View All Items
(1 - 2 of 2)
- Title
- ELECTROCONVULSIVE SHOCK AMELIORATES DISEASE PROCESSES AND EXTENDS SURVIVAL IN HUNTINGTON MUTANT MICE.
- Creator
-
Baharani, Akanksha, Chan, Sic L., University of Central Florida
- Abstract / Description
-
ABSTRACT Huntington's disease (HD) is a devastating autosomal dominantly inherited neurological disorder caused by an abnormal expansion of CAG trinucleotide repeats in the gene coding for the N-terminal region of the huntingtin (Htt) protein, which leads to the formation of a polyglutamine stretch. The greater the CAG repeats, the earlier the onset of the disease. The polyglutamine stretch destabilizes the Htt protein leading to misfolding, abnormal processing, aggregation, and inclusion...
Show moreABSTRACT Huntington's disease (HD) is a devastating autosomal dominantly inherited neurological disorder caused by an abnormal expansion of CAG trinucleotide repeats in the gene coding for the N-terminal region of the huntingtin (Htt) protein, which leads to the formation of a polyglutamine stretch. The greater the CAG repeats, the earlier the onset of the disease. The polyglutamine stretch destabilizes the Htt protein leading to misfolding, abnormal processing, aggregation, and inclusion formation. Mutant Htt protein is believed to damage and kill neurons in the striatum by a mechanism involving increased oxidative and metabolic stress, and impaired adaptive cellular stress responses. A large number of abnormalities have been reported in HD, including transcription deficits, energy impairment, excitotoxicity, and lack of trophic support. Reduced trophic support contributes importantly to striatal degeneration in human HD. Specifically, brain-derived neurotrophic factor (BDNF) expression is reduced in patients with HD. BDNF is also decreased in brain tissue from mice transgenic for mutant Htt. BDNF levels influences the onset and the severity of motor dysfunction in HD mice. In addition to BDNF, levels of the molecular chaperones heat shock proteins (Hsp40 and 70) decrease progressively in HD brain. Hsp70 is a highly stress-inducible member of a chaperone family of proteins that functions to prevent misfolding and aggregation of newly synthesized mutant proteins and stress-denatured proteins. Hsps appear to play a critical role in HD since expression of active heat shock factor HSF1, a transcription factor responsible for the induction of Hsps, markedly reduces polyglutamine aggregate formation in both cell and mouse models. Many efforts have been made to develop preventive treatments for HD because of the strong genetic link and a freely available genetic test to identify individuals at risk. At present, only symptomatic therapy is available and effective therapeutic approaches to slow the disease process have yet to be developed. Previous studies have shown that electroconvulsive shock (ECS) induces the production of growth factors including BDNF and the molecular chaperones HSP40 and HSP70. Because ECS can stimulate the production of neuroprotective proteins, we determined whether ECS treatment could slow the progressive nature of the disease process and provide a therapeutic benefit in a mouse model of HD. ECS or sham treatment was administered to male N171-82Q Htt mutant mice. End points measured included motor function, striatal and cortical pathology, and levels of neurotrophic factors, protein chaperones, and proteins involved in synaptic plasticity. ECS treatment delayed the onset of motor symptoms, reduced body weight loss and extended the survival of HD mice. Striatal neurodegeneration was attenuated and levels of neurotrophic factors, protein chaperones and mitochondria-stabilizing protein were elevated in striatal cells of ECS-treated compared to sham-treated HD mice. Our findings suggest that ECS can increase the resistance of neurons to mutant huntingtin resulting in improved functional outcome and extended survival. The potential of ECS as a treatment for HD patients merits further consideration.
Show less - Date Issued
- 2010
- Identifier
- CFE0003486, ucf:48981
- Format
- Document (PDF)
- PURL
- http://purl.flvc.org/ucf/fd/CFE0003486
- Title
- Role of brain derived neurotrophic factor (BDNF) in stimulating strength improvements induced by short-term resistance training.
- Creator
-
Church, David, Hoffman, Jay, Stout, Jeffrey, Fukuda, David, Stock, Matt, University of Central Florida
- Abstract / Description
-
Strength adaptations from short-term resistance training are thought to be related primarily to neurological adaptations. Considering brain-derived neurotrophic factor (BDNF) role in the nervous system, it is possible that BDNF has a role in these adaptations. Fourteen untrained males were randomized into either a resistance training (RT; n =8) or control (CON; n=6) group. Motor unit (MU) recruitment at 50% and 80% of each participant's maximal voluntary isometric contraction (MVIC), muscle...
Show moreStrength adaptations from short-term resistance training are thought to be related primarily to neurological adaptations. Considering brain-derived neurotrophic factor (BDNF) role in the nervous system, it is possible that BDNF has a role in these adaptations. Fourteen untrained males were randomized into either a resistance training (RT; n =8) or control (CON; n=6) group. Motor unit (MU) recruitment at 50% and 80% of each participant's maximal voluntary isometric contraction (MVIC), muscle cross sectional area (CSA) and thickness (MT), as well as one-repetition maximum (1RM) of the squat (SQT), leg press (LP), and leg extension (LE) were performed before (PRE) and after (POST) the training period. Following the MU assessment, the recruitment threshold (RT; % MVIC) and mean firing rate (MFR; pulse per second [pps]) of each MU were determined. Linear regression was used to quantify the slope (pps/% MVIC) and y-intercept (pps) of the MFR versus RT relationship for each participant and time point. Participants completed an acute resistance exercise bout at PRE and POST consisting of 3 sets of 8 (-) 10 repetitions with 90 seconds of rest between each set of SQT, LP, and LE. Blood samples were obtained following a 4-hour fast before (BL), immediately-(IP), and one-(1H) hour post resistance exercise. RT subjects performed the same resistance exercise protocol at PRE twice a week for 3-weeks. CON subjects were instructed to not perform any resistance exercise. Area under the curve (AUC) analysis was determined by the trapezoidal method. Pearson product-moment correlations were used to examine selected bivariate relationships. The ?BDNF AUC was significantly correlated to the relative 80% ?y-intercept (r=-0.626, p=0.030), and trended to be correlated to the relative 80% ?slope (r=0.551, p=0.063). Our results indicate that ? in plasma BDNF concentrations appear to be related to ?'s MU recruitment at high intensities (80% of MVIC) of exercise.
Show less - Date Issued
- 2018
- Identifier
- CFE0006988, ucf:51665
- Format
- Document (PDF)
- PURL
- http://purl.flvc.org/ucf/fd/CFE0006988
