The Reality of Bipolar Disorder: A Dance Film to Bring Awareness to the Misconceptions of Mental Health

For my project, I researched bipolar disorder to create a dance film highlighting the associated symptoms and emotions of hypomanic and depressive episodes. The purpose of this research is to bring awareness to and educate on the reality of these mental health symptoms to reduce mental health stereotypes and stigma. I researched academic texts and peer-reviewed articles about bipolar disorder written from the perspective of those diagnosed with it and used the symptom criteria in the Diagnostic and Statistical Manual of Mental Disorders to compose, choreograph, film, and edit my dance film. The completed film showcases what daily life could look and feel like to those with the disorder. The film highlights pedestrian activities and symptomatic behaviors as well as the internal thoughts and emotions expressed through modern dance choreography. This film was presented in two Western Kentucky University Dance Program student choreography shows; Last Chance to Dance and The Dance Project. This dance film will also be uploaded on the internet for public access, creating a research archive and allowing the message to spread beyond its initial release

TRPV4 disrupts mitochondrial transport and causes axonal degeneration via a CaMKII-dependent elevation of intracellular Ca(2)

The cation channel transient receptor potential vanilloid 4 (TRPV4) is one of the few identified ion channels that can directly cause inherited neurodegeneration syndromes, but the molecular mechanisms are unknown. Here, we show that in vivo expression of a neuropathy-causing TRPV4 mutant (TRPV4(R269C)) causes dose-dependent neuronal dysfunction and axonal degeneration, which are rescued by genetic or pharmacological blockade of TRPV4 channel activity. TRPV4(R269C) triggers increased intracellular Ca(2+) through a Ca(2+)/calmodulin-dependent protein kinase II (CaMKII)-mediated mechanism, and CaMKII inhibition prevents both increased intracellular Ca(2+) and neurotoxicity in Drosophila and cultured primary mouse neurons. Importantly, TRPV4 activity impairs axonal mitochondrial transport, and TRPV4-mediated neurotoxicity is modulated by the Ca(2+)-binding mitochondrial GTPase Miro. Our data highlight an integral role for CaMKII in neuronal TRPV4-associated Ca(2+) responses, the importance of tightly regulated Ca(2+) dynamics for mitochondrial axonal transport, and the therapeutic promise of TRPV4 antagonists for patients with TRPV4-related neurodegenerative diseases

Hyperhomocysteinemia-Induced Gene Expression Changes in the Cell Types of the Brain

High plasma levels of homocysteine, termed hyperhomocysteinemia, are a risk factor for vascular cognitive impairment and dementia, which is the second leading cause of dementia. While hyperhomocysteinemia induces microhemorrhages and cognitive decline in mice, the specific effect of hyperhomocysteinemia on each cell type remains unknown. We took separate cultures of astrocytes, microglia, endothelial cells, and neuronal cells and treated each with moderate levels of homocysteine for 24, 48, 72, and 96 hr. We then determined the gene expression changes for cell-specific markers and neuroinflammatory markers including the matrix metalloproteinase 9 system. Astrocytes had decreased levels of several astrocytic end feet genes, such as aquaporin 4 and an adenosine triphosphate (ATP)-sensitive inward rectifier potassium channel at 72 hr, as well as an increase in matrix metalloproteinase 9 at 48 hr. Gene changes in microglia indicated a peak in proinflammatory markers at 48 hr followed by a peak in the anti-inflammatory marker, interleukin 1 receptor antagonist, at 72 hr. Endothelial cells had reduced occludin expression at 72 hr, while kinases and phosphatases known to alter tau phosphorylation states were increased in neuronal cells. This suggests that hyperhomocysteinemia induces early proinflammatory changes in microglia and astrocytic changes relevant to their interaction with the vasculature. Overall, the data show how hyperhomocysteinemia could impact Alzheimer’s disease and vascular cognitive impairment and dementia

Therapeutic Trem2 Activation Ameliorates Amyloid-Beta Deposition and Improves Cognition in the 5XFAD Model of Amyloid Deposition

BACKGROUND: Triggering receptor expressed on myeloid cell-2 (TREM2) is a lipid and lipoprotein binding receptor expressed by cells of myeloid origin. Homozygous TREM2 mutations cause early onset progressive presenile dementia while heterozygous, point mutations triple the risk of Alzheimer\u27s disease (AD). Although human genetic findings support the notion that loss of TREM2 function exacerbates neurodegeneration, it is not clear whether activation of TREM2 in a disease state would result in therapeutic benefits. To determine the viability of TREM2 activation as a therapeutic strategy, we sought to characterize an agonistic Trem2 antibody (AL002a) and test its efficacy and mechanism of action in an aggressive mouse model of amyloid deposition. METHODS: To determine whether agonism of Trem2 results in therapeutic benefits, we designed both intracranial and systemic administration studies. 5XFAD mice in the intracranial administration study were assigned to one of two injection groups: AL002a, a Trem2-agonizing antibody, or MOPC, an isotype-matched control antibody. Mice were then subject to a single bilateral intracranial injection into the frontal cortex and hippocampus and euthanized 72 h later. The tissue from the left hemisphere was histologically examined for amyloid-beta and microglia activation, whereas the tissue from the right hemisphere was used for biochemical analyses. Similarly, mice in the systemic administration study were randomized to one of the aforementioned injection groups and the assigned antibody was administered intraperitoneally once a week for 14 weeks. Mice underwent behavioral assessment between the 12- and 14-week timepoints and were euthanized 24 h after their final injection. The tissue from the left hemisphere was used for histological analyses whereas the tissue from the right hemisphere was used for biochemical analyses. RESULTS: Here, we show that chronic activation of Trem2, in the 5XFAD mouse model of amyloid deposition, leads to reversal of the amyloid-associated gene expression signature, recruitment of microglia to plaques, decreased amyloid deposition, and improvement in spatial learning and novel object recognition memory. CONCLUSIONS: These findings indicate that Trem2 activators may be effective for the treatment of AD and possibly other neurodegenerative disorders

Evaluation of Responses to Vaccination of Angus Cattle for Four Viruses that Contribute to Bovine Respiratory Disease Complex

Initial antibody titers are maternally-derived from colostrum, then decay with age. Change in antibody titer levels were compared between four viruses contributing to the Bovine Respiratory Disease Complex (BRDC), and evaluation of response to vaccination indicated that antibody production will not occur when high levels of maternal antibodies are present. The maternal antibodies were found to decay with calf age for each of the four viruses, which allowed for the estimation of a maximum circulating titer level under which a positive antibody response to vaccination could occur. Phenotypic correlations were calculated between the antibody titers for the four viruses across multiple time points. Results indicate a difference in the response to vaccination between the four virus antigen