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1.
Methods ; 226: 28-34, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38608850

ABSTRACT

It is generally accepted that mineral deficiencies, including magnesium and calcium, are widespread globally. Dietary supplementation may be an effective approach to combat such deficiencies. However, challenges associated with limited mineral solubility in the digestive system can impede effective dissolution and hinder absorption, leading to deficiency, and undesirable gastrointestinal disturbances including diarrhoea. Seawater is considered to be a rich source of bioactive magnesium, calcium, and 72 other trace minerals. In this study, we examine two different marine-derived multimineral products as potential dietary supplements. Aquamin-Mg, sourced from seawater is rich in magnesium (12%), and Aquamin F, a seaweed-derived multimineral is rich in calcium (32%). Both products also contain a diverse array of over 72 minerals, characteristic of their oceanic origin. Our study comprises two experiments. The first experiment evaluates and compares the solubility of Aquamin-Mg, commercially available magnesium bisglycinate, and Pure Magnesium Bisglycinate (PrizMAG) during in vitro digestion using the INFOGEST method. Results demonstrate that Aquamin-Mg exhibits superior solubility than the other magnesium sources during the gastric and intestinal phases, particularly when administered alongside food materials. The second experiment is a randomized, double-blind, placebo-controlled study in a small cohort of healthy older aged adults to assess the tolerability of a combined Aquamin-Mg/Aquamin-F supplement over a 12-week period. The findings indicate that this combination supplement is well-tolerated, with no significant adverse events reported, emphasizing its potential as a means of addressing mineral deficiencies.


Subject(s)
Calcium , Dietary Supplements , Magnesium , Humans , Magnesium/chemistry , Dietary Supplements/analysis , Calcium/chemistry , Calcium/metabolism , Female , Male , Aged , Double-Blind Method , Solubility , Seawater/chemistry , Digestion , Middle Aged , Biological Availability , Seaweed/chemistry , Adult , Minerals
2.
Transl Psychiatry ; 14(1): 195, 2024 Apr 24.
Article in English | MEDLINE | ID: mdl-38658547

ABSTRACT

Lifestyle factors, especially exercise, impact the manifestation and progression of psychiatric and neurodegenerative disorders such as depression and Alzheimer's disease, mediated by changes in hippocampal neuroplasticity. The beneficial effects of exercise may be due to its promotion of adult hippocampal neurogenesis (AHN). Gut microbiota has also been showed to be altered in a variety of brain disorders, and disturbances of the microbiota have resulted in alterations in brain and behaviour. However, whether exercise can counteract the negative effects of altered gut microbiota on brain function remains under explored. To this end, chronic disruption of the gut microbiota was achieved using an antibiotic cocktail in rats that were sedentary or allowed voluntary access to running wheels. Sedentary rats with disrupted microbiota displayed impaired performance in hippocampal neurogenesis-dependent tasks: the modified spontaneous location recognition task and the novelty suppressed feeding test. Performance in the elevated plus maze was also impaired due to antibiotics treatment. These behaviours, and an antibiotics-induced reduction in AHN were attenuated by voluntary exercise. The effects were independent of changes in the hippocampal metabolome but were paralleled by caecal metabolomic changes. Taken together these data highlight the importance of the gut microbiota in AHN-dependent behaviours and demonstrate the power of lifestyle factors such as voluntary exercise to attenuate these changes.


Subject(s)
Behavior, Animal , Gastrointestinal Microbiome , Hippocampus , Neurogenesis , Physical Conditioning, Animal , Animals , Gastrointestinal Microbiome/physiology , Neurogenesis/physiology , Physical Conditioning, Animal/physiology , Rats , Male , Behavior, Animal/physiology , Anti-Bacterial Agents/pharmacology , Rats, Sprague-Dawley , Sedentary Behavior
3.
Microb Biotechnol ; 17(4): e14462, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38593310

ABSTRACT

Alzheimer's disease is a complex and progressive condition that affects essential neurological functions such as memory and reasoning. In the brain, neuronal loss, synaptic dysfunction, proteinopathy, neurofibrillary tangles, and neuroinflammation are the hallmarks of Alzheimer's disease pathophysiology. In addition, recent evidence has highlighted that microbes, whether commensal or pathogenic, also have the ability to interact with their host and to regulate its immune system, therefore participating in the exchanges that lead to peripheral inflammation and neuropathology. Because of this intimate relationship, bacteria, viruses, fungi, and protozoa have been implicated in the development of Alzheimer's disease. Here, we bring together current and most recent evidence of the role of microbes in Alzheimer's disease, raising burning questions that need to be addressed to guide therapeutic approaches and potential prophylactic strategies.


