstract

  Parkinson's Disease (PD) is a multisystem disorder in which dysregulated neuroimmune crosstalk and inflammatory relay via the gut-blood-brain axis have been implicated in PD pathogenesis. Although alterations in circulating inflammatory cytokines and reactive oxygen species (ROS) have been associated with PD, no biomarkers have been identified that predict clinical progression or disease outcome. Gastrointestinal (GI) dysfunction, which involves perturbation of the underlying immune system, is an early and often-overlooked symptom that affects up to 80 % of individuals living with PD. Interestingly, 50-70 % of individuals with inflammatory bowel disease (IBD), a GI condition that has been epidemiologically linked to PD, display chronic illness-induced anemia - which drives toxic accumulation of iron in the gut. Ferroptotic (or iron loaded) cells have small and dysmorphic mitochondria-suggesting that mitochondrial dysfunction is a consequence of iron accumulation. In pro-inflammatory environments, iron accumulates in immune cells, suggesting a possible connection and/or synergy between iron dysregulation and immune cell dysfunction. Peripheral blood mononuclear cells (PBMCs) recapitulate certain PD-associated neuropathological and inflammatory signatures and can act as communicating messengers in the gut-brain axis. Additionally, this communication can be modulated by several environmental factors; specifically, our data further support existing literature demonstrating a role for non-steroidal anti-inflammatory drugs (NSAIDs) in modulating immune transcriptional states in inflamed individuals. A mechanism linking chronic gut inflammation to iron dysregulation and mitochondrial function within peripheral immune cells has yet to be identified in conferring risk for PD. To that end, we isolated PBMCs and simultaneously evaluated their directed transcriptome and bioenergetic status, to investigate if iron dysregulation and mitochondrial sensitization are linked in individuals living with PD or IBD because of chronic underlying remittent immune activation. We have identified shared features of peripheral inflammation and immunometabolism in individuals living with IBD or PD that may contribute to the epidemiological association reported between IBD and risk for PD.

  View details for DOI 10.1016/j.nbd.2025.106794

  View details for Web of Science ID 001428764100001

  View details for PubMedID 39805368

• Multiplex digital spatial profiling identifies subregion dependent targeted proteome changes across variants of dementia. NPJ dementia Bolen, M. L., Menees, K. B., Gearing, M., Gong, J., Ren, Y., Merchak, A. R., Murray, M. E., McEachin, Z. T., Tansey, M. G. 2025; 1 (1): 10

  Abstract

  Frontotemporal lobar degeneration (FTLD) is the leading cause of dementia in patients under the age of 65. Even in a single anatomical region, there is variance within pathological protein deposition within the FTLD spectrum, which drives difficulty in post-mortem clinicopathological diagnoses. We spatially multiplexed the proteome geography at two levels of the cortex and the subcortical white matter in patients with various types of dementia (Alzheimer's disease, C9orf72, MAPT also referred to as FTLD-tau, FTLD-TDP, FTLD-GRN; n=6 per syndrome) and neurologically healthy controls (NHC). Layers II-V of the cortex from diseased individuals displayed the greatest protein dysregulation as compared to NHC. Traditional biomarkers of dementia, like phosphorylated tau proteins and Abeta42 displayed dysregulation, however, our data suggest spatial enrichment distinct to cortical sublayers. In conclusion, the specific localization of these protein deposits could be used to elucidate region-specific pathologic biomarkers unique to individual variants of dementia.

  View details for DOI 10.1038/s44400-025-00010-6

  View details for PubMedID 40476255

• Thinking outside the brain: Gut microbiome influence on innate immunity within neurodegenerative disease NEUROTHERAPEUTICS Merchak, A. R., Bolen, M. L., Tansey, M., Menees, K. B. 2024; 21 (6): e00476

  Abstract

  The complex network of factors that contribute to neurodegeneration have hampered the discovery of effective preventative measures. While much work has focused on brain-first therapeutics, it is becoming evident that physiological changes outside of the brain are the best target for early interventions. Specifically, myeloid cells, including peripheral macrophages and microglia, are a sensitive population of cells whose activity can directly impact neuronal health. Myeloid cell activity includes cytokine production, migration, debris clearance, and phagocytosis. Environmental measures that can modulate these activities range from toxin exposure to diet. However, one of the most influential mediators of myeloid fitness is the gut microenvironment. Here, we review the current data about the role of myeloid cells in gastrointestinal disorders, Parkinson's disease, dementia, and multiple sclerosis. We then delve into the gut microbiota modulating therapies available and clinical evidence for their use in neurodegeneration. Modulating lifestyle and environmental mediators of inflammation are one of the most promising interventions for neurodegeneration and a systematic and concerted effort to examine these factors in healthy aging is the next frontier.

