Honors & Awards
Postdoctoral Fellowship, American Heart Assosciation (2018-2020)
Ph.D., University of Massachusetts Boston, Developmental & Brain Sciences (2017)
M.A., Humboldt State University, Biological Psychology (2011)
B.A., Humboldt State University, Psychology (2009)
- Pre-treatment with microRNA-181a Antagomir Prevents Loss of Parvalbumin Expression and Preserves Novel Object Recognition Following Mild Traumatic Brain Injury NEUROMOLECULAR MEDICINE 2019; 21 (2): 170–81
Hippocampal sub-regional differences in the microRNA response to forebrain ischemia.
Molecular and cellular neurosciences
Transient forebrain ischemia, as occurs with cardiac arrest and resuscitation, results in impaired cognitive function secondary to delayed neuronal cell death in hippocampal cornu ammonis-1 (CA1). Comparatively, hippocampal neurons in the adjacent dentate gyrus (DG) survive, suggesting that elucidating the molecular mechanisms underpinning hippocampal sub-regional differences in ischemic tolerance could be central in the development of novel interventions to improve outcome in survivors of forebrain ischemia. MicroRNAs (miRNAs) are non-coding RNAs that modulate the translation of target genes and have been established as an effective therapeutic target for other models of injury. The objective of the present study was to assess and compare post-injury miRNA profiles between CA1 and DG using a rat model of forebrain ischemia. CA1 and DG sub-regions were dissected from rat hippocampi following 10 min of forebrain ischemia at three time points (3 h, 24 h, and 72 h) and at baseline. Pronounced differences between CA1 and DG were observed for several select miRNAs, including miR-181a-5p, a known regulator of cerebral ischemic injury. We complexed fluorescent in situ hybridization with immunohistochemistry to observe cell-type specific and temporal differences in mir-181a-5p expression between CA1 and DG in response to injury. Using established miRNA-mRNA prediction algorithms, we extended our observations in CA1 miRNA dysregulation to identify key functional pathways as potential modulators of CA1 ischemic vulnerability. In summary, our observations support a central role for miRNAs in selective CA1 ischemic vulnerability and suggest that cell-specific miRNA targeting could be a viable clinical approach to preserve CA1 neurons and improve cognitive outcomes for survivors of transient forebrain ischemia.
View details for DOI 10.1016/j.mcn.2019.05.003
View details for PubMedID 31128240
- Age-dependent sexual dimorphism in hippocampal cornu ammonis-1 perineuronal net expression in rats BRAIN AND BEHAVIOR 2019; 9 (5)
Neurosurgical anesthesia for a pregnant woman with macroprolactinoma A case report
2018; 97 (37): e12360
Being required to perform neurosurgery on a pregnant woman is rare, but occasionally unavoidable. In these cases, clinical anesthesiologists are confronted with conflicting information and few evidence-based guidelines.Here, we describe the successful anesthetic management of a 24-week pregnant woman with macroprolactinoma who underwent endonasal transsphenoidal resection of pituitary adenoma.According to the prolactin (PRL) level and magnetic resonance imaging (MRI) results, the patient was diagnosed with macroprolactinoma and kept stable after taking the regular bromocriptine treatment. However, after stopping the drug by herself because of pregnancy, her tumor increased in size and she suffered from vision loss. Surgery was recommended as soon as possible to lessen the compression in the eye. However, the anesthetic management was a considerable risk due to the increased chance of maternal mortality, intrauterine growth restriction, or preterm labor.We held a multidisciplinary meeting before the operation and made a detailed plan for how to proceed. During the operation, our team ensured intensive monitoring, provided adequate oxygen, and achieved haemodynamic stability. Anesthetics like sufentanyl, rocuronium, propofol, and desflurane were carefully chosen in order to ensure the safety of both the mother and fetus.Under the careful and successful anesthetic management, the pregnant woman underwent the surgery smoothly and neither the mother nor baby experienced any pre- or postoperative complications. At the 38th week of gestation, the patient received a cesarean section and the baby had developed normally.Neurosurgeries in pregnancy are sparse, and careful planning with cross-disciplinary specialists was needed in advance of the operation. Moreover, when dealing with such surgeries, we should consider the safety of both the mother and fetus, which is challenging but important.
