No description available.

No description available.

Alzheimer’s disease (AD), an age-related neurodegenerative disorder, progresses across a continuum of severity that leads to serious neurological dysfunction and eventually death. Initially manifesting as mild impairment in cognition and executive function, AD eventually leads to serious disturbances in memory, decision-making, language, mobility and sensing the environment. AD affects approximately 27 million people worldwide, over 5 million in the United States alone, and is one of the most debilitating diseases that costs society billions of dollars annually and is a primary cause of death in the elderly. Pharmacological treatments produce only moderate symptomatic benefits and do not attenuate or prevent the progression of AD with some medications associated with increased symptomatic behavior such as decreased motor function and increased likelihood of falls. Conversely, research utilizing animal models indicates exercise may play an important role to attenuate AD symptoms and delaying AD onset as regular aerobic activity increases the expression of brain-derived neurotrophic factor, a peptide that plays a major role in neural function, neural plasticity, and attenuation of neuritic plaque; a ß-amyloid derived plaque that is recognized as the primary cause of neural degradation associated with AD. To examine this exercise hypothesis, participants (N = 19; mean age 85.5 ±5.2 years) completed a single treatment, regular walking activity over time (30-min per day, 3 days per week for 12 weeks), with pre-test post-test evaluations undertaken utilizing valid research instruments designed to measure cognition, executive function, and motor capabilities in persons with AD. T-test with repeated measures ANOVA with various categorical variables as between-group factors were used to test the hypothesis. Analysis of change indicated significant change occurred in Cognitive function [t(18) = 5.74, p < .001], Balance [t(18) = 7.43, p < .001], and Mobility [t(18) = 3.82, p < .001], with no significant change in Activities of Daily Living (t[18] = 1.48, p < .156). A significant decrease in the number of falls was also found (z = 2.392, p < .017). No main effect was associated with AD stage, gender, or education level. The results of this study indicate regular aerobic activity enhances neural function in persons with AD, thus supporting the exercise hypothesis which posits regular aerobic exercise attenuates AD symptoms and delays AD onset. While the results provide important evidence regarding the impact of aerobic exercise on neural function in the AD populations, further research is necessary to identify the mechanisms by which brain-derived neurotrophic factor is induced with exercise and to examine the effectiveness of different exercise modalities (e.g., specificity, duration, and intensity) on neural function in the AD population. / Kinesiology

Schizophrenia is a debilitating neuropsychiatric disorder that affects approximately one percent of the global population. Aberrant N-methyl-D-aspartate receptors and endoplasmic reticulum stress have been implicated in the pathogenesis of schizophrenia. Despite a century of extensive research, outcomes from best-practice treatments remain dismal. Lurasidone hydrochloride is a novel atypical antipsychotic drug with a unique receptor binding profile that can potentially treat the heterogeneous symptomology of schizophrenia. However, discrepancies in experimental design (i.e. animal models used, symptoms assessed etc.) have yielded conflicting results surrounding the procognitive and antidepressant properties of lurasidone. Furthermore, the limited aqueous solubility of lurasidone poses a considerable challenge for improving antipsychotic drug delivery to the brain and limiting the prevalence of adverse side effects. These obstacles coupled with the elusive pathophysiology of schizophrenia and its incurable nature, highlight the importance of investigating novel therapeutic targets and their underlying mechanisms to improve treatment and enhance the quality of life of patients with schizophrenia. This thesis sought to accomplish three primary objectives: (1) validate the behavioural efficacy of lurasidone hydrochloride; (2) investigate the role of mesencephalic astrocyte-derived neurotrophic factor as a potential therapeutic target of lurasidone; and (3) evaluate the therapeutic potential of intranasal lurasidone administration as a novel method for antipsychotic drug delivery. The data presented within this thesis suggest that repeated lurasidone treatment may be effective at treating the positive, negative, and cognitive symptoms of schizophrenia, but not sensorimotor gating deficits. Furthermore, sub-chronic lurasidone treatment in rats significantly increased the relative expression of mesencephalic astrocyte-derived neurotrophic factor in the rat prefrontal cortex, a primary site of impairment observed in schizophrenia. Lastly, we conclude that lurasidone administered via the nasal route using a novel poly(oligo ethylene glycol methacrylate)-based nanogel formulation required four times less drug to achieve a therapeutic response comparable to traditional intraperitoneal routes. The findings presented within this thesis suggest that lurasidone might be a favourable atypical antipsychotic drug that exerts its therapeutic effects through the modulation of neurotrophic factor expression in the brain regions affected by schizophrenia. This thesis offers new insight that can help guide future studies toward improving the prognosis of patients suffering from schizophrenia. / Thesis / Master of Science (MSc)

