Biology subjects

Thomson, B.

Publications and source records attributed to Thomson, B..

3 recordsLinked to original sources

bioRxiv2026

Exploring the PLD1-tau interaction in Frontotemporal Dementia.

SummaryFrontotemporal dementia (FTD), a leading cause of young-onset dementia, is characterized by progressive behavioral and cognitive decline associated with frontotemporal cortical atrophy. Nearly 40% of cases exhibit tauopathy, yet the molecular drivers of tau aggregation leading to synaptic dysfunction remain poorly understood. Here, we investigated whether Phospholipase D1 (PLD1, a lipid signaling enzyme), implicated in Alzheimers disease (AD), and amyotrophic lateral sclerosis (ALS), contributes to tau pathology dependent synaptic deficits in FTD. Postmortem temporal (BA38) and frontal (BA9) cortices from clinically diagnosed FTD and age-matched control subjects were analyzed using fluorescence-assisted single synaptosome long-term potentiation (FASS-LTP), immunofluorescence, proximity ligation assays (PLA), and PLD1-interactome proteomics. FASS-LTP revealed markedly reduced glutamatergic potentiation in BA38 and BA9 crude synaptoneurosomes from FTD brains compared to controls. Western blotting demonstrated elevated PLD1 expression in both crude synaptoneurosomal and cytosolic fractions from FTD subjects in BA38, but not BA9. Bielschowsky staining confirmed increased Pick body burden in FTD temporal cortex. Immunofluorescence and PLA showed robust PLD1 co-localization with total tau (HT7), hyperphosphorylated tau (AT8), and acetylated tau oligomers (TOMA2), indicating a strong spatial association between PLD1 and pathological tau species. PLD1 also exhibited enhanced co-localization with astrocytic GFAP and synaptic markers (PSD95, Nrx1{beta}), suggesting compartmentalized involvement in glial and synaptic remodeling. Proteomic profiling of PLD1-associated complexes revealed compartment-specific alterations with cytosolic fractions enriched for metabolic enzymes, stress-response proteins, and GFAP, while crude synaptoneurosomal fractions showed depletion of presynaptic scaffolds, vesicle-trafficking regulators, and proteostasis components. Cross-compartment integration indicated that over one-third of proteins were redistributed from synapses to cytosol, consistent with trafficking and degradative impairments. Gene Ontology analysis highlighted lipid metabolism, astrocyte activation, and proteasome dysfunction as dominant pathways. Collectively, these findings identify PLD1 as a critical mediator of synaptic dysfunction and tau pathology in FTD, acting through astroglial activation and disrupting synaptic proteostasis. This study provides the human clinical relevance towards PLD1 attenuation as a therapeutic target for FTD and related tauopathies to mitigate tau-driven neurodegeneration and restore synaptic integrity.

neuroscience↗

bioRxiv2026

Ultrastructural and Histological Cryopreservation of Mammalian Brains by Vitrification

Studies of whole brain cryopreservation are rare but are potentially important for a variety of applications. It has been demonstrated that ultrastructure in whole rabbit and pig brains can be cryopreserved by vitrification (ice-free cryopreservation) after prior aldehyde fixation, but fixation limits the range of studies that can be done by neurobiologists, including studies that depend upon general molecular integrity, signal transduction, macromolecular synthesis, and other physiological processes. We now show that whole brain ultrastructure can be preserved by vitrification without prior aldehyde fixation. Rabbit brain perfusion with the M22 vitrification solution followed by vitrification, warming, and fixation showed an absence of visible ice damage and overall structural preservation, but osmotic brain shrinkage sufficient to distort and obscure neuroanatomical detail. Neuroanatomical preservation in the presence of M22 was also investigated in human cerebral cortical biopsies taken after whole brain perfusion with M22. These biopsies did not form ice upon cooling or warming, and high power electron microscopy showed dehydrated and electron-dense but predominantly intact cells, neuropil, and synapses with no signs of ice crystal damage, and partial dilution of these samples restored normal cortical pyramidal cell shapes. To further evaluate ultrastructural preservation within the severely dehydrated brain, rabbit brains were perfused with M22 and then partially washed free of M22 before fixation. Perfusion dilution of the brain to 3-5M M22 resulted in brain re-expansion and the re-appearance of well-defined neuroanatomical features, but rehydration of the brain to 1M M22 resulted in ultrastructural damage suggestive of preventable osmotic injury caused by incomplete removal of M22. We conclude that both animal and human brains can be cryopreserved by vitrification with predominant retention of ultrastructural integrity without the need for prior aldehyde fixation. This observation has direct relevance to the feasibility of human cryopreservation, for which direct evidence has been lacking until this report. It also provides a starting point for perfecting brain cryopreservation, which may be necessary for lengthy space travel and could allow future medical time travel.

neuroscience↗

bioRxiv2021

Microbial rhodopsins are increasingly favored over chlorophyll in High Nutrient Low Chlorophyll waters

Microbial rhodopsins are simple light-harvesting complexes that, unlike chlorophyll photosystems, have no iron requirements for their synthesis and phototrophic functions. Here we report the first environmental concentrations of rhodopsin along the Subtropical Frontal Zone off New Zealand, where Subtropical waters encounter the iron-limited Subantarctic High Nutrient Low Chlorophyll (HNLC) region. Rhodopsin concentrations were highest in HNLC waters where chlorophyll-a concentrations were lowest. Furthermore, while the ratio of rhodopsin to chlorophyll-a photosystems was on average 20 along the transect, this ratio increased to over 60 in HNLC waters. We further show that microbial rhodopsins are abundant in both picoplankton (0.2-3m) and in the larger (>3m) size fractions of the microbial community containing eukaryotic plankton and/or particle-attached prokaryotes. These findings suggest that rhodopsin phototrophy could be critical for microbial plankton to adapt to resource-limiting environments where photosynthesis and possibly cellular respiration are impaired. Originality-Significance statementHigh Nutrient Low Chlorophyll (HNLC) regimes cover approximately 30% of the global ocean surface and play a crucial role in the Earths carbon cycle. Here we show that microbial rhodopsins are particularly abundant in a HNLC region of the Subantarctic ocean, where chlorophyll abundance is relatively low and photosynthesis and respiration might be impaired due to iron limitation. These data suggest that rhodopsin phototrophy can contribute significantly to the energy budgets of HNLC regions, capturing meaningful amounts of light that cannot be channeled through photosynthesis.

ecology↗