Subject(s)
Alzheimer Disease , Humans , Alzheimer Disease/pathology , Alzheimer Disease/therapy , Neurofibrillary Tangles/pathology , Brain , Inflammation/pathology
4.
Trends Neurosci ; 47(4): 259-272, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38508906

ABSTRACT

Middle age has historically been an understudied period of life compared to older age, when cognitive and brain health decline are most pronounced, but the scope for intervention may be limited. However, recent research suggests that middle age could mark a shift in brain aging. We review emerging evidence on multiple levels of analysis indicating that midlife is a period defined by unique central and peripheral processes that shape future cognitive trajectories and brain health. Informed by recent developments in aging research and lifespan studies in humans and animal models, we highlight the utility of modeling non-linear changes in study samples with wide subject age ranges to distinguish life stage-specific processes from those acting linearly throughout the lifespan.


Subject(s)
Brain , Cognition , Middle Aged , Animals , Humans , Aging
5.
Brain ; 146(12): 4916-4934, 2023 12 01.
Article in English | MEDLINE | ID: mdl-37849234

ABSTRACT

Alzheimer's disease is a complex neurodegenerative disorder leading to a decline in cognitive function and mental health. Recent research has positioned the gut microbiota as an important susceptibility factor in Alzheimer's disease by showing specific alterations in the gut microbiome composition of Alzheimer's patients and in rodent models. However, it is unknown whether gut microbiota alterations are causal in the manifestation of Alzheimer's symptoms. To understand the involvement of Alzheimer's patient gut microbiota in host physiology and behaviour, we transplanted faecal microbiota from Alzheimer's patients and age-matched healthy controls into microbiota-depleted young adult rats. We found impairments in behaviours reliant on adult hippocampal neurogenesis, an essential process for certain memory functions and mood, resulting from Alzheimer's patient transplants. Notably, the severity of impairments correlated with clinical cognitive scores in donor patients. Discrete changes in the rat caecal and hippocampal metabolome were also evident. As hippocampal neurogenesis cannot be measured in living humans but is modulated by the circulatory systemic environment, we assessed the impact of the Alzheimer's systemic environment on proxy neurogenesis readouts. Serum from Alzheimer's patients decreased neurogenesis in human cells in vitro and were associated with cognitive scores and key microbial genera. Our findings reveal for the first time, that Alzheimer's symptoms can be transferred to a healthy young organism via the gut microbiota, confirming a causal role of gut microbiota in Alzheimer's disease, and highlight hippocampal neurogenesis as a converging central cellular process regulating systemic circulatory and gut-mediated factors in Alzheimer's.


Subject(s)
Alzheimer Disease , Gastrointestinal Microbiome , Humans , Rats , Animals , Hippocampus , Cognition , Gastrointestinal Microbiome/physiology , Neurogenesis/physiology
6.
Med Sci Educ ; 33(4): 945-953, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37546207

ABSTRACT

Motivation is critical for meaningful learning among healthcare students studying anatomy. Learners are highly variable, and it is important to ensure learners are equally supported in the diverse aspects of an anatomy curriculum. The implementation of the educational framework, Universal Design for Learning (UDL), in anatomy curricula could potentially enhance student motivation. The multiple means of engagement principle of UDL refers to the enhancement of motivation among students. This study aimed to identify healthcare students' motivation levels at the start and end of their anatomy module and whether there was any change in motivation. The Motivated Strategies for Learning Questionnaire (MSLQ) was distributed to gather the self-reported motivation levels of first-year undergraduate medical, dental and occupational therapy (OT) and speech and language therapy (SLT) students studying anatomy at the start of their respective anatomy modules and again at the end of the module. The overall response rate was 74% and 69%, at the start and end of the study, respectively. Responses were analysed by the respective programme of study. Motivation to study anatomy among medical, dental, OT and SLT students ranged from medium to high on the MSLQ at the start of their respective anatomy modules. By the end of the anatomy modules, dental students reported high levels of motivation to study anatomy, whereas motivation among medical, OT and SLT students ranged from medium to high. A change in students' self-reported motivation levels while studying anatomy was identified. The study emphasises the benefits of UDL and its flexible nature to enhance motivation.

