Preparing Extension Professionals: The Ohio State University\u27s Model of Extension Education

Extension systems throughout the United States require individuals to have college degrees to work as Extension professionals. This article shares The Ohio State University\u27s approach to Extension Education in the Department of Human and Community Resource Development. A model is presented for preparing Extension professionals in an academic setting. Based on the research literature, competencies for success in Extension are matched with courses at the undergraduate and graduate levels of instruction. By sharing our approach, we hope to encourage dialogue and discussion that will help us and other academic programs to offer the best possible curriculum for preparing Extension educators

Changes in glial cell phenotypes precede overt neurofibrillary tangle formation, correlate with markers of cortical cell damage, and predict cognitive status of individuals at Braak III-IV stages

Clinico-pathological correlation studies show that some otherwise healthy elderly individuals who never developed cognitive impairment harbor a burden of Alzheimer’s disease lesions (plaques and tangles) that would be expected to result in dementia. In the absence of comorbidities explaining such discrepancies, there is a need to identify other brain changes that meaningfully contribute to the cognitive status of an individual in the face of such burdens of plaques and tangles. Glial inflammatory responses, a universal phenomenon in symptomatic AD, show robust association with degree of cognitive impairment, but their significance in early tau pathology stages and contribution to the trajectory of cognitive decline at an individual level remain widely unexplored. We studied 55 brains from individuals at intermediate stages of tau tangle pathology (Braak III-IV) with diverging antemortem cognition (demented vs. non-demented, here termed `resilient’), and age-matched cognitively normal controls (Braak 0-II). We conducted quantitative assessments of amyloid and tau lesions, cellular vulnerability markers, and glial phenotypes in temporal pole (Braak III-IV region) and visual cortex (Braak V-VI region) using artificial-intelligence based semiautomated quantifications. We found distinct glial responses with increased proinflammatory and decreased homeostatic markers, both in regions with tau tangles (temporal pole) and without overt tau deposits (visual cortex) in demented but not in resilient. These changes were significantly associated with markers of cortical cell damage. Similar phenotypic glial changes were detected in the white matter of demented but not resilient and were associated with higher burden of overlying cortical cellular damage in regions with and without tangles. Our data suggest that changes in glial phenotypes in cortical and subcortical regions represent an early phenomenon that precedes overt tau deposition and likely contributes to cell damage and loss of brain function predicting the cognitive status of individuals at intermediate stages of tau aggregate burden (Braak III-IV)

Tau Oligomer–Containing Synapse Elimination by Microglia and Astrocytes in Alzheimer Disease

Importance: Factors associated with synapse loss beyond amyloid-β plaques and neurofibrillary tangles may more closely correlate with the emergence of cognitive deficits in Alzheimer disease (AD) and be relevant for early therapeutic intervention. // Objective: To investigate whether accumulation of tau oligomers in synapses is associated with excessive synapse elimination by microglia or astrocytes and with cognitive outcomes (dementia vs no dementia [hereinafter termed resilient]) of individuals with equal burdens of AD neuropathologic changes at autopsy. // Design, Setting, and Participants: This cross-sectional postmortem study included 40 human brains from the Massachusetts Alzheimer Disease Research Center Brain Bank with Braak III to IV stages of tau pathology but divergent antemortem cognition (dementia vs resilient) and cognitively normal controls with negligible AD neuropathologic changes. The visual cortex, a region without tau tangle deposition at Braak III to IV stages, was assessed after expansion microscopy to analyze spatial relationships of synapses with microglia and astrocytes. Participants were matched for age, sex, and apolipoprotein E status. Evidence of Lewy bodies, TDP-43 aggregates, or other lesions different from AD neuropathology were exclusion criteria. Tissue was collected from July 1998 to November 2020, and analyses were conducted from February 1, 2022, through May 31, 2023. // Main Outcomes and Measures: Amyloid-β plaques, tau neuropil thread burden, synapse density, tau oligomers in synapses, and internalization of tau oligomer–tagged synapses by microglia and astrocytes were quantitated. Analyses were performed using 1-way analysis of variance for parametric variables and the Kruskal-Wallis test for nonparametric variables; between-group differences were evaluated with Holm-Šídák tests. // Results: Of 40 included participants (mean [SD] age at death, 88 [8] years; 21 [52%] male), 19 had early-stage dementia with Braak stages III to IV, 13 had resilient brains with similar Braak stages III to IV, and 8 had no dementia (Braak stages 0-II). Brains with dementia but not resilient brains had substantial loss of presynaptic (43%), postsynaptic (33%), and colocalized mature synaptic elements (38%) compared with controls and significantly higher percentages of mature synapses internalized by IBA1-positive microglia (mean [SD], 13.3% [3.9%] in dementia vs 2.6% [1.9%] in resilient vs 0.9% [0.5%] in control; P < .001) and by GFAP-positive astrocytes (mean [SD], 17.2% [10.9%] in dementia vs 3.7% [4.0%] in resilient vs 2.7% [1.8%] in control; P = .001). In brains with dementia but not in resilient brains, tau oligomers more often colocalized with synapses, and the proportions of tau oligomer–containing synapses inside microglia (mean [SD] for presynapses, mean [SD], 7.4% [1.8%] in dementia vs 5.1% [1.9%] resilient vs 3.7% [0.8%] control; P = .006; and for postsynapses 11.6% [3.6%] dementia vs 6.8% [1.3%] resilient vs 7.4% [2.5%] control; P = .001) and astrocytes (mean [SD] for presynapses, 7.0% [2.1%] dementia vs 4.3% [2.2%] resilient vs 4.0% [0.7%] control; P = .001; and for postsynapses, 7.9% [2.2%] dementia vs 5.3% [1.8%] resilient vs 3.0% [1.5%] control; P < .001) were significantly increased compared with controls. Those changes in brains with dementia occurred in the absence of tau tangle deposition in visual cortex. // Conclusion and Relevance: The findings from this cross-sectional study suggest that microglia and astrocytes may excessively engulf synapses in brains of individuals with dementia and that the abnormal presence of tau oligomers in synapses may serve as signals for increased glial-mediated synapse elimination and early loss of brain function in AD

