Neurosciences Commons^™

Mtor: Alzheimer's Disease Prevention For Apoe4 Carriers, Ai-Ling Lin, D. Allan Butterfield, Arlan Richardson

Sanders-Brown Center on Aging Faculty Publications

No abstract provided.

Can Gait Signatures Provide Quantitative Measures For Aiding Clinical Decision-Making? A Systematic Meta-Analysis Of Gait Variability Behavior In Patients With Parkinson’S Disease, Niklas König Ignasiak

Physical Therapy Faculty Articles and Research

A disturbed, inconsistent walking pattern is a common feature of patients with Parkinson's disease (PwPD). Such extreme variability in both temporal and spatial parameters of gait has been associated with unstable walking and an elevated prevalence of falls. However, despite their ability to discretise healthy from pathological function, normative variability values for key gait parameters are still missing. Furthermore, an understanding of each parameter's response to pathology, as well as the inter-parameter relationships, has received little attention. The aim of this systematic literature review and meta-analysis was therefore to define threshold levels for pathological gait variability as well as to …

N-Acetyl Cysteine May Support Dopamine Neurons In Parkinson's Disease: Preliminary Clinical And Cell Line Data., Daniel A. Monti, George Zabrecky, Daniel Kremens, Tsao-Wei Liang, Nancy A. Wintering, Jingli Cai, Xiatao Wei, Anthony J. Bazzan, Li Zhong, Brendan Bowen, Charles Intenzo, Lorraine Iacovitti, Andrew B. Newberg

Marcus Institute of Integrative Health Faculty Papers

BACKGOUND: The purpose of this study was to assess the biological and clinical effects of n-acetyl-cysteine (NAC) in Parkinson's disease (PD).

METHODS: The overarching goal of this pilot study was to generate additional data about potentially protective properties of NAC in PD, using an in vitro and in vivo approach. In preparation for the clinical study we performed a cell tissue culture study with human embryonic stem cell (hESC)-derived midbrain dopamine (mDA) neurons that were treated with rotenone as a model for PD. The primary outcome in the cell tissue cultures was the number of cells that survived the insult …

Inhibiting The Interaction Between Grp94 And Myocilin To Treat Primary Open-Angle Glaucoma, Andrew Stothert

USF Tampa Graduate Theses and Dissertations

Glaucoma is a neurodegenerative protein misfolding disorder classified by increases in IOP, damage to retinal ganglion cells (RGCs), optic nerve (ON) head damage, and progressive irreversible blindness. Primary open-angle glaucoma (POAG) is the most common form of glaucoma, constituting over 90% of clinical cases. POAG is observed in patients where normal outflow channels, mainly the trabecular meshwork (TM), are exposed at the angle formed by the iris and cornea. However, due to TM cellular dysfunction, aqueous outflow resistance is increased preventing normal circulation of aqueous humor. Recent studies have shown that in 2-4% of POAG cases, increased intracellular levels of …

1st Place Research Paper: The Effectiveness Of Yoga Therapy On An Adult, Post-Stroke Population: A Systematic Review, Baylor E. Hogan

Kevin and Tam Ross Undergraduate Research Prize

Objectives: The objectives of this paper are to (1) give a brief overview of stroke pathophysiology (2) outline yoga as a therapeutic strategy (3) present the current research on yoga rehabilitation for stroke (4) discuss the efficacy of yoga for chronic stroke.

Methods: Relevant terms were searched in PubMed, Web of Science, Academic OneFile, ScienceDirect, and Google Scholar electronic databases. Studies were excluded if they contained pediatric stroke, non-stroke neurological diseases, or subjects with comorbidities. Statistically significant data was extracted for the primary measures of nine trials.

Results: Four studies measured statistically significant outcomes (p<0.05). These included improvements in balance, independence, endurance, trait anxiety, fear of falling, self-efficacy, pain, strength, range of motion (ROM), activity, participation, and quality of life (QoL). Discussion: Lack of statistical significance in post-stroke depression (PSD) measures may be due to inadequate intervention length or a psychosocial cause of depression. Improvements in balance, flexibility, and strength from yoga participation permitted progress in disability and functionality. Finally, overall health-related quality of life (HRQL) is affected by the severity of mental disorders and physical disability. Yoga can have a positive effect in both domains and therefore, may improve HRQL.