8.
Neurosci Biobehav Rev ; 149: 105147, 2023 06.
Article in English | MEDLINE | ID: mdl-36990371

ABSTRACT

Adolescence is a period of biological, psychological and social changes, and the peak time for the emergence of mental health problems. During this life stage, brain plasticity including hippocampal neurogenesis is increased, which is crucial for cognitive functions and regulation of emotional responses. The hippocampus is especially susceptible to environmental and lifestyle influences, mediated by changes in physiological systems, resulting in enhanced brain plasticity but also an elevated risk for developing mental health problems. Indeed, adolescence is accompanied by increased activation of the maturing hypothalamic-pituitary-adrenal axis, sensitivity to metabolic changes due to increased nutritional needs and hormonal changes, and gut microbiota maturation. Importantly, dietary habits and levels of physical activity significantly impact these systems. In this review, the interactions between exercise and Western-style diets, which are high in fat and sugar, on adolescent stress susceptibility, metabolism and the gut microbiota are explored. We provide an overview of current knowledge on implications of these interactions for hippocampal function and adolescent mental health, and speculate on potential mechanisms which require further investigation.


Subject(s)
Hypothalamo-Hypophyseal System , Mental Health , Humans , Adolescent , Pituitary-Adrenal System , Diet , Exercise
9.
Clin Pharmacol Ther ; 113(2): 246-259, 2023 02.
Article in English | MEDLINE | ID: mdl-35278334

ABSTRACT

Depression is considered a major public health concern, where existing pharmacological treatments are not equally effective across all patients. The pathogenesis of depression involves the interaction of complex biological components, such as the immune system and the microbiota-gut-brain axis. Adjunctive lifestyle-oriented approaches for depression, including physical exercise and special diets are promising therapeutic options when combined with traditional antidepressants. However, the mechanisms of action of these strategies are incompletely understood. Accumulating evidence suggests that physical exercise and specific dietary regimens can modulate both the immune system and gut microbiota composition. Here, we review the current information about the strategies to alleviate depression and their crosstalk with both inflammatory mechanisms and the gut microbiome. We further discuss the role of the microbiota-gut-brain axis as a possible mediator for the adjunctive therapies for depression through inflammatory mechanisms. Finally, we review existing and future adjunctive strategies to manipulate the gut microbiota with potential use for depression, including physical exercise, dietary interventions, prebiotics/probiotics, and fecal microbiota transplantation.


Subject(s)
Brain-Gut Axis , Depression , Humans , Depression/therapy , Antidepressive Agents/therapeutic use , Inflammation , Life Style
10.
Anat Sci Educ ; 16(1): 10-26, 2023 Jan.
Article in English | MEDLINE | ID: mdl-34862859

ABSTRACT

There are concerns among healthcare practitioners about poor anatomical knowledge among recent healthcare graduates. Universal Design for Learning (UDL) is a framework developed to enhance students' experience of learning and help students to become motivated learners. This scoping review identified whether UDL has been utilized in third level healthcare education and if so, whether it had been used to enhance student motivation to study anatomy. Seven online databases were searched for studies reporting the use of UDL in the curricula of medical, dental, occupational therapy (OT) or speech and language therapy (SLT) programs. Studies were screened for eligibility with set inclusion criteria. Data were extracted and analyzed. Analysis revealed that UDL was not specifically mentioned in any of the studies thus there are no published studies on UDL being formally applied in healthcare education. However, the authors identified 33 publications that described teaching methods which aligned with UDL in anatomy curricula and a thematic analysis yielded four main themes relating to teaching strategies being employed. Universal design for learning was not mentioned specifically, indicating that educators may not be aware of the educational framework, although they appeared to be utilizing aspects of it in their teaching. The review revealed that there is a lack of research concerning the anatomy education of OT and SLT students. The role of UDL in enhancing motivation to learn anatomy in medical, dental, OT and SLT programs has yet to be explored.