Common mouse models of tauopathy reflect early but not late human disease

BACKGROUND: Mouse models that overexpress human mutant Tau (P301S and P301L) are commonly used in preclinical studies of Alzheimer’s Disease (AD) and while several drugs showed therapeutic effects in these mice, they were ineffective in humans. This leads to the question to which extent the murine models reflect human Tau pathology on the molecular level. METHODS: We isolated insoluble, aggregated Tau species from two common AD mouse models during different stages of disease and characterized the modification landscape of the aggregated Tau using targeted and untargeted mass spectrometry-based proteomics. The results were compared to human AD and to human patients that suffered from early onset dementia and that carry the P301L Tau mutation. RESULTS: Both mouse models accumulate insoluble Tau species during disease. The Tau aggregation is driven by progressive phosphorylation within the proline rich domain and the C-terminus of the protein. This is reflective of early disease stages of human AD and of the pathology of dementia patients carrying the P301L Tau mutation. However, Tau ubiquitination and acetylation, which are important to late-stage human AD are not represented in the mouse models. CONCLUSION: AD mouse models that overexpress human Tau using risk mutations are a suitable tool for testing drug candidates that aim to intervene in the early formation of insoluble Tau species promoted by increased phosphorylation of Tau. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13024-023-00601-y

Regulation of Tau Expression in Superior Cervical Ganglion (SCG) Neurons In Vivo and In Vitro

The superior cervical ganglion (SCG) is part of the autonomic nervous system providing sympathetic innervation to the head and neck, and has been regularly used to prepare postnatal neuronal cultures for cell biological studies. We found that during development these neurons change tau expression from the low molecular weight (LMW) isoforms to Big tau, with the potential to affect functions associated with tau such as microtubule dynamic and axonal transport. Big tau contains the large 4a exon that transforms tau from LMW isoforms of 45–60 kDa to 110 kDa. We describe tau expression during postnatal development reporting that the transition from LMW tau to Big tau which started at late embryonic stages is completed by about 4–5 weeks postnatally. We confirmed the presence of Big tau in dissociated postnatal SCG neurons making them an ideal system to study the function of Big tau in neurons. We used SCG explants to examine the response of SCG neurons to lesion and found that Big tau expression returned gradually along the regrowing neurites suggesting that it does not drives regeneration, but facilitates the structure/function of mature SCG neurons. The structural/functional roles of Big tau remain unknown, but it is intriguing that neurons that express Big tau appear less vulnerable to tauopathies

Preparing Extension Professionals: The Ohio State University\u27s Model of Extension Education

Extension systems throughout the United States require individuals to have college degrees to work as Extension professionals. This article shares The Ohio State University\u27s approach to Extension Education in the Department of Human and Community Resource Development. A model is presented for preparing Extension professionals in an academic setting. Based on the research literature, competencies for success in Extension are matched with courses at the undergraduate and graduate levels of instruction. By sharing our approach, we hope to encourage dialogue and discussion that will help us and other academic programs to offer the best possible curriculum for preparing Extension educators

Transplanting Neural Progenitor Cells into a Chronic Dorsal Column Lesion Model

Cell transplantation therapy is a promising strategy for spinal cord injury (SCI) repair. Despite advancements in the development of therapeutic strategies in acute and subacute SCI, much less is known about effective strategies for chronic SCI. In previous studies we demonstrated that transplants of neural progenitor cells (NPC) created a permissive environment for axon regeneration and formed a neuronal relay across the injury following an acute dorsal column injury. Here we explored the efficacy of such a strategy in a chronic injury. We tested two preparations of NPCs derived from rat spinal cord at embryonic day 13.5: one prepared using stocks of cultured cells and the other of dissociated cells transplanted without culturing. Transplantation was delayed for 4-, 6- and 12-weeks post injury for a chronic injury model. We found that the dissociated NPC transplants survived and proliferated for at least 5 weeks post transplantation, in contrast to the poor survival of transplants prepared from cultured NPC stocks. The dissociated NPC transplants differentiated into neurons expressing excitatory markers, promoted axon regeneration into the injury/transplant site and extended axons from graft-derived neurons into the host. These results support the potential of NPC transplants to form neuronal relays across a chronic SCI, but they also underscore the challenges of achieving efficient cell survival in the environment of a chronic injury