Conclusion: …

Carotid Ultrasound Is Not Helpful In Simple Syncope, Nicholus Yee M.D., Shilin Patel M.D., Raymond Gong

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Scott JW, Schwartz AL, Gates JD, Gerhard-Herman M, Havens JM. Choosing wisely for syncope: low-value carotid ultrasound use. J Am Heart Assoc. 2014 Aug 13;3(4). pii: e001063. doi: 10.1161/JAHA.114.001063

Revealing The Quality Of Movement: A Meta-Analysis Review To Quantify The Thresholds To Pathological Variability During Standing And Walking, Niklas König Ignasiak

Physical Therapy Faculty Articles and Research

Neuromotor processes are inherently noisy, which results in variability during movement and fluctu-ations in motor control. Although controversial, low levels of variability are traditionally considered healthy, while increased levels are thought to be pathological. This systematic review and meta-analysisof the literature investigates the thresholds between healthy and pathological task variability.

After examining 13,195 publications, 109 studies were included. Results from over 3000 healthy sub-jects and 2775 patients revealed an overall positive effect size of pathology on variability of 0.59 forwalking and 0.80 for sway. For the coefficient of variation of stride time (ST) and sway area (SA), upperthresholds of 2.6% …

1st Place Contest Entry: The Effectiveness Of Yoga Therapy On An Adult, Post-Stroke Population: A Systematic Review, Baylor E. Hogan

Kevin and Tam Ross Undergraduate Research Prize

This is Baylor Hogan's submission for the 2016 Kevin and Tam Ross Undergraduate Research Prize, which won first place. She wrote about the effects of yoga therapy on the physical and mental wellbeing of stroke patients. You can read the final essay that came out of her research here.

Baylor is a senior at Chapman University, majoring in Kinesiology. Her faculty mentor is Dr. Elizabeth DeBaets.

Gene Expression Profiling In An Alzheimer's Disease Mouse Model, Matthew R. Dalton

Senior Honors Theses

Explaining precisely how Alzheimer’s disease (AD)—the world’s most common form of dementia—materializes in the human brain has proven to be one of the most elusive ends in modern medicine. Progressive memory loss, neurodegeneration, and the presence of abnormal protein aggregates of amyloid-beta (Aβ) and neurofibrillary tangles (NFT) characterize this disease. Genome sequencing provides researchers with the ability to better identify disease-related changes in gene expression, some of which may play a role in the initiation and progression toward the AD-like state. Intimate interactions between tissues have been observed in many diseases, particularly between the brain and blood. This analysis seeks …

Exploring Oculomotor Trends In Collegiate Athletes, Brett Whorley, Julie A. Honaker

UCARE: Research Products

Collaborative efforts to improve athlete safety without significantly hindering the rules of the games aim to develop a novel system to better measure and diagnose concussions. Provided that common signs of concussions include blurred vision, distant gaze, and dizziness, the Dizziness and Balance Disorders Lab at UNL believes that the simple oculomotor exam studied in this project may be applied to this procedure. Within the broader goal to better understand the causes, signs, symptoms, and prognosis of concussions, researchers desired to further investigate the results of this oculomotor test. The aim was to identify and interpret correlations between collegiate athlete …

Oscillatory Neural Responses Evoked By Natural Vestibular Stimuli In Humans, Steven Gale, Mario Prsa, Aaron Schurger, Annietta Gay, Aurore Paillard, Bruno Herbelin, Jean-Philippe Guyot, Christophe Lopez, Olaf Blanke

Psychology Faculty Articles and Research

While there have been numerous studies of the vestibular system in mammals, less is known about the brain mechanisms of vestibular processing in humans. In particular, of the studies that have been carried out in humans over the last 30 years, none has investigated how vestibular stimulation (VS) affects cortical oscillations. Here we recorded high-density electroencephalography (EEG) in healthy human subjects and a group of bilateral vestibular loss patients (BVPs) undergoing transient and constant-velocity passive whole body yaw rotations, focusing our analyses on the modulation of cortical oscillations in response to natural VS. The present approach overcame significant technical challenges …

Molecular Analyses Of Circadian Gene Variants Reveal Sex-Dependent Links Between Depression And Clocks, S-Q Shi, M. J. White, H. M. Borsetti, Julie S. Pendergast, A. Hida, C. M. Ciarleglio, P. A. De Verteuil, A. G. Cadar, C. Cala, D. G. Mcmahon, R. C. Shelton, S. M. Williams, C. H. Johnson

