Effects of gender and social support on cardiovascular reactivity to a speech task

The effects of gender and social support on cardiovascular reactivity to a speech task were examined in this study. Seventeen males and seventeen females performed a speech task, once in the presence of an experimenter with their significant other present offering encouragement and support and once in the presence of the experimenter alone. Both blood pressure (i.e., systolic (SBP) and diastolic (DBP)) and hemodynamic parameters (i.e., heart rate (HR), cardiac output (converted to cardiac index, CI), stroke volume (converted to stroke index, SI), and pre-ejection period (PEP)) were measured during the speech tasks. In addition, total peripheral resistance (TPR) was calculated to examine the effects of the social support manipulation on the vasculature. Performance of the speech tasks was associated with increased SBP, DBP, and HR responses, as well as increased CI and TPR and decreased PEP. Females exhibited higher HR, SI, and CI and lower PEP and TPR than males during the speech tasks. Males exhibited a greater reduction in SI during both preparatory and speech phases than females. No main or interaction effects for social support were noted. These findings suggest that the presence of a significant other may not be sufficient to attenuate cardiovascular reactivity to a speech task and that other more subtle factors may be important.*.;*This dissertation was funded by grants from the West Virginia University Doctoral Student Research Program and the Department of Psychology Alumni Fund for Graduate and Undergraduate Student Research and Travel

Psychological Benefits of Water Aerobics for Fibromyalgia Patients

Individuals with fibromyalgia, a musculoskeletal syndrome, suffer from potentially debilitating symptoms that include pain, tenderness, and fatigue. Because symptoms of fibromyalgia are difficult for others to see, family members and practitioners may not believe the individual is suffering. The combination of a diagnosis of a debilitating disease and the disbelief of people in one’s life can lead to depression. Exercise has been shown to decrease physical and psychological symptoms in individuals with fibromyalgia. This study looks at the psychological benefit of water aerobics in individuals with fibromyalgia. Significant decreases in pain and depression scores were found at post-test and follow-up, suggesting that water aerobics may help improve physical and psychological well-being

Reversal of Misfolding: Prion Disease Behavioral and Physiological Impairments Recover following Postnatal Neuronal Deletion of the PrP Gene

The prionoses are fatal neurodegenerative diseases caused by a pathogenic protein, PrP scrapie, that derives from misfolding of a normal form, PrPc. These diseases progress through stages. A new study by Mallucci et al. in this issue of Neuron shows that prion disease may be reversed in mice by selective removal of the gene in neurons after early physiological, cognitive, and pathological features have developed

An investigation into the genetic architecture of multiple system atrophy and familial Parkinson's disease

Within the past decade, significant genetic underpinnings of devastating neurological disorders including Parkinson’s disease (PD), Alzheimer’s disease (AD) and Amyotrophic Lateral Sclerosis (ALS) have all been illuminated through advanced genomic technologies. Such discoveries have been facilitated by genome wide association (GWA) studies and next generation sequencing (NGS) investigations in order to identify common variants and rare variants, respectively, which contribute to disease risk. This thesis aims to extend these analyses to an understudied disease, multiple system atrophy (MSA), and to investigate the genetic basis of an apparent cluster of PD cases in Greece. Thus, I plan to accomplish three main goals in my thesis: First, I would like to determine if common variants are associated with MSA risk through heritability analysis and if so, can these be identified through imputation of GWA study data using greater than 900 sporadic MSA cases. While common variants harboring an association with MSA may be either protective or deleterious, any significant findings will yield insight into the pathogenesis of disease. Secondly, I would to identify candidate variants and gene-based variability that are associated with MSA using next generation sequencing in approximately 415 samples, about half of which are pathologically confirmed. Ideally, these will be putative causal variants that will shed light on the molecular mechanisms of disease and potential for therapeutic design in the future. However, it is feasible that such rare variants may modulate risk for MSA development. Because MSA is a rare disease systematic investigation of the genetic basis of this disease has been challenging; the cohorts studied are small and thus lack power. Hence, the goal of this work is to produce rational evidence based candidate genes and variants for validation and replication by the MSA research community. This will be a cardinal step towards our understanding of the genetic basis of this severely debilitating and fatal neurodegenerative disorder. Thirdly, I would like to further explore the genetic architecture of Parkinson’s disease among a large Greek kindred that we believe has maintained a high degree of genetic isolation for the last several centuries. While we have identified several risk factors and causal variants associated with Parkinson’s disease, heritability estimates suggest that other genetic variants remain to be found. By utilizing some of the most advanced technological approaches in genetics, I hope to elucidate a missing piece of the puzzle in the etiology and molecular underpinnings of this devastating disease