  View details for DOI 10.1016/j.neurot.2024.e00476

  View details for Web of Science ID 001390665400001

  View details for PubMedID 39482179

  View details for PubMedCentralID PMC11585893

• Alzheimer's disease-associated protective variant <i>Plcg2-P522R</i> modulates peripheral macrophage function in a sex-dimorphic manner JOURNAL OF NEUROINFLAMMATION Staley, H. A., Jernigan, J. E., Bolen, M. L., Titus, A. M., Neighbarger, N., Cole, C., Menees, K. B., Wallings, R. L., Tansey, M. 2024; 21 (1): 280

  Abstract

  Genome-wide association studies have identified a protective mutation in the phospholipase C gamma 2 (PLCG2) gene which confers protection against Alzheimer's disease (AD)-associated cognitive decline. Therefore, PLCG2, which is primarily expressed in immune cells, has become a target of interest for potential therapeutic intervention. The protective allele, known as P522R, has been shown to be hyper-morphic in microglia, increasing phagocytosis of amyloid-beta (Aβ), and increasing the release of inflammatory cytokines. However, the effect of this protective mutation on peripheral tissue-resident macrophages, and the extent to which sex modifies this effect, has yet to be assessed. Herein, we show that peripheral macrophages carrying the P522R mutation do indeed show functional differences compared to their wild-type (WT) counterparts, however, these alterations occur in a sex-dependent manner. In macrophages from females, the P522R mutation increases lysosomal protease activity, cytokine secretion, and gene expression associated with cytokine secretion and apoptosis. In contrast, in macrophages from males, the mutation causes decreased phagocytosis and lysosomal protease activity, modest increases in cytokine secretion, and induction of gene expression associated with negative regulation of the immune response. Taken together, these results suggest that the mutation may be conferring different effects dependent on sex and cell type, and highlight the importance of considering sex as a biological variable when assessing the effects of genetic variants and implications for potential immune system-targeted therapies.

  View details for DOI 10.1186/s12974-024-03271-9

  View details for Web of Science ID 001346565100003

  View details for PubMedID 39487477

  View details for PubMedCentralID PMC11529260

• RGS10 Attenuates Systemic Immune Dysregulation Induced by Chronic Inflammatory Stress. bioRxiv : the preprint server for biology Jernigan, J. E., Staley, H. A., Baty, Z., Bolen, M. L., Gomes, B. N., Holt, J., Cole, C. L., Neighbarger, N. K., Dheeravath, K., Merchak, A. R., Menees, K. B., Coombes, S. A., Tansey, M. G. 2024

  Abstract

  Regulator of G-protein signaling 10 (RGS10), a key homeostatic regulator of immune cells, has been implicated in multiple diseases associated with aging and chronic inflammation including Parkinson's Disease (PD). Interestingly, subjects with idiopathic PD display reduced levels of RGS10 in subsets of peripheral immune cells. Additionally, individuals with PD have been shown to have increased activated peripheral immune cells in cerebral spinal fluid (CSF) compared to age-matched healthy controls. However, it is unknown whether CSF-resident peripheral immune cells in individuals with PD also exhibit decreased levels of RGS10. Therefore, we performed an analysis of RGS10 levels in the proteomic database of the CSF from the Michael J. Fox Foundation Parkinson's Progression Markers Initiative (PPMI) study. We found that RGS10 levels are decreased in the CSF of individuals with PD compared to healthy controls and prodromal individuals. Moreover, we find that RGS10 levels decrease with age but not PD progression and that males have less RGS10 than females in PD. Importantly, studies have established an association between chronic systemic inflammation (CSI) and neurodegenerative diseases, such as PD, and known sources of CSI have been identified as risk factors for developing PD; however, the role of peripheral immune cell dysregulation in this process has been underexplored. As RGS10 levels are decreased in the CSF and circulating peripheral immune cells of individuals with PD, we hypothesized that RGS10 regulates peripheral immune cell responses to CSI prior to the onset of neurodegeneration. To test this, we induced CSI for 6 weeks in C57BL6/J mice and RGS10 KO mice to assess circulating and CNS-associated peripheral immune cell responses. We found that RGS10 deficiency synergizes with CSI to induce a bias for inflammatory and cytotoxic cell populations, a reduction in antigen presentation in peripheral blood immune cells, as well as in and around the brain that is most notable in males. These results highlight RGS10 as an important regulator of the systemic immune response to CSI and implicate RGS10 as a potential contributor to the development of immune dysregulation in PD.