Biology Faculty Publications

An extensive literature links circadian irregularities and/or sleep abnormalities to mood disorders. Despite the strong genetic component underlying many mood disorders, however, previous genetic associations between circadian clock gene variants and major depressive disorder (MDD) have been weak. We applied a combined molecular/functional and genetic association approach to circadian gene polymorphisms in sex-stratified populations of control subjects and case subjects suffering from MDD. This approach identified significant sex-dependent associations of common variants of the circadian clock genes hClock, hPer3 and hNpas2 with major depression and demonstrated functional effects of these polymorphisms on the expression or activity of the hCLOCK …

Role Of Slit2 In Reducing Complications After Surgical Brain Injury, Prativa Sherchan

Loma Linda University Electronic Theses, Dissertations & Projects

Surgical brain injury (SBI) is the inadvertent injury to brain tissue at the perisurgical site which occurs due to neurosurgical maneuvers such as incision, retraction, and electrocoagulation that can result in post-operative complications. Blood brain barrier (BBB) disruption and neuroinflammation are major pathophysiological consequences after neurosurgical injury. Blood brain barrier dysfunction leads to increased influx of water and plasma proteins as well as peripheral immune cell infiltration into the brain parenchyma that further potentiates brain edema and worsens post-operative neurological function. Activated resident immune cells and infiltrated peripheral immune cells release inflammatory mediators and promote oxidative stress and cell death …

Mw151 Inhibited Il-1Β Levels After Traumatic Brain Injury With No Effect On Microglia Physiological Responses, Adam D. Bachstetter, Zhengqiu Zhou, Rachel K. Rowe, Bin Xing, Danielle S. Goulding, Alyssa N. Conley, Pradoldej Sompol, Shelby Meier, Jose F. Abisambra, Jonathan Lifshitz, D. Martin Watterson, Linda J. Van Eldik

Sanders-Brown Center on Aging Faculty Publications

A prevailing neuroinflammation hypothesis is that increased production of proinflammatory cytokines contributes to progressive neuropathology, secondary to the primary damage caused by a traumatic brain injury (TBI). In support of the hypothesis, post-injury interventions that inhibit the proinflammatory cytokine surge can attenuate the progressive pathology. However, other post-injury neuroinflammatory responses are key to endogenous recovery responses. Therefore, it is critical that pharmacological attenuation of detrimental or dysregulated neuroinflammatory processes avoid pan-suppression of inflammation. MW151 is a CNS-penetrant, small molecule experimental therapeutic that restores injury- or disease-induced overproduction of proinflammatory cytokines towards homeostasis without immunosuppression. Post-injury administration of MW151 in a …

Alzheimer's Biomarkers Are Correlated With Brain Connectivity In Older Adults Differentially During Resting And Task States, Yang Jiang, Haiqing Huang, Erin Abner, Lucas S. Broster, Gregory A. Jicha, Frederick A. Schmitt, Richard Kryscio, Anders H. Andersen, David Powell, Linda J. Van Eldik, Brian T. Gold, Peter T. Nelson, Charles D. Smith, Mingzhou Ding

Behavioral Science Faculty Publications

β-amyloid (Aβ) plaques and tau-related neurodegeneration are pathologic hallmarks of Alzheimer’s disease (AD). The utility of AD biomarkers, including those measured in cerebrospinal fluid (CSF), in predicting future AD risk and cognitive decline is still being refined. Here, we explored potential relationships between functional connectivity (FC) patterns within the default-mode network (DMN), age, CSF biomarkers (Aβ₄₂ and pTau₁₈₁), and cognitive status in older adults. Multiple measures of FC were explored, including a novel time series-based measure [total interdependence (TI)]. In our sample of 27 cognitively normal older adults, no significant associations were found between levels of Aβ …

Cannabinoid Receptor Interacting Protein Suppresses Agonist-Driven Cb1 Receptor Internalization And Regulates Receptor Replenishment In An Agonist-Biased Manner, Lawrence C. Blumes, Sandra Leone-Kabler, Deborah J. Luessen, Glenn S. Marrs, Erica Lyons, Caroline E. Bass, Rong Chen, Dana E. Selley, Allyn C. Howlett