Syfte Syftet med denna litteraturstudie var att redovisa vilken typ av träning (träningsform, intensitet, frekvens, träningspassduration och interventionsduration) som påverkar vilonivåer av BDNF hos friska vuxna. Metod För att besvara syftet gjordes en litteraturstudie. Litteratursökningar utfördes i databaserna PubMed, Web of Science och SPORTDisucs vilka gav 18 inkluderade artiklar. Träningsinterventionerna redovisades utifrån träningsform, intensitet, duration och frekvens. Resultatet redovisade de ingående gruppernas procentuella förändring gällande vilonivåer av BDNF samt tillhörande signifikansnivå. Resultat Av 18 inkluderade artiklar påvisade fem en signifikant skillnad i vilonivåer av BDNF, medan 13 artiklar inte visade någon signifikant skillnad. Slutsatser Utifrån resultatet kan inga generella slutsatser dras om träningsupplägg som påverkar vilonivåer av BDNF hos friska vuxna. Troligtvis skiljer sig den träningsinducerade responsen på vilonivåer av BDNF i olika kombinationer av träningsform, intensitet, frekvens, interventionsduration och träningspassduration. Responsen är således en komplex funktion beroende på ett flertal faktorer som såväl träningsupplägg och individuella faktorer. Regelbunden träning ger förmodligen en förändrad respons på BDNF-genuttryck, oavsett om vilonivåerna påverkas eller inte, vilket på sikt gynnar hjärnhälsan.

Yes / Evidence suggests that flavonoid-rich foods are capable of inducing improvements in memory and cognition in animals and humans. However, there is a lack of clarity concerning whether flavonoids are the causal agents in inducing such behavioral responses. Here we show that supplementation with pure anthocyanins or pure flavanols for 6 weeks, at levels similar to that found in blueberry (2% w/w), results in an enhancement of spatial memory in 18 month old rats. Pure flavanols and pure anthocyanins were observed to induce significant improvements in spatial working memory (p = 0.002 and p = 0.006 respectively), to a similar extent to that following blueberry supplementation (p = 0.002). These behavioral changes were paralleled by increases in hippocampal brain-derived neurotrophic factor (R = 0.46, p<0.01), suggesting a common mechanism for the enhancement of memory. However, unlike protein levels of BDNF, the regional enhancement of BDNF mRNA expression in the hippocampus appeared to be predominantly enhanced by anthocyanins. Our data support the claim that flavonoids are likely causal agents in mediating the cognitive effects of flavonoid-rich foods.

Yes / Background: Platelet rich plasma (PRP), processed from autologous peripheral blood, is used to treat androgenetic alopecia (AGA). Objective: To determine the efficacy of PRP for hair growth promotion in AGA patients in a randomized, blinded, placebo controlled, pilot clinical trial (NCT02074943). Methods: The efficacy of an 8 week, 5 session, PRP treatment course was determined by measuring hair density and hair caliber changes in 10 AGA affected patients. For each PRP sample, the concentrations of selected growth factors were determined using a multiplex assay system. The clinical results were then correlated to the growth factor concentrations in PRP. Results: At 16 weeks, 8 weeks after the last PRP injection, treated areas exhibited increased mean hair density (+12.76%) over baseline compared to placebo (+0.99%). Mean hair caliber decreased in both treated and placebo regions (-16.22% and -19.46% respectively). Serial analysis of PRP significant variability in concentrations between patients. Overall, there was a positive correlation between GDNF concentration and hair density (p= 0.004). Trends, though not statistically significant, were also observed for FGF2 and VEGF. Limitations: Small sample size and lack of comparative cohorts receiving protocol variations limit confidence in the study data. Conclusions: This small pilot clinical trial suggests PRP treatment may be beneficial for AGA. However, the variable hair growth responses between patients indicate there is a significant opportunity to improve PRP therapy protocols for hair growth promotion. The variability in growth factor concentration in PRP suggests standardization of growth factors post-processing might improve hair growth responses. / RepliCel Life Sciences Inc. (Canada)

<p>Amyotrophic lateral sclerosis is a fatal, progressive neurodegenerative disease with unknown ethiology. The aim of this study was to increase understanding of the pathophysiological mechanisms of dying motor neurons and wasting muscle tissue in this particular disorder.</p><p>Quantitative receptor autoradiographic methodology was applied on cervical spinal cord sections from patients with ALS to evaluate the specific binding of the acetylcholine transporter ³H-vesamicol in motor neurons. Despite a significant reduction of the number of ventral motor neurons in ALS, the ³H-vesamicol binding was not reduced in ALS compared to control cases, which suggests an increased metabolic activity in remaining motor neurons.</p><p>Motor neurons dying in ALS might go through apoptosis (programmed cell death), so immunohistochemical and TUNEL techniques were applied on thoracic spinal cord from ALS patients to evaluate the possibility of an apoptotic process. The increased Bax expression indicates an apoptotic process and further, motor neurons were TUNEL-positive, indicating DNA degradation caused by programmed cell death.</p><p>Muscle biopsies were obtained from ALS patients, and mRNA levels for the neurotrophic factors GDNF and BDNF were measured and compared to control subjects. GDNF levels were increased in muscle tissue in ALS whereas BDNF levels were unaltered.</p><p>Levels of GDNF and BDNF were also measured in cerebrospinal fluid from ALS patients and controls using ELISA methodology. Levels of BDNF were unaltered in ALS cornpared to controls. GDNF however was not detectable in controls whereas 12 out of 15 ALS patients had measurab1e levels of GDNW. A marked upregulation of endogenous GDNF and GDNF mRNA in ALS CSF and muscle respectively is of special interest in relation to clinical trials where GDNF is administered to this group of patients.</p>

