The current study analyzed the effects of environmental enrichment versus isolation housing on the behavioral sensitization to nicotine in the neonatal quinpirole (NQ; dopamine D2-like agonist) model of dopamine D2 receptor supersensitivity, a rodent model of schizophrenia. NQ treatment in rats increases dopamine D2 receptor sensitivity throughout the animal's lifetime, consistent with schizophrenia. Animals were administered NQ (1 mg/kg) or saline (NS) from postnatal day (P)1 to P21, weaned, and immediately placed into enriched housing or isolated in wire cages throughout the experiment. Rats were behaviorally sensitized to nicotine (0.5 mg/kg base) or saline every consecutive day from P38 to P45, and brain tissue was harvested at P46. Results revealed that neither housing condition reduced nicotine sensitization in NQ rats, whereas enrichment reduced sensitization to nicotine in NS-treated animals. The nucleus accumbens (NAcc) was analyzed for glial cell line-derived neurotrophic factor (GDNF), a neurotrophin important in dopamine plasticity. Results were complex, and revealed that NAcc GDNF was increased in animals given nicotine, regardless of housing condition. Further, enrichment increased GDNF in NQ rats regardless of adolescent drug treatment and in NS-treated rats given nicotine, but did not increase GDNF in NS-treated controls compared to the isolated housing condition. This study demonstrates that environmental experience has a prominent impact on the behavioral and the neural plasticity NAcc response to nicotine in adolescence.

This study examined if multi-joint resistance exercises could elicit expression of biomarkers associated with neuroprotection. Thirteen well-trained males performed 4 sets to failure at 80% of a one-repetition maximum (1RM) on the back squat, bench press, and deadlift. The biomarkers measured immediately pre- and post-exercise were brain derived neurotrophic factor (BDNF), insulin-like growth factor 1 (IGF-1), cathepsin B (CatB), and interleukin 6 (IL-6). There was a main time effect (p<0.01) for BDNF with significant increases in the deadlift (p=0.01) and bench press (p=0.01) conditions, but not the squat (p=0.21). There was a main time effect (p<0.01) for IL-6 with a significant increase in the squat (p<0.01). There was no significant increase in CatB or IGF-1 (p>0.05). Additionally, there was no significant relationship between BDNF and IL-6 response. / Includes bibliography. / Thesis (M.S.)--Florida Atlantic University, 2019. / FAU Electronic Theses and Dissertations Collection

Neuropeptides, such as substance P (SP) and bombesin/gastrin-releasing peptide (BN/GRP), and neurotrophins are involved in neuro-immunomodulatory processes and have marked trophic, growth-promoting and inflammation-modulating properties. The impact of these modulators in rheumatoid arthritis (RA) is, however, unclear. An involvement of the innervation, including the peptidergic innervation, is frequently proposed as an important factor for arthritic disease. Many patients with RA, but not all, benefit from treatment with anti-TNF medications. The studies presented here aimed to investigate the roles of neuropeptides, with an emphasis on BN/GRP and SP, and neurotrophins, especially with attention to brain-derived neurotrophic factor (BDNF), in human and murine knee joint tissue. The expression patterns of these substances and their receptors in synovial tissue from patients with either RA or osteoarthritis (OA) were studied in parallel with the levels of these factors in blood and synovial fluid from patients with RA and from healthy controls. Correlation studies were also performed comparing the levels of neuropeptides with those of pro-inflammatory cytokines [tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6)]. Furthermore, the impact of anti-TNF treatment on the levels of BDNF in blood was investigated. In a murine model of RA, the expression of these substances on articular chondrocytes along with their expression in synovial tissue was investigated. The expression of BN/GRP in human synovial tissue was confined to fibroblast-like and mononuclear-like cells whereas SP was detected in nerve-related structures. Receptors for these neuropeptides (GRP-R and NK-1R) were frequently present in blood vessel walls, and on fibroblast-like and mononuclear-like cells. The expression of BDNF and its receptors, p75 neurotrophin receptor and TrkB, was mainly confined to nerve structures. The levels of SP, and particularly those of BN/GRP, in synovial fluid and peripheral blood correlated with the levels of pro-inflammatory cytokines. There were clearly more correlations between SP-BN/GRP and inflammatory parameters than between BDNF and these factors. Plasma levels of BDNF were decreased following anti-TNF-treatment. In the joints of the murine model, there was a marked expression of neurotrophins, neurotrophin receptors and NK-1R/GRP-R in the articular chondrocytes. The expression was down-regulated in the arthritic animals. A neurotrophin system was found to develop in the inflammatory infiltrates of the synovium in the arthritic mice. The results presented suggest that there is a local, and not nerve-related, supply of BN/GRP in the human synovial tissue. Furthermore, BN/GRP and SP have marked effects in the synovial tissue of patients with RA, i.e., there were abundant receptor expressions, and these neuropeptides are, together with cytokines, likely to be involved in the neuro-immunomodulation that occurs in arthritis. The observations do on the whole suggest that the neuropeptides, rather than BDNF, are related to inflammatory processes in the human knee joint. A new effect of anti-TNF treatment; i.e., lowering plasma levels of BDNF, was observed. Severe arthritis, as in the murine model, lead to a decrease in the levels of neurotrophin, and neurotrophin and neuropeptide receptor expressions in the articular cartilage. This fact might be a drawback for the function of the chondrocytes. Certain differences between the expression patterns in the synovial tissue of the murine model and those of human arthritic synovial tissue were noted. It is obvious that local productions in the synovial tissue, nerve-related supply in this tissue and productions in chondrocytes to different extents occur for the investigated substances.