Neurology Publications

Cannabinoid receptor interacting protein 1a (CRIP1a) is a CB1 receptor (CB1R) distal C-terminus-associated protein that modulates CB1R signaling via G proteins, and CB1R down-regulation but not desensitization (Blume et al. [2015] Cell Signal., 27, 716-726; Smith et al. [2015] Mol. Pharmacol., 87, 747-765). In this study, we determined the involvement of CRIP1a in CB1R plasma membrane trafficking. To follow the effects of agonists and antagonists on cell surface CB(1)Rs, we utilized the genetically homogeneous cloned neuronal cell line N18TG2, which endogenously expresses both CB1R and CRIP1a, and exhibits a well-characterized endocannabinoid signaling system. We developed stable CRIP1a-over-expressing and CRIP1a-siRNA-silenced knockdown …

Pharmacological Blockade Of The Calcium Plateau Provides Neuroprotection Following Organophosphate Paraoxon Induced Status Epilepticus In Rats, Laxmikant S. Deshpande, Robert E. Blair, Beverly A. Huang, Kristin F. Phillips, Robert J. Delorenzo

Neurology Publications

Organophosphate (OP) compounds which include nerve agents and pesticides are considered chemical threat agents. Currently approved antidotes are crucial in limiting OP mediated acute mortality. However, survivors of lethal OP exposure exhibit delayed neuronal injury and chronic behavioral morbidities. In this study, we investigated neuroprotective capabilities of dantrolene and carisbamate in a rat survival model of paraoxon (POX) induced status epilepticus (SE). Significant elevations in hippocampal calcium levels were observed 48-h post POX SE survival, and treatment with dantrolene (10 mg/kg, i.m.) and carisbamate (90 mg/kg, i.m.) lowered these protracted calcium elevations. POX SE induced delayed neuronal injury …

A Urinary Metabolic Signature For Multiple Sclerosis And Neuromyelitis Optica, Teklab Gebregiworgis, Helle H. Nielsen, Chandirasegara Massilamany, Arunakumar Gangaplara, Jay Reddy, Zsolt Illes, Robert Powers

Jay Reddy Publications

Urine is a metabolite-rich biofluid that reflects the body’s effort to maintain chemical and osmotic homeostasis. Clinical diagnosis routinely relies on urine samples because the collection process is easy and noninvasive. Despite these advantages, urine is an under-investigated source of biomarkers for multiple sclerosis (MS). Nuclear magnetic resonance spectroscopy (NMR) has become a common approach for analyzing urinary metabolites for disease diagnosis and biomarker discovery. For illustration of the potential of urinary metabolites for diagnosing and treating MS patients, and for differentiating between MS and other illnesses, 38 urine samples were collected from healthy controls, MS patients, and neuromyelitis optica-spectrum …

Vitamin D Clinical Relevance In The Recovery From Traumatic Brain Injury Among The Military Population, Yuisa M. Colón

Honors Undergraduate Theses

Background: Traumatic brain injury (TBI) still remains a difficult disorder to treat. TBI has been associated to chronic neuroinflammation and a high risk for neurodegenerative disorders. Since 2001 between ten to twenty percent of all deployed military members have suffered a combat-related TBI. Nearly twenty to thirty percent of those will experience chronic cognitive, behavioral and somatic symptoms after suffering a TBI.
Methods: The objective of this review is to evaluate current literature examining vitamin D as a neurosteroid with protective properties and its clinical relevance after traumatic brain injury. Vitamin D is known to participate in neurobiological …

Bisphenol-A And Sleep Adequacy Among Adults In The National Health And Nutrition Examination Surveys, Hind A. Beydoun, May A. Beydoun, Hueiwang Anna Jeng, Alan B. Zonderman, Shaker M. Eid

Community & Environmental Health Faculty Publications

Study Objectives: To evaluate bisphenol-A (BPA) level and its relationship to sleep adequacy in a nationally representative sample of U.S. adults.
Methods: A population-based cross-sectional study was conducted using 2005-2010 National Health and Nutrition Examination Survey whereby data were collected using in-person interviews, physical examination and laboratory testing. BPA level was measured in urine samples and analyzed as loge-transformed variable and in quartiles (< 0.9 ng/mL; 0.9 to < 1.9 ng/mL; 1.9 to < 3.7 ng/mL; 3.7+ ng/mL). Sleep adequacy was operationalized with three questions: "How much sleep do you usually get at night on weekdays or workdays?", "Have you ever told a doctor or other health professionals that you have trouble sleeping?" and "Have you ever been told by a doctor or other health professional that you have a sleep disorder?" Sleep duration was further categorized as (< 6 h, ≥ 6 h); (< 7 h, 7-8 h, > 8 h); (< 5 h, 5-6 h, 7-8 h, ≥ 9 h). Linear, binary, and ordinal logistic regression models were constructed.
Results: Loge-transformed BPA level was inversely related to sleep duration defined, in hours, as a continuous variable, a dichotomous variable (≥ 6, < 6), or an ordinal variable (≥ 9, 7-8, 5-6, < 5), after adjustment for confounders. Help-seeking behavior for sleep problems and diagnosis with sleep disorders were not significantly associated with loge-transformed BPA level in fully adjusted models.
Conclusions: Loge-transformed BPA level may be associated with fewer hours of …