  View details for DOI 10.1101/2024.10.24.620078

  View details for PubMedID 39554164

• Peripheral Blood Immune Cells from Individuals with Parkinson's Disease or Inflammatory Bowel Disease Share Deficits in Iron Storage and Transport that are Modulated by Non-Steroidal Anti-Inflammatory Drugs. bioRxiv : the preprint server for biology Bolen, M. L., Nunes Gomes, B., Gill, B., Menees, K. B., Staley, H., Jernigan, J., Tansey, M. G. 2024

  Abstract

  Parkinson's Disease (PD) is a multisystem disorder in which dysregulated neuroimmune crosstalk and inflammatory relay via the gut-blood-brain axis have been implicated in PD pathogenesis. Although alterations in circulating inflammatory cytokines and reactive oxygen species (ROS) have been associated with PD, no biomarkers have been identified that predict clinical progression or disease outcome. Gastrointestinal (GI) dysfunction, which involves perturbation of the underlying immune system, is an early and often-overlooked symptom that affects up to 80% of individuals living with PD. Interestingly, 50-70% of individuals with inflammatory bowel disease (IBD), a GI condition that has been epidemiologically linked to PD, display chronic illness-induced anemia - which drives toxic accumulation of iron in the gut. Ferroptotic (or iron loaded) cells have small and dysmorphic mitochondria-suggesting that mitochondrial dysfunction is a consequence of iron accumulation. In pro-inflammatory environments, iron accumulates in immune cells, suggesting a possible connection and/or synergy between iron dysregulation and immune cell dysfunction. Peripheral blood mononuclear cells (PBMCs) recapitulate certain PD-associated neuropathological and inflammatory signatures and can act as communicating messengers in the gut-brain axis. Additionally, this communication can be modulated by several environmental factors; specifically, our data further support existing literature demonstrating a role for non-steroidal anti-inflammatory drugs (NSAIDs) in modulating immune transcriptional states in inflamed individuals. A mechanism linking chronic gut inflammation to iron dysregulation and mitochondrial function within peripheral immune cells has yet to be identified in conferring risk for PD. To that end, we isolated PBMCs and simultaneously evaluated their directed transcriptome and bioenergetic status, to investigate if iron dysregulation and mitochondrial sensitization are linked in individuals living with PD or IBD because of chronic underlying remittent immune activation. We have identified shared features of peripheral inflammation and immunometabolism in individuals living with IBD or PD that may contribute to the epidemiological association reported between IBD and risk for PD.

  View details for DOI 10.1101/2024.08.19.608634

  View details for PubMedID 39229100

• Diet-induced metabolic and immune impairments are sex-specifically modulated by soluble TNF signaling in the 5xFAD mouse model of Alzheimer's disease NEUROBIOLOGY OF DISEASE De Sousa Rodrigues, M., Bolen, M. L., Blackmer-Raynolds, L., Schwartz, N., Chang, J., Tansey, M., Sampson, T. 2024; 196: 106511