Electroconvulsive therapy (ECT) is one of the oldest and most effective treatments for depression; however, its biological underpinnings are poorly understood. Brain-derived neurotrophic factor (BDNF) and the hypothalamic-pituitary-adrenal (HPA) axis are two chemical messenger systems implicated in the antidepressant action and cognitive side effects of ECT. The Wistar-Kyoto (WKY) strain is a genetic model of depression that shows biological, cognitive, behavioural, and treatment-response abnormalities, making it potentially a useful model in which to investigate the underpinnings of the action of electroconvulsive stimulus (ECS: the amimal model of ECT). In addition, the WKY presents a potentially useful model for translational research on depression. The WKY strain is particularly valuable for the measurement of serum BDNF protein, for which the association with antidepressant treatments is much less clear (mostly stemming from investigations in humans) than that between brain BDNF and antidepressant treatments in rodent studies. The three studies presented add insight into the biological and behavioural effects of ECS. The first study (chapter 2) found no evidence of increased (R)-[11C]rolipram binding (an indirect marker of cyclic-adenosine monophosphate, cAMP) in the brain, despite significant increases of brain BDNF protein expression after repeated ECS. The second study (chapter 3) demonstrated the validity of the WKY strain in the investigation of ECS. Relative to Wistar controls, WKY showed similar antidepressant and cognitive effects (despite some abnormal behavioural responses), immediate but not sustained increases in brain BDNF protein, and a novel finding of increased extra-hypothalamic CRF after 5 daily ECS. The final study (chapter 4) demonstrated baseline strain differences in serum (WKY < Wistar) but not brain BDNF and, in both strains, no change in serum BDNF despite significant changes in brain BDNF after repeated ECS treatment. Preliminary results from a human pilot study investigating similar measures in a small group of people receiving ECT for depression are also presented. The results of this body of work advance our understanding of the activation and role of brain and serum measures of BDNF and the HPA axis in ECS/ECT, and raise important issues in the translation of research from basic science to the human condition of depression.