Cerebrovascular Risk Factors, Arteriolar Sclerosis, And Cognitive Decline In The Kentucky Appalachian “Stroke-Belt”, Omar M. Al-Janabi

Theses and Dissertations--Medical Sciences

The relationship between cerebrovascular disease (CVD) risk factors and cognitive impairment or dementia has been widely studied with significant variability in findings between groups. We hypothesized that chronic small vessel injury in the form of arteriolar sclerosis, measured quantitatively using MRI to measure total white matter hyperintensity (WMH) volumes, would identify specific association of CVD risk factors and patterns of cognitive decline, associated with mild cognitive impairment of the cerebrovascular type, that represent the core features of vascular cognitive impairment in our cohort.

A Cross-sectional analysis of clinical and quantitative MRI data on 114 subjects with normal cognitive function (n=52) …

Finding Chemopreventatives To Reduce Amyloid Beta In Yeast, Ian Macreadie, Costa Arvanitis, Prashant Bharadwaj

Research outputs 2014 to 2021

Alzheimer's disease (AD) is the most common form of age-related dementia with the latest report (WorldAlzheimerReport, 2015) showing 46.8 million people are currently affected by dementia. That number is expected to double every 20 years unless there is effective therapeutic intervention.

Post-Stroke Depression Among Stroke Survivors Attending Two Hospitals In Kampala Uganda, Martha Sajatovic, Kathyleen Smyth

Faculty Scholarship

Background: The burden of stroke worldwide is increasing rapidly. There is paucity of data on post-stroke depression (PSD) among stroke survivors in Uganda, despite the high prevalence of PSD reported elsewhere. Methods: In a cross-sectional study, we assessed adult participants with confirmed first stroke with a standardized questionnaire. The Patient Health Questionnaire-9 was used to assess for depression among non-aphasic patients while the Aphasic Depression Rating Scale was administered to aphasic patients. Univariable and multivariable analyses performed to describe associations with PSD. Results: Forty three females (58.9%) and 30 males (41.1%) who had a stroke participated. Fifty eight (79.5%) had …

Loss Of Vglut3 Produces Circadian-Dependent Hyperdopaminergia And Ameliorates Motor Dysfunction And L-Dopa-Mediated Dyskinesias In A Model Of Parkinson's Disease., Christopher B. Divito, Kathy Steece-Collier, Daniel T. Case, Sean-Paul G. Williams, Jennifer A. Stancati, Lianteng Zhi, Maria E. Rubio, Caryl E. Sortwell, Timothy J. Collier, David Sulzer, Robert H. Edwards, Hui Zhang, Rebecca P. Seal

Department of Neuroscience Faculty Papers

UNLABELLED: The striatum is essential for many aspects of mammalian behavior, including motivation and movement, and is dysfunctional in motor disorders such as Parkinson's disease. The vesicular glutamate transporter 3 (VGLUT3) is expressed by striatal cholinergic interneurons (CINs) and is thus well positioned to regulate dopamine (DA) signaling and locomotor activity, a canonical measure of basal ganglia output. We now report that VGLUT3 knock-out (KO) mice show circadian-dependent hyperlocomotor activity that is restricted to the waking cycle and is due to an increase in striatal DA synthesis, packaging, and release. Using a conditional VGLUT3 KO mouse, we show that deletion …

Rewiring The Brain For Happiness: The Neuroscience Of Happiness, Part 2, Kevin Corcoran

University Faculty Publications and Creative Works

No abstract provided.

