Biology subjects

Cohen, T. J.

Publications and source records attributed to Cohen, T. J..

2 recordsLinked to original sources

bioRxiv2022

Effects of Long-Term Alcohol Consumption on Behavior in the P301S (Line PS19) Tauopathy Mouse Model

Alcohol consumption and misuse remain prevalent public health issues with recent reports of increased heavy consumption in older populations in the United States. Several studies have identified alcohol consumption as a risk factor for developing multiple forms of dementia. The behavioral and psychological symptoms of dementia (BPSD), such as changes in affective behavior (e.g. anxiety), precede and coincide with cognitive decline. While many studies have characterized the intersection of alcohol use and affective behaviors, little is known regarding alcohol consumption and BPSD. This study characterizes the impact of long-term alcohol consumption on various behaviors in the P301S (line PS19) tauopathy mouse model. Male and female P301S and littermate control mice underwent two-bottle choice intermittent access to alcohol for sixteen weeks starting at 12 weeks of age. There were no significant differences in total ethanol consumption between wildtype and P301S mice of the same sex; however, drinking behavior differed among genotypes, and female mice of each genotype drank significantly more ethanol than males of each genotype. Following drinking studies, mice were run through a battery of behavioral tests during a period of forced abstinence, including approach/avoidance assays, social behavior tests, and memory and cognition tests. Across these tests we observed differences between groups due to genotype, alcohol history, and interactions between alcohol exposure and genotype. These differences were not always consistent between the sexes. In total, this study reveals significant alcohol-tauopathy interactions in subsequent behavior, which may have implications for understanding how alcohol may impact BPSD in conditions associated with tauopathy like Alzheimers disease and frontotemporal dementia.

neuroscience↗

bioRxiv2021

Synthetic amyloid beta does not induce a robust transcriptional response in innate immune cell culture systems

Alzheimers disease (AD) is a progressive neurodegenerative disease that impacts nearly 400 million people worldwide. The accumulation of amyloid beta (A{beta}) in the brain has historically been associated with AD, and recent evidence suggests that neuroinflammation plays a central role in its origin and progression. These observations have given rise to the theory that A{beta} is the primary trigger of AD, and induces proinflammatory activation of immune brain cells (i.e. microglia), which culminates in neuronal damage and cognitive decline. In order to test this hypothesis, many in vitro systems have been established to study A{beta}-mediated activation of innate immune cells. Nevertheless, the transcriptional resemblance of these models to the microglia in the AD brain has never been comprehensively studied on a genome-wide scale. To address this, we used bulk RNA-seq to assess the transcriptional differences between in vitro cell types used to model neuroinflammation in AD, including several established, primary and iPSC-derived immune cell lines (macrophages, microglia and astrocytes) and their similarities to primary cells in the AD brain. We then analyzed the transcriptional response of these innate immune cells to synthetic A{beta}. We found that human induced pluripotent stem cell (hIPSC)-derived microglia (IMGL) are the in vitro cell model that best resembles primary microglia. Surprisingly, synthetic A{beta} does not trigger a robust transcriptional response in any of the cellular models analyzed, despite testing a wide variety of A{beta} formulations, concentrations, and treatment conditions. Finally, we found that bacterial LPS and INF{gamma} activate microglia and induce transcriptional changes similar to those observed in disease associated microglia present in the AD brain, suggesting the potential suitability of this model to study AD-related neuroinflammation.

neuroscience↗