Gut Bacteria Can Cause Alzheimer's ???

Hello, Summarians!

Welcome to the brain function edition. This highlights a couple of ways that illustrate how external factors can greatly influence the brain. To be honest, it is sometimes amazing that the brain doesn’t show up with more issues.

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COVID and Brain Changes in Dogs

Since the emergence of SARS-CoV-2 in late 2019, it has primarily affected humans, but various animal species have also been infected due to their similarity in the ACE2 receptor with humans. Infected animals, including dogs, show clinical signs similar to humans, raising concerns about potential virus transmission between humans and animals. Close interaction between humans and dogs, along with their genetic similarity, has led to investigations into dogs' susceptibility to SARS-CoV-2. Studies have shown that dogs can be infected, produce neutralizing antibodies, and exhibit histopathological changes in lung tissues, indicating potential cross-species transmission. SARS-CoV-2 has been associated with neurological symptoms in humans, including headache, fatigue, and cognitive dysfunction. It can also lead to brain pathologies, such as reduced cortical thickness. This has raised concerns about potential long-term neurodegenerative effects. The exact cause of SARS-CoV-2-induced neuropathological changes remains unclear, but evidence suggests vascular damage and immune responses in the brain as major factors. Brain imaging has detected white matter hyperintensities, indicative of blood-brain barrier (BBB) damage, and neuroinflammatory responses in infected patients. To investigate dogs' susceptibility to SARS-CoV-2, a study was conducted using the Delta variant. Dogs were kept in a controlled environment, and the study showed that SARS-CoV-2 could infect dogs and be transmitted through direct contact, leading to pathological changes in the brain and lungs, even without evident clinical signs. SARS-CoV-2 was detected in the nasal and oral secretions of infected dogs, with higher viral titers in dogs exposed to infected ones. Dogs in the contact group exhibited more severe inflammatory responses in the upper respiratory tract. Seroconversion in dogs occurred early in the infection, even before clinical signs appeared, and neutralizing antibody levels correlated with spike protein antibodies. Lung pathology in infected dogs included thickening of the alveolar septum, interstitial pneumonia, and perivasculitis. Brain pathology showed damage to the blood-brain barrier, similar to small vessel disease (SVD) observed in humans. This damage led to neuroinflammatory responses, activation of glial cells, and axonopathy, even when the virus had cleared from the brain. Phosphorylated tau protein, associated with Alzheimer's disease, was detected, suggesting a potential for neurodegenerative diseases in SARS-CoV-2-infected brains. The study highlights the possibility of long-term brain damage induced by SARS-CoV-2 in dogs and suggests that even asymptomatic human patients may experience neuropathological changes. The research compared two infection routes and used dogs as a more relevant model for human studies, providing insights into potential neuropathological changes in humans. 

Kim D-H, Kim D-Y, Kim K-S, Han S-H, Go H-J, Kim J-H, et al. Neurologic effects of SARS-CoV-2 transmitted among dogs. Emerg Infect Dis. 2023 Nov. https://doi.org/10.3201/eid2911.230804 

Bottom line — COVID may cause long-term brain changes.