Subject(s)
Anatomy , Universal Design , Humans , Anatomy/education , Learning , Students , Curriculum , Delivery of Health Care
11.
Clin Anat ; 36(1): 137-150, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36069043

ABSTRACT

There is an increasing need to facilitate enhanced student engagement in anatomy education. Higher education students differ in academic preferences and abilities and so, not all teaching strategies suit all students. Therefore, it is suggested that curricula design and delivery adapt to sustain learner engagement. Enhanced learner engagement is a fundamental feature of Universal Design for Learning (UDL). The aim of this study is to determine if anatomy educators in the Republic of Ireland (ROI) and United Kingdom (UK) are aware of UDL and to assess if, and to what extent, it has been implemented in the design and delivery of anatomy curricula for healthcare students. An anonymous online questionnaire was administered to anatomy educators in higher level institutions in the ROI and UK. Inductive content analysis was used to identify the impact of UDL on student learning, engagement, and motivation, as perceived by the participants. The response rate was 23% (n = 61). Nineteen participants stated they knew of UDL. Of these, 15 had utilized UDL in their teaching of anatomy. Analysis indicated that the perception of UDL was mixed. However, the majority of responses relating to UDL were positive. The majority of the respondents were unaware of UDL but identified the frameworks' checkpoints within their curriculum, suggesting they have unknowingly incorporated elements of UDL in their curriculum design and delivery. There is a lack of information on the benefits of explicit utilization of UDL for engagement and motivation to learn anatomy in healthcare programs in the ROI and UK.


Subject(s)
Anatomy , Universal Design , Humans , Learning , Curriculum , Universities , Ireland , United Kingdom , Anatomy/education
12.
Neurobiol Dis ; 170: 105746, 2022 08.
Article in English | MEDLINE | ID: mdl-35526743

ABSTRACT

Temporal lobe epilepsy (TLE) is a neurological disorder affecting millions of people worldwide and currently represents the most common form of focal epilepsy. Thus, the search for aetiological and pathophysiological parameters of TLE is ongoing. Preclinical work and post-mortem human studies suggest adult hippocampal neurogenesis as a potentially relevant factor in TLE pathogenesis. Although progress has been made in elucidating the molecular links between TLE and hippocampal neurogenesis, recent evidence suggests that additional peripheral mediators may be involved. The microbiota-gut-brain axis mediates bidirectional communication between the gut and the brain and could comprise a link between neurogenesis and TLE. In this review, we discuss emerging evidence highlighting a potential role for the gut microbiome in connecting TLE pathogenesis and hippocampal neurogenesis. We focus in particular on mechanisms associated with neuronal excitability, neuroinflammation and gut microbial metabolites. As the evidence does not yet support a direct link between gut microbiota-regulated hippocampal neurogenesis and TLE aetiology or pathophysiology, future studies are needed to establish whether current findings comprise circumstantial links or a potentially novel avenue for clinically relevant research.


Subject(s)
Epilepsy, Temporal Lobe , Epilepsy , Gastrointestinal Microbiome , Adult , Gastrointestinal Microbiome/physiology , Hippocampus/pathology , Humans , Neurogenesis
13.
Anticancer Res ; 42(2): 801-810, 2022 Feb.
Article in English | MEDLINE | ID: mdl-35093878

