Stress & Myelin
White matter is altered in a variety of mood disorders, including PTSD. Environmental stimuli such as stressors are also known to affect myelination. Our lab investigates the effects of stress on myelination in mood-related brain regions, including the hippocampus, amygdala, and prefrontal cortex. We are also interested in differences in the brain that may contribute to an individual’s susceptibility or resilience to stress-induced anxiety. We are using a rodent model of PTSD to explore such questions. Another important question is whether there are critical time periods during development when stress is especially harmful. For example, the prefrontal cortex is highly plastic and potentially particularly vulnerable to the effects of stress during adolescence. In addition, whether white matter is a contributing factor to these disorders or merely a secondary consequence remains largely unknown. Our lab is using viral techniques to enhance oligodendrogenesis to try to answer this question.
Traumatic Brain Injury
A single traumatic brain injury (TBI) can lead to later appearance of chronic neurological disease that plagues patients for the rest of their lives. One of the most well-known of these secondary diseases is post-traumatic epilepsy (PTE), likely because its symptoms are so salient and devastating. TBI also increases risk for other secondary outcomes, including neurodegenerative diseases (dementia, Alzheimer’s, Parkinson’s, and mild cognitive impairment) and affective disorders (depression and PTSD). Our lab has established rodent models of repetitive mild and moderate close-head TBI to investigate how blood-brain barrier dysfunction may play a causal role or act as an early marker in the development of these deleterious secondary outcomes.
Neurodegenerative diseases feature a confluence of many progressive pathophysiological hallmarks. Among those for Alzheimer’s disease, blood brain barrier dysfunction is observed early in disease progression and may drive several subsequent neurodegenerative cascades. Our lab investigates how blood brain barrier dysfunction contributes to neurodegenerative disease etiology, focusing on mechanisms underlying Alzheimer’s disease pathological lesions, inflammation, and related cognitive and behavioral deficits. We use established transgenic animal lines with pharmacologic intervention to study these mechanisms with the goal to perturb or otherwise interrupt the pathophysiologic cascades. Additionally, we collaborate with the Jagust Lab at Lawrence Berkeley National Laboratory to monitor these relationships in aging human populations.
Aging involves a decline in the healthy function of the neurovascular unit that contributes to a spectrum of pathology from cognitive impairment to epilepsy. However, the causes of the transition from a young-and-healthy to aged-and-dysfunctional brain are not well understood. We are investigating aging-related blood-brain barrier (BBB) deterioration as one of the earliest triggers of neurological aging. Our research shows that BBB dysfunction plays a causal role in age-related pathology by activating an inflammatory cascade that eventually leads to neural pathology. We are currently investigating the mechanistic details by which this aberrant neurovascular signaling contributes to aging-related disease, as well as translating our findings towards the clinical context by investigating the efficacy of novel therapeutic approaches aimed at preventing and reversing BBB disruption.