  Abstract

  Emerging evidence indicates that high-fat, high carbohydrate diet (HFHC) impacts central pathological features of Alzheimer's disease (AD) across both human incidences and animal models. However, the mechanisms underlying this association are poorly understood. Here, we identify compartment-specific metabolic and inflammatory dysregulations that are induced by HFHC diet in the 5xFAD mouse model of AD pathology. We observe that both male and female 5xFAD mice display exacerbated adiposity, cholesterolemia, and dysregulated insulin signaling. Independent of biological sex, HFHC diet also resulted in altered inflammatory cytokine profiles across the gastrointestinal, circulating, and central nervous systems (CNS) compartments demonstrating region-specific impacts of metabolic inflammation. Interestingly, inhibiting the inflammatory cytokine, soluble tumor necrosis factor (TNF) with the brain-permeant soluble TNF inhibitor XPro1595 was able to restore aspects of HFHC-induced metabolic inflammation, but only in male mice. Targeted transcriptomics of CNS regions revealed that inhibition of soluble TNF was sufficient to alter expression of hippocampal and cortical genes associated with beneficial immune and metabolic responses. Collectively, these results suggest that HFHC diet impairs metabolic and inflammatory pathways in an AD-relevant genotype and that soluble TNF has sex-dependent roles in modulating these pathways across anatomical compartments. Modulation of energy homeostasis and inflammation may provide new therapeutic avenues for AD.

  View details for DOI 10.1016/j.nbd.2024.106511

  View details for Web of Science ID 001240408100001

  View details for PubMedID 38670277

• Diet-induced metabolic and immune impairments are sex-specifically modulated by soluble TNF signaling in the 5xFAD mouse model of Alzheimer's disease. bioRxiv : the preprint server for biology De Sousa Rodrigues, M. E., Bolen, M. L., Blackmer-Raynolds, L., Schwartz, N., Chang, J., Tansey, M. G., Sampson, T. R. 2024

  Abstract

  Emerging evidence indicates that high-fat, high carbohydrate diet (HFHC) impacts central pathological features of Alzheimer's disease (AD) across both human incidences and animal models. However, the mechanisms underlying this association are poorly understood. Here, we identify compartment-specific metabolic and inflammatory dysregulations that are induced by HFHC diet in the 5xFAD mouse model of AD pathology. We observe that both male and female 5xFAD mice display exacerbated adiposity, cholesterolemia, and dysregulated insulin signaling. Independent of biological sex, HFHC diet also resulted in altered inflammatory cytokine profiles across the gastrointestinal, circulating, and central nervous systems (CNS) compartments demonstrating region-specific impacts of metabolic inflammation. In male mice, we note that HFHC triggered increases in amyloid beta, an observation not seen in female mice. Interestingly, inhibiting the inflammatory cytokine, soluble tumor necrosis factor (TNF) with the brain-permeant soluble TNF inhibitor XPro1595 was able to restore aspects of HFHC-induced metabolic inflammation, but only in male mice. Targeted transcriptomics of CNS regions revealed that inhibition of soluble TNF was sufficient to alter expression of hippocampal and cortical genes associated with beneficial immune and metabolic responses. Collectively, these results suggest that HFHC diet impairs metabolic and inflammatory pathways in an AD-relevant genotype and that soluble TNF has sex-dependent roles in modulating these pathways across anatomical compartments. Modulation of energy homeostasis and inflammation may provide new therapeutic avenues for AD.

  View details for DOI 10.1101/2024.02.28.582516

  View details for PubMedID 38464096

• Complement C1q-dependent engulfment of alpha-synuclein induces ENS-resident macrophage exhaustion and accelerates Parkinson's-like gut pathology. bioRxiv : the preprint server for biology Mackie, P. M., Koshy, J., Bhogade, M., Hammoor, T., Hachmeister, W., Lloyd, G. M., Paterno, G., Bolen, M., Tansey, M. G., Giasson, B. I., Khoshbouei, H. 2023