Electroconvulsive therapy (ECT) is one of the oldest and most effective treatments for depression; however, its biological underpinnings are poorly understood. Brain-derived neurotrophic factor (BDNF) and the hypothalamic-pituitary-adrenal (HPA) axis are two chemical messenger systems implicated in the antidepressant action and cognitive side effects of ECT. The Wistar-Kyoto (WKY) strain is a genetic model of depression that shows biological, cognitive, behavioural, and treatment-response abnormalities, making it potentially a useful model in which to investigate the underpinnings of the action of electroconvulsive stimulus (ECS: the amimal model of ECT). In addition, the WKY presents a potentially useful model for translational research on depression. The WKY strain is particularly valuable for the measurement of serum BDNF protein, for which the association with antidepressant treatments is much less clear (mostly stemming from investigations in humans) than that between brain BDNF and antidepressant treatments in rodent studies. The three studies presented add insight into the biological and behavioural effects of ECS. The first study (chapter 2) found no evidence of increased (R)-[11C]rolipram binding (an indirect marker of cyclic-adenosine monophosphate, cAMP) in the brain, despite significant increases of brain BDNF protein expression after repeated ECS. The second study (chapter 3) demonstrated the validity of the WKY strain in the investigation of ECS. Relative to Wistar controls, WKY showed similar antidepressant and cognitive effects (despite some abnormal behavioural responses), immediate but not sustained increases in brain BDNF protein, and a novel finding of increased extra-hypothalamic CRF after 5 daily ECS. The final study (chapter 4) demonstrated baseline strain differences in serum (WKY < Wistar) but not brain BDNF and, in both strains, no change in serum BDNF despite significant changes in brain BDNF after repeated ECS treatment. Preliminary results from a human pilot study investigating similar measures in a small group of people receiving ECT for depression are also presented. The results of this body of work advance our understanding of the activation and role of brain and serum measures of BDNF and the HPA axis in ECS/ECT, and raise important issues in the translation of research from basic science to the human condition of depression.

This thesis presents the first randomised controlled trial (RCT) to investigate whether supplemented probiotic bacteria-"live microorganisms that, when administered in adequate amounts, confer a health benefit on the host" (Sanders, 2008)-affect mood and other psychological outcomes in people presenting with low mood. Seventy-nine participants with at least moderate symptoms of depression were randomised in a double-blind manner to receive either a probiotic preparation containing Lactobacillus helveticus and Bifidobacterium longum or a matched placebo for eight weeks. The RCT phase was followed by an open label extension in which all participants were offered the active study product for a further 8 weeks. Participants were followed up at 6 months post-study. Based on the existing evidence from gut-brain axis research, and on models linking depression with inflammation, immune activation, low vitamin D levels, and the gut microbiota (outlined in Chapters 1 and 2), it was hypothesised that: the overall sample would have elevated levels of inflammatory biomarkers and low levels of vitamin D at baseline, and that this would be associated with scores on psychological and irritable bowel syndrome (IBS) outcome measures; that group differences (active treatment versus placebo) would be observed in scores on psychological outcome measures after eight weeks of probiotic intervention; that group differences would also be observed in blood levels of proinflammatory cytokines, hsCRP, vitamin D and BDNF, and scores on a measure of gut function/IBS, and that levels of these variables may predict or impact on treatment response; and that group differences would be observed on outcome measures at the point of the 6-month follow-up between those who continued to take the probiotic and those who discontinued probiotic use. In total, 58 of the 77 participants who provided baseline blood samples (75%) had at least one marker of inflammation elevated outside the normal reference range at baseline. Baseline vitamin D was approaching the deficient level, displayed a seasonal pattern, and was associated with severity on one measure of cognition. No significant differences were found between the active treatment and placebo groups on any psychological outcome measure, the measure of gut function or in the level of any blood-based biomarker in the randomised phase. Baseline vitamin D level was found to moderate treatment effect on several outcome measures. The results of the open label extension supported the lack of efficacy observed in the randomised phase, and also allowed for the comparison of efficacy over intervention periods of varying durations. The results of the follow-up at 6 months post-trial indicated that, while mean scores on psychological outcome measures remained lower than baseline, there was regression on some outcome measures after the study. When the participants who replied to the 6 month follow-up questionnaire were divided into groups based on their self-reported dominant treatment since the trial (probiotics/nutrition, standard treatment or no treatment) there was no difference in mood or other psychological outcomes among the groups at 6 months. The current trial found no evidence that this probiotic formulation is effective in treating the symptoms of depression or IBS, or in moderating the levels of inflammatory and other biomarkers in a sample recruited with moderate depression. This finding does not support the theory proposed in several narrative reviews which suggests probiotics as a possible intervention for depression and other mental health outcomes, but is supported by the systematic review of human probiotics studies presented in Chapter 3 which found overall limited evidence of probiotic efficacy for psychological outcomes. Future studies in the area should attempt to further broaden this field, in particular by recruiting samples with mild and/or non-chronic depression for interventional studies, or by approaching probiotics as a preventative or adjuvant treatment strategy for depression.