Gut Bacteria and the Brain

Alzheimer's disease is a complex neurodegenerative disorder characterized by cognitive decline and neuropsychiatric symptoms. Key hallmarks include the buildup of amyloid-β plaques, neurofibrillary tangles, inflammation, and neuronal death, with the hippocampus being particularly vulnerable. Adult hippocampal neurogenesis (AHN), the process of generating new neurons in the hippocampus, plays a crucial role in cognitive function and emotion regulation but is impaired in Alzheimer's. Alzheimer's is influenced by genetic, lifestyle, and environmental factors, and emerging research is focusing on the gut microbiome due to its susceptibility to lifestyle and environmental changes. Alterations in the gut microbiota have been observed in Alzheimer's patients, and there is a genetic connection between Alzheimer's and gastrointestinal disorders. Studies in mice have shown that the gut microbiota can influence Alzheimer's pathology and cognitive function. However, it remains unexplored whether cognitive symptoms and AHN changes in Alzheimer's patients can be transmitted to healthy organisms through the gut microbiota. To address this, researchers conducted fecal microbiota transplantation (FMT) from Alzheimer's patients into young rats and assessed behavioral, neurogenic, and metabolic effects. They also studied the impact of Alzheimer's serum on human hippocampal progenitor cells in vitro to understand the role of AHN in Alzheimer's. The study demonstrated that transplantation of gut microbiota from Alzheimer's patients into healthy rats induced core cognitive symptoms and impaired AHN. Alzheimer's serum also negatively affected AHN in human cells in vitro, highlighting AHN as a crucial process affected by both systemic and gut factors in Alzheimer's disease. The results confirmed the presence of systemic and gut inflammation in Alzheimer's patients. Changes in the gut microbiota composition, including decreased Firmicutes and increased Bacteroidetes, were consistent with previous findings. However, it's essential to consider geographic and methodological variations in microbiota studies. Donor-specific factors influenced the engraftment of microbiota in rats, emphasizing the need for comprehensive assessments of lifestyle factors and other influences on the gut microbiota. Behavioral tests in rats revealed reduced pattern separation, impaired spatial memory, and recognition memory in those colonized with microbiota from Alzheimer's patients. These cognitive impairments were linked to AHN changes. In human-derived hippocampal progenitor cells, Alzheimer's serum decreased neurogenesis-related markers, although cell death patterns differed during disease progression. Neurite outgrowth was enhanced under Alzheimer's serum conditions, which could be influenced by differences in cell maturity. The study also found correlations between specific microbiota genera and neurogenic readouts, suggesting a complex relationship between lifestyle factors, microbiota, and cognitive function. The composition of the gut microbiota was associated with changes in caecal and hippocampal metabolomes, potentially linking microbiota to AHN and cognitive changes. In conclusion, this research demonstrates that the gut microbiota from Alzheimer's patients can induce Alzheimer's-like symptoms in healthy organisms, confirming the gut microbiota's role in the disease. Additionally, AHN is identified as a central cellular process influenced by both systemic and gut-mediated factors in Alzheimer's disease. 

Stefanie Grabrucker, Moira Marizzoni, Edina Silajdžić, Nicola Lopizzo, Elisa Mombelli, Sarah Nicolas, Sebastian Dohm-Hansen, Catia Scassellati, Davide Vito Moretti, Melissa Rosa, Karina Hoffmann, John F Cryan, Olivia F O’Leary, Jane A English, Aonghus Lavelle, Cora O’Neill, Sandrine Thuret, Annamaria Cattaneo, Yvonne M Nolan, Microbiota from Alzheimer’s patients induce deficits in cognition and hippocampal neurogenesis, Brain https://doi.org/10.1093/brain/awad303 

 
 Bottom line — Biome can influence brain pathology and function

CBD and Horses

This study investigated the pharmacokinetics of cannabidiol (CBD) in horses through intravenous and oral administration using different formulations. The research involved eight healthy horses and included an analysis of CBD in sesame oil and a micellar formulation. The findings revealed that CBD exhibited a high volume of distribution, a relatively high systemic clearance, and extended half-lives in horses. The oral bioavailability of CBD was approximately 14% for both formulations, indicating limited absorption when given orally.Notably, the micellar formulation resulted in faster absorption and a higher concentration peak in the bloodstream, while the oil formulation yielded lower but sustained levels over time. Simulations suggested that both formulations, at a dose of 10.00 mg/kg, could be suitable for multiple oral dose treatments, with similar percentages reaching effective plasma concentrations when administered every 12 or 24 hours. Importantly, no adverse reactions were observed in the horses across different doses and routes of administration.In clinical terms, these findings suggest that CBD may hold promise for potential use in horses, but further research and clinical studies are necessary to evaluate its safety and efficacy fully. One limitation of the study was the relatively small horse population used, which may impact the generalizability of the results.

Sánchez de Medina, A, Serrano-Rodríguez, JM, Díez de Castro, E, García-Valverde, MT, Saitua, A, Becero, M, et al. Pharmacokinetics and oral bioavailability of cannabidiol in horses after intravenous and oral administration with oil and micellar formulations.Equine Vet J. 2023; 55(6): 1094–1103. https://doi.org/10.1111/evj.13923 

Bottom line — Good kinetic information on CBD in horses.

Just putting things in perspective …