Publications by authors named "Linda Brand"

Zebrafish (Danio rerio) represents a complementary pre-clinical model in stress and anxiety research. Conspecific alarm substance (CAS), an alarm pheromone secreted by injured fish, acts as a warning signal and modulates fear responses. Given their schooling nature and that injury precedes CAS release, varying fresh CAS concentrations extracted from different numbers of CAS-donating zebrafish may uniquely influence trauma-related behaviours.

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Traumatic stress exposure increases noradrenaline (NA) release, which contributes to anxiety and impaired risk-appraisal. Guanfacine, a selective alpha-2A adrenergic receptor agonist, has been used to treat stress-related disorders characterised by impaired prefrontal cortex function. By acting on both presynaptic inhibitory autoreceptors and postsynaptic heteroreceptors, guanfacine attenuates stress reactivity and enhances cognition.

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Article Synopsis
  • The study examines the link between brain-immune mechanisms and neurocognitive rigidity in deer mice, particularly focusing on rigid motor stereotypy and systemic inflammation markers like the neutrophil-lymphocyte ratio (NLR).
  • Researchers administered a recombinant human granulocyte colony-stimulating factor (g-CSF) to increase NLR and observed its effects on stereotypical behavior, NLR, and plasma corticosterone levels.
  • Results indicated that NLR and plasma corticosterone levels did not predict stereotypical behavior, and while chronic g-CSF treatment raised NLR and lowered corticosterone, it did not affect stereotypical expressions; more research is needed to understand the potential immune-inflammation role in spontaneous stereotypy.
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Background: An increasing body of research implicates inflammatory processes, including alterations in the neutrophil-lymphocyte ratio (NLR), in the pathophysiology of psychiatric illness. The deer mouse (Peromyscus maniculatus bairdii) is commonly studied for its naturalistic expression of compulsive-like behaviour. Towards future efforts to gain an understanding of how innate and adaptive immune processes might be involved in this model, we aimed to study the effects of pegfilgrastim, a pegylated recombinant human granulocyte colony-stimulating factor (g-CSF) analogue, on the NLR of both male and female deer mice.

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Background: Fluoxetine is present in breast milk, yet it is unclear to what extent it, or its active metabolite, norfluoxetine, reaches the brain of the infant and what the effects of such exposure on neurobiological processes are. We therefore aimed to quantify the concentration of passively administered fluoxetine and norfluoxetine in the whole brains of exposed Flinders sensitive line (FSL) offspring and establish their influence on serotonergic function and redox status.

Methods: Adult FSL dams received fluoxetine (10 mg/kg/day), or placebo for fourteen days, beginning on postpartum day 04.

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During the peripartum period, women are at an increased risk to develop perinatal distress, presenting as symptoms of depression and/or anxiety. Yet, due to practical and ethical restrictions, our understanding of this condition remains limited. Animal studies that focus on the neuropsychiatric mechanisms associated with the postpartum period, often ignore the genetical predisposition factor.

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Objective: Although prescription rates of antidepressants for children and adolescents have increased, concerns have been raised regarding effects on neurodevelopment and long-term outcome. Using a genetic animal model of depression, this study investigated the long-term effects of pre-pubertal administration of fluoxetine (FLX) on depressive-like behaviour in early adulthood, as well as on central monoaminergic response to an acute stressor. We postulated that pre-pubertal FLX will have lasting effects on animal behaviour and monoaminergic stress responses in early adulthood.

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Obsessive-compulsive disorder (OCD) is characterized by recurrent thoughts and repetitive motor actions. Hyposerotonergic signalling in the cortico-striatal circuitry is believed to be central to the pathology of OCD, while many patients only respond to chronic treatment with high dose selective serotonin (5HT) reuptake inhibitors (SSRIs). Confined deer mice spontaneously develop two forms of stereotypy, namely vertical jumping and pattern running.

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Background: Endoscopic polypectomy significantly reduces the incidence of colorectal cancer, but recurrence rates are high, especially for adenomas with advanced histology. The present guidelines recommend re-colonoscopy 3 to 5 years later. Due to limited resources, more precise predictions of adenoma recurrence are required.

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There are conflicting results from behavioural studies regarding whether the activation or inhibition of the cGMP-nitric oxide (NO) pathway induces anxiolytic-like behaviour. Sildenafil, an inhibitor of cGMP-selective phosphodiesterase-5, increases anxiety acutely, but previous evidence suggests that its chronic administration may be anxiolytic, and could involve a cholinergic interaction. We used the Flinders Sensitive Line (FSL) rat, a genetic model of depression that presents with increased anxiety- and depression-like behaviour, to investigate the action of chronic treatment with the PDE5 inhibitors sildenafil or tadalafil, with/without atropine on social interaction behaviour, a correlate for anxiety.

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Rationale, Aims And Objectives: To evaluate asthma management and control in primary care clinics so as to design improvements based on guideline-directed outcomes.

Methods: In this study, all medical records of asthma-diagnosed patients (children as well as adults, entire lifespan, asthma-related visits or not) were retrospectively reviewed as a basis for assessing the level of guideline adherence and asthma control. Six primary health care clinics were visited in the Dr Kenneth Kaunda Municipal District, Potchefstroom, South Africa during May to July 2008, 2009 and 2010.