Amyotrophic lateral sclerosis is a fatal, progressive neurodegenerative disease with unknown ethiology. The aim of this study was to increase understanding of the pathophysiological mechanisms of dying motor neurons and wasting muscle tissue in this particular disorder. Quantitative receptor autoradiographic methodology was applied on cervical spinal cord sections from patients with ALS to evaluate the specific binding of the acetylcholine transporter 3H-vesamicol in motor neurons. Despite a significant reduction of the number of ventral motor neurons in ALS, the 3H-vesamicol binding was not reduced in ALS compared to control cases, which suggests an increased metabolic activity in remaining motor neurons. Motor neurons dying in ALS might go through apoptosis (programmed cell death), so immunohistochemical and TUNEL techniques were applied on thoracic spinal cord from ALS patients to evaluate the possibility of an apoptotic process. The increased Bax expression indicates an apoptotic process and further, motor neurons were TUNEL-positive, indicating DNA degradation caused by programmed cell death. Muscle biopsies were obtained from ALS patients, and mRNA levels for the neurotrophic factors GDNF and BDNF were measured and compared to control subjects. GDNF levels were increased in muscle tissue in ALS whereas BDNF levels were unaltered. Levels of GDNF and BDNF were also measured in cerebrospinal fluid from ALS patients and controls using ELISA methodology. Levels of BDNF were unaltered in ALS cornpared to controls. GDNF however was not detectable in controls whereas 12 out of 15 ALS patients had measurab1e levels of GDNW. A marked upregulation of endogenous GDNF and GDNF mRNA in ALS CSF and muscle respectively is of special interest in relation to clinical trials where GDNF is administered to this group of patients.

Recent research, that has been focused on recognition memory, has revealed that two processes contribute to recognition of previously encountered items: recollection and familiarity (Aggleton & Brown, 1999; Eichenbaum, 2006; Eichenbaum, Yonelinas, & Ranganath, 2007; Rugg & Yonelinas, 2003; Skinner & Fernandes, 2007; Squire, Stark, & Clark, 2004; Wixted, 2007a; Yonelinas, 2001a; Yonelinas, 2002). The findings of neural correlates of recollection and familiarity lead to the assumption that there are different brain regions activated in either process, but there are, to the best of my knowledge, no studies assessing how these brain regions are working together in a recollection or a familiarity network, respectively. Additionally, there are almost no studies to date, which directly searched for overlapping regions. Therefore, in study I of the current thesis, brain regions associated to both recognition processes are searched investigated. Additionally, a connectivity analysis will search for functional correlated brain activations that either build a recollection or a familiarity network. It is undoubtable that the Brain Derived Neurotrophic Factor (BDNF) is strongly involved in synaptic plasticity in the hippocampus (Bramham & Messaoudi, 2005) and there is evidence that a genetic variant of this neurotrophin (BDNF 66Met) is related to poorer memory performance (Egan, et al., 2003). Therefore, in study II of the current thesis, the effect of BDNF Val66Met on recollection and familiarity performance and related brain activations is investigated. Finally, one could summarize, that serotonin, like BDNF, is strongly involved in brain development and plasticity as well as in learning and memory processes (Vizi, 2008). More precisely, there is evidence for alterations in the structure of brain regions, which are known to be involved in emotional memory formation and retrieval, like amygdala and hippocampus (Frodl, et al., 2008; Munafo, Brown, & Hariri, 2008; Pezawas, et al., 2005). One study found an slight epistatic effect of BDNF and 5-HTTLPR on the grey matter volume of the amygdala (Pezawas, et al., 2008). Therefore, in study III, it is investigated if such an interaction effect could be substantiated for the amygdala and additionally revealed for the hippocampus. The results of the current thesis allow further comprehension of recollection, hence episodic memory, and point to a special role of the BDNF in temporal and prefrontal brain regions. Additionally, the finding of an epistatic effect between BDNF and serotonin transporter function point to the need of analyzing interactions between genes and also between genes and environmental factors which reveals more information than the study of main effects alone. In conclusion, analyzing behavioral and neural correlates of episodic memory reveal allowed insights in brain functions that may serve as guideline for future studies in clinical populations with memory deficits, including susceptibility factors such as good or bad environment, as well as promising gene variants that influence episodic memory.