Given the many toxicant components found in cannabis smokers, it is not surprising that cannabis smoking notably alters the oral microbial ecology. Importantly,long-term repeated oral inoculation of A. meyeri, which mimicked cannabis exposure-increased oral A. meyeri in humans, resulted in the development of CNS abnormalities.Recent studies have found correlations between Actinomyces and Alzheimer’s disease. For example, brains from patients with Alzheimer’s disease have been reported to have strikingly large bacterial loads compared to controls . Actinobacteria, a phylum of Actinomyces,were exclusively detected in the post mortem brain samples from patients with Alzheimer’s disease compared with those of normal brains . Actinobacteria were also found enriched in the gutmicrobiota of patients with Alzheimer’s disease . Another study using 16S rDNA sequencing in the brain cell lysates further found Actinomycetales, Prevotella, Treponema,cannabis grow system and Veillonella were exclusively present in the brain of patients with Alzheimer’s disease .
In a previous study, oral microbiome and resting-state functional magnetic resonance imaging scans were conducted in cannabis smokers; the enrichment of Actinomyces in the oral microbiome was positively correlated with brain resting-state functional networks which are significantly perturbed with Alzheimer’s disease.Neuropathological hallmarks of Alzheimer’s disease include loss of neurons, progressive impairments in synaptic function, and deposition of amyloid plaques within the neuropil. Although mice do not readily develop amyloid plaques, our results show Ab 42 deposition was increased in the brain from A. meyeri-treated mice compared with controls, suggesting oral microbiome-induced neuronal responses that have relevance to Alzheimer’s disease neuropathology.Previous studies have suggested that bacteria in the oral cavity were initially taken up by tissue macrophages which may facilitate CNS infection . In the current study, A. meyeri treatment resulted in increased myeloid cell migration and phagocytosis in vitro and elevated macrophage infiltration into the mouse brain in vivo, compared with those of N. elongata treatment.
The cytokines that differed in cannabis users and non-users and in A. meyeri-treated mice and control mice are related to monocyte/macrophage functions. The TNF super family cytokine promoted a compromised blood-brain barrier, and monocytes migrated across the BBB into the brain in response to MCP-1 . Although it is not clear if macrophage infiltration results in CNS abnormalities in the setting of disease-associated immune perturbations, macrophage infiltration into the brain has been demonstrated in the pathogenesis of several diseases.In the current study, A. meyeri administration increased plasma levels of MIP-1a in some mice. However, cannabis smoking altered oral microbiome notlimited to A. meyeri; thus, marijuana grow system the decreased plasma levels of MIP-1a in cannabis users may stem from myeloid cell activation by other bacteria or by reduced total bacterial translocation due to cannabis reduced barrier permeability . In general, bacterial stimulation reduces phagocytosis and promotes proinflammatory cytokine production by myeloid cells. Unexpectedly, A. meyeridid not affect phagocytosis and did not induce prion flammatory cytokines but did increase myeloid cell infiltration and amyloid production in the brain.
It is possible that A. meyeri maybe a new exposure to mice which induces the immune responses and CNS effect. However,there is no evidence on the causal link between a new bacterial exposure in the oral cavity and neuropathology in mice. Thus, we believe that A. meyeri is a unique oral bacterium that is linked to CNS function.We have tested novel object recognition in C57/B6 mice after 6-month exposure to A. meyeri, but did not find significant memory deficits.The reasons for the null finding are as follows: 1) more than 6-month exposure is necessary to see memory changes, 2) the nature of wild type C57/B6 mice, and 3) the age of mice might play an important role with our mice being too young to detect any changes. Todate, there were few to no published studies measuring effects of a specific oral microbial dysbiosis pathobiont on behavior in wildty pemice. In 2018, the study of P. gingivalis found that this pathobiont induces memory impairment in 13-month-old mice and not 2-month-oldmice suggesting an age-related effect, but without enough age cross sections to determine when susceptibility occurred. Thus, we have refined our future strategy to analyze other neurological defects or pathological signs and started to conduct studies that use mice at different ages and include memory-related longitudinal measures, such as the Novel Object Recognition task that focuses on the hippocampus and prefrontal cortex memory functions, the Novel Tactile Recognition task that focuses on the hippocampus and parietal cortex memory functions, and finally the Water radial arm maze that focuses on spatial memory and cognitive flexibility.