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Surveillance colonoscopy is an important strategy for prevention of colorectal cancer. 5-aminosalicylate (ASA) (mesalazine) is discussed as a chemopreventive agent as it reduces the cancer risk in ulcerative colitis patients. The current study analyses the effect of 5-ASA on Wnt/β-catenin signaling in vitro and in vivo in colon epithelial cells.

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Article Synopsis
  • Patients who have a specific type of medical treatment called allo-HCT need to be watched closely for 90 days after the procedure.
  • Low levels of a protein called serum albumin at day 90 can mean patients are more likely to have serious health problems or die, especially those who had leukemia or a blood disorder.
  • Researchers found that having low serum albumin and poor health scores at that time can help predict who is at greater risk of complications after treatment.
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We explored the antidepressant-like properties of two phosphodiesterase type 5 (PDE5) inhibitors in a genetic animal model of depression, namely Flinders sensitive line rats. We investigated the dose-dependency of the antidepressant-like action of sildenafil, and its interaction with the cholinergic system and behavioural correlates of monoaminergic neurotransmission, in the forced swim test. Antidepressant-like properties of tadalafil (a structurally distinct PDE5 inhibitor) were also evaluated.

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Ampakines have shown beneficial effects on cognition in selected animal models of learning. However, their ability to modify long-term spatial memory tasks has not been studied yet. This would lend credence to their possible value in treating disorders of cognition.

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Symptoms of posttraumatic stress disorder are often precipitated by sensory cues in the form of visual, auditory, olfactory and gustatory "flashbacks" resulting in enhanced fear-memory consolidation and the characteristic symptoms of re-experiencing, avoidance and hyper-arousal. Single prolonged stress with and without re-stress have been used to explore the neurobiology of this disorder, particularly with respect to contextual conditioning and spatial memory impairment. However, less work has been done regarding associative sensory-related memories linked to aversive events.

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Tianeptine, an atypical antidepressant patented and developed by Servier, enhances the synaptic reuptake of serotonin, without affecting norepinephrine and dopamine uptake, while it lacks affinity for neurotransmitter receptors. This mechanism for an antidepressant is apparently paradoxical, since the currently employed antidepressants enhance serotonin by inhibiting its breakdown or by inhibiting monoaminergic reuptake. Although tianeptine has been shown to reduce central 5HT availability and to indirecty modulate central adrenergic and dopaminergic systems and to indirectly inhibit cholinergic hyperactivity, its antidepressant action is believed to be more directly related to central neuronal remodeling and restoration of neuronal plasticity.

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Maternal separation in non-human primates has been proposed as a model of early adversity. The symptoms of separation anxiety were studied in vervet monkeys, during the weaning period, when psychotropic medications were administered. The control group received a normal diet and treatment groups received citalopram, reboxetine or lamotrigine in their food daily.

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Post-traumatic stress disorder (PTSD) is characterized by monoaminergic and hypothalamic-pituitary-adrenal (HPA)-axis abnormalities. Understanding monoamine-HPA-axis responses following stress and restress may provide a greater understanding of the neurobiology of PTSD and of its treatment. Hippocampal and frontal cortex serotonin, noradrenaline and dopamine, plasma corticosterone and aversive behavior were studied in rats on day 1 and day 7 post acute stress (AS = sequential restraint stress, swim stress and halothane exposure), and on day 1 and day 7 post restress (RS = swim stress).

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Structural hippocampus and prefrontal cortex changes occur in patients with posttraumatic stress disorder (PTSD) that appears correlated with cognitive dysfunction. In these brain regions, serotonin (5HT) plays a prominent role in symptom presentation and treatment of PTSD. However, 5HT is both anxiogenic and anxiolytic, and while 5HT reuptake inhibitors are effective in treatment, the role of 5HT in the development of PTSD remains uncertain.

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Rationale: Stress-related glucocorticoid and glutamate release have been implicated in hippocampal atrophy evident in patients with post-traumatic stress disorder (PTSD). Glutamatergic mechanisms activate nitric oxide synthase (NOS), while gamma-amino-butyric acid (GABA) may inhibit both glutamatergic and nitrergic transmission. Animal studies support a role for NOS in stress.

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Post traumatic stress disorder (PTSD) is characterised by hyperarousal, anxiety and amnesic symptoms. Deficits in explicit memory recall have been causally related to volume reductions of the hippocampus and prefrontal cortex. While stress-related glucocorticoid secretion appears involved in this apparent atrophy, there is also evidence for low plasma cortisol in PTSD.

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Abrupt antidepressant withdrawal after chronic treatment is associated with a stress response that may negatively affect the long-term outcome of depression, the neurochemical correlates, of which, remain undetermined. Prolonged depression involves the stress-related release of glucocorticoids and glutamate, while response to antidepressants involves gamma-amino butyric acid (GABA) and the glutamate N-methyl-D-aspartate (NMDA) receptor. Here, imipramine (IMI) was administered to rats for three weeks followed by acute withdrawal for seven days.

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