View details for PubMedID 30212994
View details for PubMedCentralID PMC6156042
Profiling the Post-Injury Hippocampal MicroRNA Response to Transient Forebrain Ischemia: Sub-regional Differences Between Cornu Ammonis-1 and Dentate Gyrus
FEDERATION AMER SOC EXP BIOL. 2018
View details for Web of Science ID 000436986703455
Stress and corticosteroids regulate rat hippocampal mitochondrial DNA gene expression via the glucocorticoid receptor
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
2016; 113 (32): 9099-9104
Glucocorticoids (GCs) are involved in stress and circadian regulation, and produce many actions via the GC receptor (GR), which is classically understood to function as a nuclear transcription factor. However, the nuclear genome is not the only genome in eukaryotic cells. The mitochondria also contain a small circular genome, the mitochondrial DNA (mtDNA), that encodes 13 polypeptides. Recent work has established that, in the brain and other systems, the GR is translocated from the cytosol to the mitochondria and that stress and corticosteroids have a direct influence on mtDNA transcription and mitochondrial physiology. To determine if stress affects mitochondrially transcribed mRNA (mtRNA) expression, we exposed adult male rats to both acute and chronic immobilization stress and examined mtRNA expression using quantitative RT-PCR. We found that acute stress had a main effect on mtRNA expression and that expression of NADH dehydrogenase 1, 3, and 6 (ND-1, ND-3, ND-6) and ATP synthase 6 (ATP-6) genes was significantly down-regulated. Chronic stress induced a significant up-regulation of ND-6 expression. Adrenalectomy abolished acute stress-induced mtRNA regulation, demonstrating GC dependence. ChIP sequencing of GR showed that corticosterone treatment induced a dose-dependent association of the GR with the control region of the mitochondrial genome. These findings demonstrate GR and stress-dependent transcriptional regulation of the mitochondrial genome in vivo and are consistent with previous work linking stress and GCs with changes in the function of brain mitochondria.
View details for DOI 10.1073/pnas.1602185113
View details for Web of Science ID 000381293300069
View details for PubMedID 27457949
View details for PubMedCentralID PMC4987818
NEUROEPIGENETICS OF STRESS
2014; 275: 420-435
Stress, a common if unpredictable life event, can have pronounced effects on physiology and behavior. Individuals show wide variation in stress susceptibility and resilience, which are only partially explained by variations in coding genes. Developmental programing of the hypothalamic-pituitary-adrenal stress axis provides part of the explanation for this variance. Epigenetic approaches have successfully helped fill the explanatory gaps between the influences of gene and environment on stress responsiveness, and differences in the sequelae of stress across individuals and generations. Stress and the stress axis interacts bi-directionally with epigenetic marks within the brain. It is now clear that exposure to stress, particularly in early life, has both acute and lasting effects on these marks. They in turn influence cognitive function and behavior, as well as the risk for suicide and psychiatric disorders across the lifespan and, in some cases, unto future generations.
View details for DOI 10.1016/j.neuroscience.2014.06.041
View details for Web of Science ID 000340083500038
View details for PubMedID 24976514
A zebrafish model of glucocorticoid resistance shows serotonergic modulation of the stress response
FRONTIERS IN BEHAVIORAL NEUROSCIENCE
One function of glucocorticoids is to restore homeostasis after an acute stress response by providing negative feedback to stress circuits in the brain. Loss of this negative feedback leads to elevated physiological stress and may contribute to depression, anxiety, and post-traumatic stress disorder. We investigated the early, developmental effects of glucocorticoid signaling deficits on stress physiology and related behaviors using a mutant zebrafish, gr(s357), with non-functional glucocorticoid receptors (GRs). These mutants are morphologically inconspicuous and adult-viable. A previous study of adult gr(s357) mutants showed loss of glucocorticoid-mediated negative feedback and elevated physiological and behavioral stress markers. Already at 5 days post-fertilization, mutant larvae had elevated whole body cortisol, increased expression of pro-opiomelanocortin (POMC), the precursor of adrenocorticotropic hormone (ACTH), and failed to show normal suppression of stress markers after dexamethasone treatment. Mutant larvae had larger auditory-evoked startle responses compared to wildtype sibling controls (gr(wt)), despite having lower spontaneous activity levels. Fluoxetine (Prozac) treatment in mutants decreased startle responding and increased spontaneous activity, making them behaviorally similar to wildtype. This result mirrors known effects of selective serotonin reuptake inhibitors (SSRIs) in modifying glucocorticoid signaling and alleviating stress disorders in human patients. Our results suggest that larval gr(s357) zebrafish can be used to study behavioral, physiological, and molecular aspects of stress disorders. Most importantly, interactions between glucocorticoid and serotonin signaling appear to be highly conserved among vertebrates, suggesting deep homologies at the neural circuit level and opening up new avenues for research into psychiatric conditions.
View details for DOI 10.3389/fnbeh.2012.00068
View details for Web of Science ID 000310727400002
View details for PubMedID 23087630
View details for PubMedCentralID PMC3468897