ABSTRACT

BACKGROUND/AIM: Current treatment strategies for advanced melanoma require serial assessment of disease status in affected patients. In this study, we sought to examine the relationship between radiographic tumour burden and blood borne biomarkers including plasma cfDNA, serum LDH, plasma VEGF, PD-L1 and IFN-γ in advanced melanoma patients receiving immunotherapy. We hypothesized that a combination of these explanatory variables in a suitable regression analysis model may predict changes in tumour burden during patient treatment. MATERIALS AND METHODS: We extracted and quantified circulating cfDNA, LDH, VEGF, PD-L1, and IFN-γ from thirty patients with stage IV melanoma at baseline and at six months. All participating patients were evaluated with paired blood sample collection and CT scan assessments during treatment. RESULTS: Changes in radiographic tumour burden correlated with changes in levels of cfDNA (p≤0.001), LDH (p≤0.001), VEGF (p≤0.001), and PD-L1 (p<0.05) during treatment. Multiple regression analysis consisting of the follow-up to baseline assessment ratios of cfDNA, LDH, VEGF and PD-L1 explained changes in tumour burden (F (4, 23)=32.05, p<0.001); with an R2 of 0.8479 (Y=ß0+ß1*B+ß2*C+ß3*D+ß4*E). CONCLUSION: A quantitative measure of cfDNA, LDH, VEGF and PD-L1 may complement current methods of assessing tumour burden in advanced melanoma patients.


Subject(s)
Melanoma/blood , Melanoma/therapy , Adult , Aged , Aged, 80 and over , B7-H1 Antigen/blood , Biomarkers, Tumor/blood , Cell-Free Nucleic Acids/blood , Female , Humans , Immunotherapy , Interferon-gamma/blood , L-Lactate Dehydrogenase/blood , Male , Melanoma/pathology , Middle Aged , Regression Analysis , Tumor Burden , Vascular Endothelial Growth Factor A/blood
15.
Nutr Neurosci ; 25(4): 657-669, 2022 Apr.
Article in English | MEDLINE | ID: mdl-32723167

ABSTRACT

Introduction: Adolescence is an important stage of maturation for various brain structures. It is during this time therefore that the brain may be more vulnerable to environmental factors such as diet that may influence mood and memory. Diets high in fat and sugar (termed a cafeteria diet) during adolescence have been shown to negatively impact upon cognitive performance, which may be reversed by switching to a standard diet during adulthood. Consumption of a cafeteria diet increases both peripheral and central levels of interleukin-1ß (IL-1ß), a pro-inflammatory cytokine which is also implicated in cognitive impairment during the ageing process. It is unknown whether adolescent exposure to a cafeteria diet potentiates the negative effects of IL-1ß on cognitive function during adulthood.Methods: Male Sprague-Dawley rats consumed a cafeteria diet during adolescence after which time they received a lentivirus injection in the hippocampus to induce chronic low-grade overexpression of IL-1ß. After viral integration, metabolic parameters, circulating and central pro-inflammatory cytokine levels, and cognitive behaviours were assessed.Results: Our data demonstrate that rats fed the cafeteria diet exhibit metabolic dysregulations in adulthood, which were concomitant with low-grade peripheral and central inflammation. Overexpression of hippocampal IL-1ß in adulthood impaired spatial working memory. However, adolescent exposure to a cafeteria diet, combined with or without hippocampal IL-1ß in adulthood did not induce any lasting cognitive deficits when the diet was replaced with a standard diet in adulthood. Discussion: These data demonstrate that cafeteria diet consumption during adolescence induces metabolic and inflammatory changes, but not behavioural changes in adulthood.


Subject(s)
Diet , Spatial Memory , Animals , Brain/metabolism , Diet, High-Fat/adverse effects , Hippocampus/metabolism , Male , Rats , Rats, Sprague-Dawley
16.
Clin Anat ; 35(1): 26-39, 2022 Jan.
Article in English | MEDLINE | ID: mdl-34482575

ABSTRACT

Appropriate anatomy education for speech and language therapists is a crucial part of preparation for clinical practice. While much research has been conducted regarding the anatomical education of medical students, there is a paucity of evidence for speech and language therapy students. This study assessed the methods employed by a cohort of first-year speech and language therapy students to learn anatomy, their perceptions of the clinical importance of anatomy and motivation to learn anatomy (using a modified version of the motivation strategies for learning questionnaire) and how this related to potential barriers to motivation such as mental well-being (using the Warwick-Edinburgh Mental Well-Being Scale [WEMWBS]). Analysis revealed that 92% of students agreed or strongly agreed that a sound knowledge of anatomy is important for clinical practice, 74% agreed or strongly agreed that listening at lectures was how they primarily learned anatomy, and 91% of students agreed or strongly agreed that they worried a great deal about tests. The latter statement was negatively correlated with a number of statements on the WEMWBS. Overall, the data revealed that first-year speech and language therapy students place importance on anatomy and its role in their future clinical practice, that they have different preferences for learning anatomy compared to medical students, and also have significant anxiety surrounding anatomy examinations. Multiple significant correlations between responses to the motivation and mental well-being questionnaires suggest that there is a significant relationship between first-year student motivation to learn anatomy and well-being.