Abcc9/Sur2 In The Brain: Implications For Hippocampal Sclerosis Of Aging And A Potential Therapeutic Target, Peter T. Nelson, Gregory A. Jicha, Wang-Xia Wang, Eseosa T. Ighodaro, Sergey C. Artiushin, Colin G. Nichols, David W. Fardo

Sanders-Brown Center on Aging Faculty Publications

The ABCC9 gene and its polypeptide product, SUR2, are increasingly implicated in human neurologic disease, including prevalent diseases of the aged brain. SUR2 proteins are a component of the ATP-sensitive potassium (“K _ATP ”) channel, a metabolic sensor for stress and/or hypoxia that has been shown to change in aging. The K _ATP channel also helps regulate the neurovascular unit. Most brain cell types express SUR2, including neurons, astrocytes, oligodendrocytes, microglia, vascular smooth muscle, pericytes, and endothelial cells. Thus it is not surprising that ABCC9 gene variants are associated with risk for human brain diseases. For example, Cantu syndrome is …

Initial Validation Of A Novel Method Of Presurgical Language Localization Through Functional Connectivity (Fcmri), Stephanie M. Noble, Dustin Scheinost, Susan Y. Bookheimer, Patricia Walshaw, R Todd Constable, Christopher F. Benjamin

Yale Day of Data

OBJECTIVE: Neurosurgery is potentially curative in chronic epilepsy but can only be offered to patients if the surgical risk to language is known. Clinical functional magnetic resonance imaging (fMRI) is an ideal, noninvasive method for localizing language cortex yet remains to be validated for this purpose. We have recently presented a novel method for localizing language cortex. Here we present a preliminary evaluation of this method’s validity. We hypothesized language regions identified using this novel method would demonstrate stronger functional connectivity than randomly generated set of proximal networks. METHOD: fMRI data were collected from sixteen temporal lobe patients …

Novel Human Abcc9/Sur2 Brain-Expressed Transcripts And An Eqtl Relevant To Hippocampal Sclerosis Of Aging, Peter T. Nelson, Wang-Xia Wang, Bernard R. Wilfred, Angela Wei, James Dimayuga, Qingwei Huang, Eseosa T. Ighodaro, Sergey C. Artiushin, David W. Fardo

Sanders-Brown Center on Aging Faculty Publications

ABCC9 genetic polymorphisms are associated with increased risk for various human diseases including hippocampal sclerosis of aging. The main goals of this study were 1 > to detect the ABCC9 variants and define the specific 3′ untranslated region (3′UTR) for each variant in human brain, and 2 > to determine whether a polymorphism (rs704180) associated with risk for hippocampal sclerosis of aging pathology is also associated with variation in ABCC9 transcript expression and/or splicing. Rapid amplification of ABCC9 cDNA ends (3′RACE) provided evidence of novel 3′ UTR portions of ABCC9 in human brain. In silico and experimental studies were performed focusing on …

Toll-Like Receptors And Dectin-1, A C-Type Lectin Receptor, Trigger Divergent Functions In Cns Macrophages, John C. Gensel, Yan Wang, Zhen Guan, Kyle A. Beckwith, Kaitlyn J. Braun, Ping Wei, Dana M. Mctigue, Phillip G. Popovich

Spinal Cord and Brain Injury Research Center Faculty Publications

Spinal cord injury (SCI) activates macrophages, endowing them with both reparative and pathological functions. The mechanisms responsible for these divergent functions are unknown but are likely controlled through stochastic activation of different macrophage receptor subtypes. Various danger-associated molecular patterns released from dying cells in the injured spinal cord likely activate distinct subtypes of macrophage pattern recognition receptors, including bacterial toll-like receptors (TLRs) and fungal C-type lectin receptors (e.g., dectin-1). To determine the in vivo consequences of activating these receptors, ligands specific for TLR2 or dectin-1 were microinjected, alone or in combination, into intact spinal cord. Both ligands elicit a florid …

Taranis Functions With Cyclin A And Cdk1 In A Novel Arousal Center To Control Sleep In Drosophila., Dinis J.S. Afonso, Die Liu, Daniel R. Machado, Huihui Pan, James E.C. Jepson, Dragana Rogulja, Kyunghee Koh

Department of Neuroscience Faculty Papers

Sleep is an essential and conserved behavior whose regulation at the molecular and anatomical level remains to be elucidated. Here, we identify TARANIS (TARA), a Drosophila homolog of the Trip-Br (SERTAD) family of transcriptional coregulators, as a molecule that is required for normal sleep patterns. Through a forward-genetic screen, we isolated tara as a novel sleep gene associated with a marked reduction in sleep amount. Targeted knockdown of tara suggests that it functions in cholinergic neurons to promote sleep. tara encodes a conserved cell-cycle protein that contains a Cyclin A (CycA)-binding homology domain. TARA regulates CycA protein levels and genetically …