Older adults who stay physically and mentally active appear to have better cognitive function compared to their less active counterparts. In fact, those who perform either regular exercise or cognitive training (CT) can maintain and improve their cognitive functioning, even in their later years. Resistance training (RT) causes an increase in specific hormones that are responsible for improved brain functioning; however, many questions about how these hormones respond to RT are unanswered. Understanding how these hormones respond to RT can help researchers and clinicians create optimal training programs for older adults. Research shows that combining exercise and CT may be better for the brain compared to either activity performed alone; however, nobody has looked at RT combined with CT. We believe that combining RT and CT where CT is performed when an individual’s hormones are highest (right after RT) could have a big effect on brain function in a short period of time. This work represents a two-part study looked at: 1) how these hormones respond to a session of RT, and 2) the effect of combined RT and CT on cognitive function in older adults. Our participants performed CT immediately after RT, 3 times per week for 8 weeks. Specific hormones which are important for brain function were measured immediately before and for 2 hours after an acute bout of RT before and after 8-weeks of RT. Cognitive function was measured before and after the RT training period. Our primary findings were: 1) significant increases in brain derived neurotrophic factor immediately after RT and 2) participants cognitive function improved after 8 weeks of training. This is important because short-term combined RT and CT can lead to significant improvements in cognitive functioning. Also, this work will allow researchers to begin designing exercise programs that can maximize the brain’s ability to change, even at an old age. / Thesis (Master, Kinesiology & Health Studies) -- Queen's University, 2012-09-21 15:29:35.509

Electroconvulsive therapy (ECT) is one of the oldest and most effective treatments for depression; however, its biological underpinnings are poorly understood. Brain-derived neurotrophic factor (BDNF) and the hypothalamic-pituitary-adrenal (HPA) axis are two chemical messenger systems implicated in the antidepressant action and cognitive side effects of ECT. The Wistar-Kyoto (WKY) strain is a genetic model of depression that shows biological, cognitive, behavioural, and treatment-response abnormalities, making it potentially a useful model in which to investigate the underpinnings of the action of electroconvulsive stimulus (ECS: the amimal model of ECT). In addition, the WKY presents a potentially useful model for translational research on depression. The WKY strain is particularly valuable for the measurement of serum BDNF protein, for which the association with antidepressant treatments is much less clear (mostly stemming from investigations in humans) than that between brain BDNF and antidepressant treatments in rodent studies. The three studies presented add insight into the biological and behavioural effects of ECS. The first study (chapter 2) found no evidence of increased (R)-[11C]rolipram binding (an indirect marker of cyclic-adenosine monophosphate, cAMP) in the brain, despite significant increases of brain BDNF protein expression after repeated ECS. The second study (chapter 3) demonstrated the validity of the WKY strain in the investigation of ECS. Relative to Wistar controls, WKY showed similar antidepressant and cognitive effects (despite some abnormal behavioural responses), immediate but not sustained increases in brain BDNF protein, and a novel finding of increased extra-hypothalamic CRF after 5 daily ECS. The final study (chapter 4) demonstrated baseline strain differences in serum (WKY < Wistar) but not brain BDNF and, in both strains, no change in serum BDNF despite significant changes in brain BDNF after repeated ECS treatment. Preliminary results from a human pilot study investigating similar measures in a small group of people receiving ECT for depression are also presented. The results of this body of work advance our understanding of the activation and role of brain and serum measures of BDNF and the HPA axis in ECS/ECT, and raise important issues in the translation of research from basic science to the human condition of depression.

Thesis (Ph. D.)--University of Washington, 2007. / Vita. Includes bibliographical references (leaves 95-113).

Thesis (Ph. D.)--University of Alabama at Birmingham, 2008. / Title from first page of PDF file (viewed Sept. 16, 2008). Includes bibliographical references.