Subject(s)
Anatomy , Education, Medical, Undergraduate , Students, Medical , Anatomy/education , Curriculum , Humans , Learning , Motivation , Surveys and Questionnaires
17.
J Med Food ; 25(9): 924-929, 2022 Sep.
Article in English | MEDLINE | ID: mdl-34185600

ABSTRACT

Middle age is increasingly accepted as a key period during which individuals are susceptible to the effect of environmental and lifestyle factors. Emerging research indicates that dietary factors play a crucial role in brain health and cognitive function, and studies in both animals and humans have demonstrated that dietary interventions can mitigate cognitive impairment. Specifically, magnesium has been shown to enhance learning and memory, and magnesium deficiency is associated with impaired hippocampal-dependent memory formation in animal studies. The aim of this study was to examine if supplementation with a magnesium-rich marine mineral blend (MMB) could alter middle-age-related cognitive impairment. Young and middle-aged rats were given access to a control diet or an experimental diet formulated with an MMB for 4 weeks before undergoing a series of behavioral assessments. Supplementation of MMB to middle-aged rats rescued a deficit in cognitive impairment, specifically a pattern separation paradigm that is sensitive to alterations in a type of brain plasticity called neurogenesis. It had no effect on general activity in the open field or performance on other hippocampal-associated tasks. Changes in cognitive function occur as a predictable consequence of aging. Research into whether modification of dietary factors, such as this MMB, may play a role in the prevention of age-related cognitive impairment warrants further investigation.


Subject(s)
Hippocampus , Magnesium , Aging , Animals , Dietary Supplements , Humans , Memory Disorders , Middle Aged , Minerals , Neurogenesis , Rats
18.
Brain Behav Immun ; 99: 327-338, 2022 01.
Article in English | MEDLINE | ID: mdl-34732365

ABSTRACT

Stress during critical periods of neurodevelopment is associated with an increased risk of developing stress-related psychiatric disorders, which are more common in women than men. Hippocampal neurogenesis (the birth of new neurons) is vulnerable to maternal separation (MS) and inflammatory stressors, and emerging evidence suggests that hippocampal neurogenesis is more sensitive to stress in the ventral hippocampus (vHi) than in the dorsal hippocampus (dHi). Although research into the effects of MS stress on hippocampal neurogenesis is well documented in male rodents, the effect in females remains underexplored. Similarly, reports on the impact of inflammatory stressors on hippocampal neurogenesis in females are limited, especially when female bias in the prevalence of stress-related psychiatric disorders begins to emerge. Thus, in this study we investigated the effects of MS followed by an inflammatory stressor (lipopolysaccharide, LPS) in early adolescence on peripheral and hippocampal inflammatory responses and hippocampal neurogenesis in juvenile female rats. We show that MS enhanced an LPS-induced increase in the pro-inflammatory cytokine IL-1ß in the vHi but not in the dHi. However, microglial activation was similar following LPS alone or MS alone in both hippocampal regions, while MS prior to LPS reduced microglial activation in both dHi and vHi. The production of new neurons was unaffected by MS and LPS. MS and LPS independently reduced the dendritic complexity of new neurons, and MS exacerbated LPS-induced reductions in the complexity of distal dendrites of new neurons in the vHi but not dHi. These data highlight that MS differentially primes the physiological response to LPS in the juvenile female rat hippocampus.