  Abstract

  Deposition of misfolded alpha-synuclein (alphasyn) in the enteric nervous system (ENS) is found in multiple neurodegenerative diseases. It is hypothesized that ENS synucleinopathy contributes to both the pathogenesis and non-motor morbidity in Parkinson's Disease (PD), but the cellular and molecular mechanisms that shape enteric histopathology and dysfunction are poorly understood. Here, we demonstrate that ENS-resident macrophages, which play a critical role in maintaining ENS homeostasis, initially respond to enteric neuronal alphasyn pathology by upregulating machinery for complement-mediated engulfment. Pharmacologic depletion of ENS-macrophages or genetic deletion of C1q enhanced enteric neuropathology. Conversely, C1q deletion ameliorated gut dysfunction, indicating that complement partially mediates alphasyn-induced gut dysfunction. Internalization of alphasyn led to increased endo-lysosomal stress that resulted in macrophage exhaustion and temporally correlated with the progression of ENS pathology. These novel findings highlight the importance of enteric neuron-macrophage interactions in removing toxic protein aggregates that putatively shape the earliest stages of PD in the periphery.

  View details for DOI 10.1101/2023.10.24.563832

  View details for PubMedID 37961460

• PERK KNOCKDOWN PROTECTS AGAINST REPETITIVE MILD TRAUMATIC BRAIN INJURY-INDUCED CHANGES IN FUNCTIONAL CONNECTIVITY AND ALTERS THE EXPRESSION OF DISEASE-ASSOCIATED PROTEINS Ravi, S., Criado-Marrero, M., Bolen, M., Barroso, D., Rubinovich, U., Hery, G. P., Grudny, M. M., Prokop, S., Febo, M., Abisambra, J. MARY ANN LIEBERT, INC. 2023: A113

  View details for Web of Science ID 001093595400364

• Fixed Time-Point Analysis Reveals Repetitive Mild Traumatic Brain Injury Effects on Resting State Functional Magnetic Resonance Imaging Connectivity and Neuro-Spatial Protein Profiles JOURNAL OF NEUROTRAUMA Sakthivel, R., Criado-Marrero, M., Barroso, D., Braga, I. M. M., Bolen, M., Rubinovich, U., Hery, G. P. P., Grudny, M. M. M., Koren, J., Prokop, S., Febo, M., Abisambra, J. 2023; 40 (19-20): 2037-2049

  Abstract

  Repetitive mild traumatic brain injuries (rmTBIs) are serious trauma events responsible for the development of numerous neurodegenerative disorders. A major challenge in developing diagnostics and treatments for the consequences of rmTBI is the fundamental knowledge gaps of the molecular mechanisms responsible for neurodegeneration. It is both critical and urgent to understand the neuropathological and functional consequences of rmTBI to develop effective therapeutic strategies. Using the Closed-Head Impact Model of Engineered Rotational Acceleration, or CHIMERA, we measured neural changes following injury, including brain volume, diffusion tensor imaging, and resting-state functional magnetic resonance imaging coupled with graph theory and functional connectivity analyses. We determined the effect of rmTBI on markers of gliosis and used NanoString-GeoMx to add a digital-spatial protein profiling analysis of neurodegenerative disease-associated proteins in gray and white matter regions. Our analyses revealed aberrant connectivity changes in the thalamus, independent of microstructural damage or neuroinflammation. We also identified distinct changes in the levels of proteins linked to various neurodegenerative processes including total and phospho-tau species and cell proliferation markers. Together, our data show that rmTBI significantly alters brain functional connectivity and causes distinct protein changes in morphologically intact brain areas.

  View details for DOI 10.1089/neu.2022.0464

  View details for Web of Science ID 000976080400001

  View details for PubMedID 37051703

  View details for PubMedCentralID PMC10541943

• DIGITAL SPATIAL PROTEOMIC PROFILING IDENTIFIES REGION SPECIFIC CHANGES FOLLOWING REPETITIVE MILD TRAUMATIC BRAIN INJURY IN MICE Bolen, M., Ravi, S., Abisambra, J. MARY ANN LIEBERT, INC. 2022: A14

  View details for Web of Science ID 000840122300054

• REPETITIVE MILD TRAUMATIC BRAIN INJURY PROMOTES INFLAMMATION AND DISRUPTS FUNCTIONAL CONNECTIVITY IN THALAMIC NUCLEI Ravi, S., Braga, I. M., Bolen, M., Barroso, D., Rubinovich, U., Grudny, M. M., Febo, M., Abisambra, J. MARY ANN LIEBERT, INC. 2022: A28-A29

  View details for Web of Science ID 000840122300095