Life Sciences Commons^™

Lights And Larvae: Using Optogenetics To Teach Recombinant Dna And Neurobiology, John Titlow, Heidi Anderson, Robin L. Cooper

Biology Faculty Publications

Switching genes between organisms and controlling an animal’s brain using lasers may seem like science fiction, but with advancements in a technique called optogenetics, such experiments are now common in neuroscience research. Optogenetics combines recombinant DNA technology with a controlled light source to help researchers address biomedical questions in the life sciences. The technique has gained the most traction in neurobiology—the biology of the nervous system—where specific wavelengths of light are used to control or measure the activity of neurons in transgenic organisms (i.e., those with artificially inserted genes).

These optical recording and stimulation techniques are used in nervous system …

Neuroinflammation And Neurodegeneration In Adult Rat Brain From Binge Ethanol Exposure: Abrogation By Docosahexaenoic Acid, Nuzhath Tajuddin, Kwan-Hoon Moon, Simon Alex Marshall, Kimberly Nixon, Edward J. Neafsey, Hee-Yong Kim, Michael A. Collins

Pharmaceutical Sciences Faculty Publications

Evidence that brain edema and aquaporin-4 (AQP4) water channels have roles in experimental binge ethanol-induced neurodegeneration has stimulated interest in swelling/edema-linked neuroinflammatory pathways leading to oxidative stress. We report here that neurotoxic binge ethanol exposure produces comparable significant effects in vivo and in vitro on adult rat brain levels of AQP4 as well as neuroinflammation-linked enzymes: key phospholipase A2 (PLA2) family members and poly (ADP-ribose) polymerase-1 (PARP-1). In adult male rats, repetitive ethanol intoxication (3 gavages/d for 4 d, ∼ 9 g/kg/d, achieving blood ethanol levels ∼ 375 mg/dl; "Majchrowicz" model) significantly increased AQP4, Ca+2-dependent PLA2 GIVA (cPLA2), phospho-cPLA2 GIVA …

Self-Reported Head Injury And Risk Of Late-Life Impairment And Ad Pathology In An Ad Center Cohort, Erin L. Abner, Peter T. Nelson, Frederick A. Schmitt, Steven R. Browning, David W. Fardo, Lijie Wan, Gregory A. Jicha, Gregory E. Cooper, Charles D. Smith, Allison M. Caban-Holt, Linda J. Van Eldik, Richard J. Kryscio

Sanders-Brown Center on Aging Faculty Publications

Aims: To evaluate the relationship between self-reported head injury and cognitive impairment, dementia, mortality, and Alzheimer's disease (AD)-type pathological changes. Methods: Clinical and neuropathological data from participants enrolled in a longitudinal study of aging and cognition (n = 649) were analyzed to assess the chronic effects of self-reported head injury. Results: The effect of self-reported head injury on the clinical state depended on the age at assessment: for a 1-year increase in age, the OR for the transition to clinical mild cognitive impairment (MCI) at the next visit for participants with a history of head injury was 1.21 and 1.34 …

Flavonoids With Novel Nicotinic Activity As Potential Pharmacotherapies To Treat Ethanol-Induced Neurotoxicity, Joseph A. Lutz

Theses and Dissertations--Pharmacy

Ethanol causes neurotoxicity via several mechanisms at different points in the cycle of dependence, including neuroinflammation and oxidative stress during ethanol exposure as well as excitotoxicity during ethanol withdrawal. The primary therapeutic implication is that ethanol-induced neurotoxicity requires multifunctional pharmacotherapies which reduce all mechanisms. Using an innovative pharmacological high throughput screening method on a large plant extract library we discovered flavonoids with alpha7 nicotinic acetylcholine receptor (nAChR) activity. In addition to their well-known anti-inflammatory and antioxidant properties, this novel activity means they can potentially reduce excitotoxicity and therefore makes them ideal for inhibition of ethanol-induced neurotoxicity. Rhamnetin, the candidate compound, …

Leptin Resistance Induced Obesity And Diabetes Promote Neuropathological Changes In The Aging Brain, Thomas Platt

Theses and Dissertations--Molecular and Cellular Biochemistry

The aging brain is prone to the development of pathology and dementia. With a rapidly growing elderly population diagnoses of neurodegenerative diseases, such as Alzheimer’s disease (AD), frontotemporal dementia (FTD), and Parkinson’s disease are on the rise. Additionally, diabetes and obesity are linked to an increased risk of dementia. The convergence of this increasingly aged population with the obesity and diabetes epidemic give rise to new concerns regarding the future of prevention and treatment of neurodegenerative diseases. Our lab has previously shown that leptin, an adipokine involved in signaling satiety to the hypothalamus, can modulate the generation of the amyloid …

Immunotherapy In Combination With Behavioral Enrichment In A Canine Model Of Aging, Paulina R. Davis

Theses and Dissertations--Pharmacology and Nutritional Sciences

Alzheimer’s disease (AD) is characterized by cognitive decline and hallmark neuropathology, including β-amyloid (Aβ). Therapeutic strategies for AD are focusing on reducing Aβ. Canines develop Aβ neuropathology and cognitive decline with age similar to AD patients. In previous studies, immunization with Aβ1-42 (VAC) in aged canines decreased brain Aβ but did not improve cognition. Behavioral enrichment (ENR) improved cognition without reducing brain Aβ. We hypothesized that VAC combined with ENR would provide cognitive benefits and reduce Aβ neuropathology, as compared individual VAC and ENR treatments. Aged beagles were placed into groups: control, VAC with fibrillar Aβ1-42, ENR, and combination treatment …

Dopaminergic And Activity-Dependent Modulation Of Mechanosensory Responses In Drosophila Melanogaster Larvae, Josh S. Titlow

Theses and Dissertations--Biology

A central theme of this dissertation is nervous system plasticity. Activity-dependent plasticity and dopaminergic modulation are two processes by which neural circuits adapt their function to developmental and environmental changes. These processes are involved in basic cognitive functions and can contribute to neurological disorder. An important goal in modern neurobiology is understanding how genotypic variation influences plasticity, and leveraging the quantitative genetics resources in model organisms is a valuable component of this endeavor. To this end I investigated activity-dependent plasticity and dopaminergic modulation in Drosophila melanogaster larvae using neurobiological and genetic approaches.

Larval mechanosensory behavior is described in Chapter 2. …

Calpain 5: A Non-Classical Calpain Highly Expressed In The Cns And Localized To Mitochondria And Nuclear Pml Bodies, Ranjana Singh

Theses and Dissertations--Neuroscience

Calpain 5 (CAPN5) is a non-classical member of the calpain family. It lacks the EF-hand motif characteristic of the classical calpains, calpain 1 and 2, but retains catalytic and Ca²⁺ binding non EF domains. Tra-3, an ortholog of CAPN5, is involved in necrotic cell death in C.elegans; although specific role of CAPN5 has not been investigated in the mammalian CNS. I compared relative mRNA levels of calpains in rat CNS, which revealed that CAPN5 is the second most highly expressed calpain. We examined relative levels of CAPN5 from late embryonic day 18 to postnatal day 90 and …