The α2-adrenergic receptor agonist, clonidine, reduces alcohol drinking in alcohol-preferring (P) rats

Evidence suggests that noradrenergic signaling may play a role in mediating alcohol-drinking behavior in both rodents and humans. We have investigated this possibility by administering clonidine to alcohol-drinking rats selectively bred for alcohol preference (P line). Clonidine is an α2-adrenergic receptor agonist which, at low doses, inhibits noradrenergic signaling by decreasing norepinephrine release from presynaptic noradrenergic neurons. Adult male P rats were given 24-h access to food and water and scheduled access to a 15% (v/v) alcohol solution for 2 h daily. Rats received intraperitoneal (IP) injections with clonidine (0, 10, 20, 40, or 80 µg/kg body weight [BW], 10–11 rats/treatment group) once/day at 30 min prior to onset of the daily 2-h alcohol access period for 2 consecutive days. Clonidine, in doses of 40 or 80 µg/kg BW, significantly reduced alcohol intake on both days of treatment (p < 0.001). Two weeks later, rats were treated with clonidine for 5 consecutive days and clonidine, in doses of 40 or 80 µg/kg BW, reduced alcohol intake on all 5 treatment days (p < 0.001). Clonidine did not alter water consumption during the daily 2-h free-choice between alcohol and water. In a separate group of male P rats, clonidine (40 µg/kg BW) suppressed intake of a saccharin solution (0.04 g/L). These results are consistent with and complement our previous findings that the α1-adrenergic receptor antagonist, prazosin, decreases voluntary alcohol drinking in alcohol-preferring rats, but suggests that effects of clonidine may not be specific for alcohol. The results suggest that although activation of the noradrenergic system plays an important role in mediating voluntary alcohol drinking, care is needed in selecting which drugs to use to suppress central noradrenergic signaling in order to maximize the selectivity of the drugs for treating alcohol-use disorders

A genome-wide association study in multiple system atrophy

Objective: To identify genetic variants that play a role in the pathogenesis of multiple system atrophy (MSA), we undertook a genome-wide association study (GWAS). Methods: We performed a GWAS with .5 million genotyped and imputed single nucleotide polymorphisms (SNPs) in 918 patients with MSA of European ancestry and 3,864 controls. MSA cases were collected from North American and European centers, one third of which were neuropathologically confirmed. Results: We found no significant loci after stringent multiple testing correction. A number of regions emerged as potentially interesting for follow-up at p , 1 3 1026, including SNPs in the genes FBXO47, ELOVL7, EDN1, and MAPT. Contrary to previous reports, we found no association of the genes SNCA and COQ2 with MSA. Conclusions: We present a GWAS in MSA.We have identified several potentially interesting gene loci, including the MAPT locus, whose significance will have to be evaluated in a larger sample set. Common genetic variation in SNCA and COQ2 does not seem to be associated with MSA. In the future, additional samples of well-characterized patients with MSA will need to be collected to perform a larger MSA GWAS, but this initial study forms the basis for these next steps

Evaluation of an AAV2-Based Rapamycin-Regulated Glial Cell Line-Derived Neurotrophic Factor (GDNF) Expression Vector System

Effective regulation of transgene product in anatomically circumscribed brain tissue is dependent on the pharmacokinetics of the regulating agent, the kinetics of transcriptional activation and degradation of the transgene product. We evaluated rapamycin-regulated AAV2-GDNF expression in the rat brain (striatum). Regulated (a dual-component system: AAV2-FBZhGDNF + AAV2-TF1Nc) and constitutive (CMV-driven) expression vectors were compared. Constitutively active AAV2-GDNF directed stable GDNF expression in a dose-dependent manner and it increased for the first month, thereafter reaching a plateau that was maintained over a further 3 months. For the AAV2-regGDNF, rapamycin was administered in a 3-days on/4-days off cycle. Intraperitoneal, oral, and direct brain delivery (CED) of rapamycin were evaluated. Two cycles of rapamycin at an intraperitoneal dose of 10 mg/kg gave the highest GDNF level (2.75±0.01ng/mg protein). Six cycles at 3 mg/kg resulted in lower GDNF values (1.36±0.3 ng/mg protein). Interestingly, CED of rapamycin into the brain at a very low dose (50 ng) induced GDNF levels comparable to a 6-week intraperitoneal rapamycin cycle. This study demonstrates the effectiveness of rapamycin regulation in the CNS. However, the kinetics of the transgene in brain tissue, the regulator dosing amount and schedule are critical parameters that influence the kinetics of accumulation and zenith of the encoded transgene product