Teresa M. Evans

Rapamycin Treatment Improves Neuron Viability in an In Vitro Model of Stroke

Ischemic stroke is the leading cause of serious, long-term adult disability and is associated with sensorimotor and cognitive impairments due to neuronal degeneration. Currently, recombinant tissue plasminogen activator (rTPA) is the only FDA-approved medical therapy for treatment of patients with acute ischemic stroke. However, rTPA can only be given within 3 hours of symptom onset, and only 2% of patients are eligible. Therefore, there is an urgent need for novel neuroprotective treatment options for ischemic stroke. An emerging treatment for a diverse range of neurological disorders associated with neurodegeneration is rapamycin, a key modulator of the mammalian target of rapamycin (mTOR) pathway. The mTOR pathway is the primary regulator of the cellular response to nutrient availability, changes in energy status and stress as seen following ischemia and reperfusion. However, rapamycin’s effects on mTORC1 and mTORC2 are poorly understood in neurons. In the current study we show that rapamycin can prevent the activation of both mTORC1 and mTORC2 in cortical neurons and improve cell survival following oxygen glucose deprivation (OGD), an in vitro model of ischemic stroke. This work further supports the investigation of rapamycin as a novel neuroprotectant for ischemic stroke.

Evidence for a mental health crisis in graduate education

With mental illness a growing concern within graduate education, data from a new survey should prompt both academia and policy makers to consider intervention strategies.

The effect of mild traumatic brain injury on peripheral nervous system pathology in wild type mice and the G93A mutant mouse model of motor neuron disease

Traumatic brain injury (TBI) is associated with a risk of neurodegenerative disease. Some suggest a link between TBI and motor neuron disease (MND), including amyotrophic lateral sclerosis (ALS). To investigate the potential mechanisms linking TBI to MND, we measured motor function and neuropathology following mild-TBI in wild-type and a transgenic model of ALS, G93A mutant mice. Mild-TBI did not alter the lifespan of G93A mice or age of onset; however, rotarod performance was impaired in G93A verses wild-type mice. Grip strength was reduced only in G93A mice after mild-TBI. Increased electromyography (EMG) abnormalities and markers of denervation (AchR, Runx1) indicate that mild-TBI may result in peripheral effects that are exaggerated in G93A mice. Markers of inflammation (cell edema, astrogliosis and microgliosis) were detected at 24 and 72h in the brain and spinal cord in wild-type and G93A mice. Levels of F2-isoprostanes, a marker of oxidative stress, were increased in the spinal cord 24h post mild-TBI in wild-type mice but were not affected by TBI in G93A mice. In summary, our data demonstrate that mild-TBI induces inflammation and oxidative stress and negatively impacts muscle denervation and motor performance, suggesting mild-TBI can potentiate motor neuron pathology and influence the development of MND in mice.

Moderate modulation of disease in the G93A model of ALS by the compound 2-(2-hydroxyphenyl)-benzoxazole (HBX)

Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neurological disease characterized by degeneration and death of motor neurons. Aberrant protein aggregation and oxidative stress are implicated in the etiology of ALS; thus preventing propagation of early aggregation events and oxidative damage could be an effective therapy. We tested the effect of dietary supplementation (initiated 40 days of age) with 2-(2-hydroxyphenyl)-benzoxazole (HBX), a compound with metal chelator and anti-aggregation properties, on disease onset, progression and lifespan in the G93A mouse model of ALS. Tests were not sufficiently powerful to detect any change to survival distribution of mice treated with HBX. However, the disease onset was delayed and max lifespan was increased in the treatment group. Additionally, disease progression was moderated as shown by reduced neuromuscular denervation measured by repetitive nerve stimulation. F2-isoprostanes, a marker of oxidative damage, are elevated in skeletal muscle from G93A mice at onset and this increase is prevented in HBX fed G93A mice. Furthermore, HBX treatment reduced mutant SOD1 protein aggregation in whole spinal cord of G93A mice at disease onset. Overall, our data suggests that HBX may be able to improve the degenerative symptoms of ALS through the prevention of oxidative damage and protein aggregation. Further studies are needed to uncover the mechanistic effects of HBX in ameliorating ALS pathology.

A cross-sectional study of the use and effectiveness of the Individual Development Plan among doctoral students

Background: The Individual Development Plan (IDP) was introduced as a tool to aid in career planning for doctoral trainees. Despite the National Institutes of Health and academic institutions creating policies that mandate the use of IDPs, little information exists regarding the use and effectiveness of the career planning tool. Methods: We conducted a multi-institutional, online survey to measure IDP use and effectiveness. The survey was distributed to potential respondents via social media and direct email. IDP survey questions were formatted using a five-point Likert scale (strongly agree, agree, neutral, disagree and strongly disagree). For data analysis purposes, responses were grouped into two categories (agree versus does not agree/disagree). The data were summarized as one-way frequencies and the Pearson chi-square test was used to determine the statistical significance of univariate associations between the survey variables and an outcome measure of the effectiveness of the IDP. Results: Among all respondents, fifty-three percent reported that they are required to complete an IDP while thirty-three percent reported that the tool is helpful to their career development. Further, our data suggests that the IDP is most effective when doctoral students complete the tool with faculty mentors with whom they have a positive relationship. Respondents who are confident about their career plans and who take advantage of career development resources at their institution are also more likely to perceive that the IDP is useful for their career development. Conclusion: Given the nuanced use and effectiveness of the IDP, we call for additional research to characterize the overall use and effectiveness of the IDP and to determine whether there are unintended negative consequences created through the use of the tool. Furthermore, we recommend an enhancement of career development infrastructure that would include mentorship training for faculty in order to provide substantially more career planning support to trainees.