Subject(s)
Maternal Deprivation , Neuroinflammatory Diseases , Animals , Female , Hippocampus , Lipopolysaccharides/pharmacology , Male , Microglia , Neurogenesis/physiology , Neurons , Rats
19.
Behav Brain Res ; 421: 113725, 2022 03 12.
Article in English | MEDLINE | ID: mdl-34929235

ABSTRACT

Stress, particularly during childhood, is a major risk factor for the development of depression. Depression is twice as prevalent in women compared to men, which suggests that biological sex also contributes to depression susceptibility. However, the neurobiology underpinning sex differences in the long-term consequences of childhood stress remains unknown. Thus, the aim of this study was to determine whether stress applied during the prepubertal juvenile period (postnatal day 27-29) in rats induces sex-specific changes in anxiety-like behaviour, anhedonia, and antidepressant-like behaviour in adulthood in males and females. The impact of juvenile stress on two systems in the brain associated with these behaviours and that develop during the juvenile period, the mesocorticolimbic dopaminergic system and hippocampal neurogenesis, were also investigated. Juvenile stress altered escape-oriented behaviours in the forced swim test in both sexes, decreased latency to drink a palatable substance in a novel environment in the novelty-induced hypophagia test in both sexes, and decreased open field supported rearing behavior in females. These behavioural changes were accompanied by stress-induced increases in tyrosine hydroxylase immunoreactivity in the prefrontal cortex of both sexes, but not other regions of the mesocorticolimbic dopaminergic system. Juvenile stress did not impact anhedonia in adulthood as measured by the saccharin preference test and had no effect hippocampal neurogenesis across the longitudinal axis of the hippocampus. These results suggest that juvenile stress has long-lasting impacts on antidepressant-like and reward-seeking behaviour in adulthood and these changes may be due to alterations to catecholaminergic innervation of the medial prefrontal cortex.


Subject(s)
Anxiety/physiopathology , Behavior, Animal/physiology , Depression/physiopathology , Hippocampus/physiology , Neurogenesis/physiology , Prefrontal Cortex/metabolism , Reward , Stress, Psychological/physiopathology , Age Factors , Anhedonia/physiology , Animals , Female , Male , Rats , Rats, Sprague-Dawley , Sex Characteristics
20.
Acta Neurochir (Wien) ; 164(3): 723-735, 2022 03.
Article in English | MEDLINE | ID: mdl-34643804

ABSTRACT

BACKGROUND: Research into the potential utility of plasma-derived circulating cell-free nucleic acids as non-invasive adjuncts to radiological imaging have been occasioned by the invasive nature of brain tumour biopsy. The objective of this study was to determine whether significant differences exist in the plasma transcriptomic profile of glioma patients relative to differences in their tumour characteristics, and also whether any observed differences were representative of synchronously obtained glioma samples and TCGA glioma-derived RNA. METHODS: Blood samples were collected from twenty glioma patients prior to tumour resection. Plasma ccfmRNAs and glioma-derived RNA were extracted and profiled. RESULTS: BCL2L1, GZMB, HLA-A, IRF1, MYD88, TLR2, and TP53 genes were significantly over-expressed in glioma patients (p < 0.001, versus control). GZMB and HLA-A genes were significantly over-expressed in high-grade glioma patients (p < 0.001, versus low-grade glioma patients). Moreover, the fold change of the BCL2L1 gene was observed to be higher in patients with high-grade glioma (p = 0.022, versus low-grade glioma patients). There was positive correlation between the magnitude of fold change of differentially expressed genes in plasma- and glioma-derived RNA (Spearman r = 0.6344, n = 14, p = 0.017), and with the mean FPKM in TCGA glioma-derived RNA samples (Spearman r = 0.4614, n = 19, p < 0.05). There was positive correlation between glioma radiographic tumour burden and the magnitude of fold change of the CSF3 gene (r = 0.9813, n = 20, p < 0.001). CONCLUSION: We identified significant differential expression of genes involved in cancer inflammation and immunity crosstalk among patients with different glioma grades, and there was positive correlation between their transcriptomic profile in plasma and tumour samples, and with TCGA glioma-derived RNA.


Subject(s)
Brain Neoplasms , Cell-Free Nucleic Acids , Glioma , Biomarkers , Brain Neoplasms/pathology , Cell-Free Nucleic Acids/genetics , Glioma/pathology , HLA-A Antigens , Humans , Pilot Projects , RNA , RNA, Messenger
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