29 research outputs found
Rapid ascent of rhyolitic magma at Chaitén volcano, Chile
International audienceAlthough rhyolite magma has fuelled some of the Earth's largest explosive volcanic eruptions, our understanding of these events is incomplete due to the previous lack of direct observation of these eruptions. On 1 May 2008, Chaitén volcano in Chile erupted rhyolite magma unexpectedly and explosively. Here, petrological and experimental data are presented that indicate that the hydrous rhyolite magma at Chaitén ascended very rapidly from storage depth to near-surface, with velocities of the order of one metre per second
Evidence for a distinct neuro-immune signature in rats that develop behavioural disability after nerve injury
Altered Thyroid Hormone Regulation and Behavioural Change in a Sub-population of Rats following Injury
Overview Of This Thesis. This thesis documents an investigation of thyroid hormones and the regulation of thyroid hormones in an animal model of neuropathic pain. The technique used in this model, Chronic Constriction Injury (CCI), produces an injury that creates an inescapable mechanical and inflammatory stress for the rat. Various forms of stress, and in particular unavoidable stress, have been shown to alter thyroid hormones in both rats and humans. This rat model has been developed to more closely resemble the neuropathic pain state in humans where a proportion of patients develop a syndrome of social and behavioural changes, which has been termed ‘disability’. As well as demonstrable sensory dysfunction, as a result of the nerve injury, a sub-population of the rats exhibit altered patterns of complex social behaviours. The results of three experiments are presented. In each case a cohort of rats was subjected to the same procedure – Chronic Constriction Injury – and changes in social behaviour measured using a Resident-Intruder test. Rats were assigned to one of three groups based on the results of the behavioural test: No Disability (ND), Transient Disability (TD) or Persistent Disability (PD). In experiment 1, documented in Chapter 4, peripheral thyroid and corticosteroid hormones were measured pre and post-CCI together with Thyroid Stimulating Hormone (TSH) levels. Results for the three different behavioural groups were compared. In experiment 2, documented in Chapter 5, RNA was extracted from the hypothalamuses of rats sacrificed six days post CCI. Relative gene expression was determined for a number of factors involved in thyroid hormone and corticosteroid regulation. In experiment 3, documented in Chapter 6, at the end of the experimental period, seven days post-CCI, the rats were perfused to remove blood and the brains preserved in paraformaldehyde. The hypothalamuses were examined using immunohistochemical techniques for evidence of differing protein expression for molecules involved in thyroid hormone regulation. Summary of Findings. Behavioural Testing (Chapter 3): The results of behavioural testing for the experimental groups of animals used in this study conform to those previously found using this model (Monassi et al., 2003). Based on previously derived criteria 70% were classified as ‘No Disability’ (ND); 10% of the rats and were classified as ‘Transient Disability’ (TD) and 20% of rats were classified as ‘Permanent Disability’ (PD) animals. Rats classified as PD have significantly decreased levels of Dominance behaviour on days 1-3 and 4-6 post-CCI when compared to ND rats whereas TD rats have decreased Dominance behaviour on days 1-3 only. Pre-CCI behaviour is not predictive of post-CCI behavioural change. Peripheral Thyroid Hormones (Chapter 4): When compared to pre-injury levels, the mean total thyroxine (TT4), total triiodothyronine (TT3) and free thyroxine (fT4) levels were significantly decreased in the PD rats whereas the post-injury levels of these hormones did not change in the ND and TD rats. There was no difference between groups in mean free triiodothyronine (fT3) and thyroid stimulating hormone (TSH) levels pre and post-injury. The pattern of secretion of hormones differed in the ND and PD rats over the six days post-injury. In the ND rats, there was a surge in TSH post-injury and thyroid hormone levels were maintained at pre-injury levels. However, in the PD group, the TSH response was delayed, blunted and inadequate as thyroid hormone levels decreased. There was a significant correlation between decreased Dominance behaviour and both TT4 and fT4 but no correlation with TT3 or fT3. Peripheral Corticosteroids (Chapter 4): There was an increase in corticosterone in all animals post-CCI. The Transient Disability rats showed the greatest increase in corticosteroid and this was significantly different to the other two groups of rats. There was no difference in post-CCI corticosterone levels between the PD and ND rats. Hypothalamo-pituitary-thyroid (HPT Axis) regulation (Chapters 5 & 6): RT-qPCR measurement of relative mRNA expression in the hypothalamus showed that there was no difference between No Disability, Transient Disability and two groups of control rats (Behavioural Controls (BC) and naïve group caged controls) for Thyrotrophin Releasing Hormone (TRH), Thyroid Hormone Receptor β (TR β), Deiodinase 2 (Dio2) and Deiodinase 3 (Dio3). Compared to the BC rats, the Permanent Disability rats had significantly decreased relative expression of TRH and Deiodinase 2 and significantly increased expression of Deiodinase 3 mRNA. Immunohistochemical techniques used to label TRH, TR β, Deiodinase2 and Deiodinase 3 protein distribution in the Paraventricular Nucleus (PVN) of the hypothalamus showed significantly fewer immunoreactive profiles for Deiodinase 3 and TRβ in the group with changed behaviour (PD group) compared to the Behavioural Control rats. These differences were shown to be specific for the sections of the PVN where the hypophysiotrophic TRH secreting neurons are known to be primarily located. Hypothalamo-pituitary-adrenal (HPA axis) regulation (Chapter 5): RT-qPCR measurement of relative mRNA expression in the hypothalamus showed that there was no difference between ND, TD, PD and Behavioural Controls rats for Corticotrophin Releasing Hormone (CRH), Glucocorticoid Receptor (GR) and Vasopressin. Compared to the Behavioural Controls, group caged Control animals had significantly increased relative expression of CRH and Vasopressin mRNA
Rats with altered behaviour following nerve injury show evidence of centrally altered thyroid regulation
The co-morbidity of mood disturbance, in a proportion of patients, is now described across a wide range of chronic disease states. Similarly, a ‘Low Thyroid Syndrome’ is also reported in a proportion of individuals with chronic diseases. Here, we report on central changes in an animal model of inflammatory stress in which altered social behaviour, representing social disability, persists in a sub-group of rats following injury. We showed in an earlier study that rats with social disability following injury have significantly decreased peripheral thyroid hormones, with no increase in Thyroid Stimulating Hormone (TSH). Only rats identified by behavioural change showed changes in hypothalamic gene expression. In whole hypothalamus extracted RNA, relative expression of mRNA for Thyrotrophin-releasing hormone (TRH) was significantly down-regulated in disabled rats (p = 0.039) and deiodinase 3 up-regulated (p = 0.006) compared to controls. Specifically in the paraventricular nucleus (PVN), numbers of immunoreactive cells for deiodinase 3-like and thyroid hormone receptor beta-like proteins were decreased in the sub-group with disability compared to the control group (p = 0.031 and p = 0.011 respectively). In rats with behavioural change post-injury, down-regulation of TRH provides an explanation for the failure of the hypothalamo-pituitary-thyroid (HPT) axis to respond to the post-injury decrease in thyroxine. Decreased local expression of deiodinase 3 protein, resulting in a local increase in T3, offers an explanation for down regulation of TRH in the hypophysiotrophic TRH neurons. It is possible that, in a sub-group of animals identified behaviourally, a mechanism resulting in hypothalamic down-regulation of the HPT axis persists following inflammatory injury. © 2014 Elsevier B.V
Altered thyroid hormones and behavioural change in a sub-population of rats following chronic constriction injury.
Hypothyroidism is associated with a disturbance of behaviour and mood. There are also individuals, not classified as hypothyroid, with low to ‘low normal’ thyroid hormone levels and normal thyroid-stimulating hormone (TSH) levels who have mood and behavioural changes. As the peripheral thyroid hormones decrease, TSH is expected to increase. However, there are a number of physiological mechanisms known to suppress TSH. In the present study, we report on thyroid hormone regulation in a rat model of neuropathic pain and altered social behaviour that is usually transient, but is persistent in a sub-group of the population. Following ligation of the sciatic nerve, male Sprague-Dawley rats were assessed for social dominance towards an intruder: 20% showed persistently decreased social dominance. Plasma levels of thyroid hormones, TSH and corticosterone were measured before and on days 2, 3, 4, 5 and 6 after injury in 21 rats. The mean plasma thyroxine (T4), free thyroxine (fT4) and triiodothyronine (T3) levels decreased significantly post-injury in rats with persistently changed behaviour compared to rats with unchanged behaviour (P ≤ 0.002). There was no significant difference between groups for mean change in free triiodothyronine (fT3) or TSH. There was a correlation between decreased dominance behaviour and decrease in both T4 (r = 0.62, P = 0.009) and fT4 (r = 0.71, P = 0.001), but no correlation with TSH. In a sub-population of rats, decreased thyroid hormones did not result in the expected increased levels of TSH to restore pre-injury levels, nor did they show increased hypothalamic thyrotrophin-releasing hormone mRNA expression, indicating altered hypothalamic-pituitary-thyroid axis regulation. Because T3 availability to the brain is dependent on both circulating T3 and T4, decreased peripheral thyroid hormones may result in changed neural function, as expressed in altered complex behaviours in this sub-population of rats. © 2010, Wiley-Blackwell