| 1. |
- Amandusson, Åsa, 1974-, et al.
(författare)
-
Estrogen-induced alterations of spinal cord enkephalin gene expression
- 1999
-
Ingår i: Pain. - : Elsevier. - 0304-3959 .- 1872-6623. ; 83:2, s. 243-248
-
Tidskriftsartikel (refereegranskat)abstract
- Enkephalin-synthesizing neurons in the super®cial laminae of the spinal and trigeminal dorsal horn are critical components of the endogenous pain-modulatory system. We have previously demonstrated that these neurons display intracellular estrogen receptors, suggesting that estrogen can potentially influence their enkephalin expression. By using Northern blot, we now show that a bolus injection of estrogen results in a rapid increase in spinal cord enkephalin mRNA levels in ovariectomized female rats. Thus, 4 h after estrogen administration the enkephalin mRNA-expression in the lumbar spinal cord was on average 68% higher (P , 0:05) than in control animals injected with vehicle only. A small increase in the amount of enkephalin mRNA was also seen after 8 h (P , 0:05), whereas no difference between estrogen-injected and control animals was found after 24 h or at time periods shorter than 4 h. Taken together with the previous anatomical data, the present findings imply that estrogen has an acute effect on spinal opioid levels in areas involved in the transmission of nociceptive information.
|
|
| 2. |
- Amandusson, Åsa, 1974-
(författare)
-
Estrogen receptor expression in relation to pain modulation and transmission : experimental studies in rats
- 2009
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Estrogens have a remarkably wide range of actions in the mammalian brain. They not only play a pivotal role in reproductive behavior and sexual differentiation, but also contribute to e.g. thermoregulation, feeding, memory, neuronal survival and the perception of somatosensory stimuli. A multitude of studies on both animals and human subjects has demonstrated potential effects of gonadal hormones, such as estrogens, on pain transmission. These effects most likely involve multiple neuroanatomical circuits as well as diverse neurochemical systems and therefore need to be evaluated specifically in relation to the localization and intrinsic characteristics of the neurons engaged. The overall aim of this thesis is to gain specific knowledge of the possible cellular mechanisms by which estrogens may influence the transmission of nociceptive stimuli at the level of the spinal cord. The estrogen receptors, by which estrogens regulate non-genomic as well as genomic mechanisms, are crucial to estrogen signaling in general and essential to the estrogen-induced effects in the brain. In Paper I, we use immunohistochemistry to label neurons containing estrogen receptor-! (ERα) in the medullary and spinal dorsal horn of female rats. Large numbers of ER!-expressing neurons were found in lamina I and lamina II, i.e. in the areas involved in the processing of primary afferent nociceptive information. This distribution in part overlaps that of enkephalin, a potent pain-inhibiting endogenous opioid. The effects of gonadal hormones on pain modulation may, to a great extent, be blocked by the opioid antagonist naloxone, suggesting an involvement of the endogenous opioid system in the prosecution of hormonal pain regulation. By combining immunohistochemical labeling of ERα with in situ hybridization of preproenkephalin mRNA (Paper II), we demonstrate that the majority of enkephalinergic neurons in the superficial laminae of the spinal and medullary dorsal horn express ER!. This co-localization and the fact that the preproenkephalin gene contains a sequence that binds ERs, suggest that estrogens may potentially regulate enkephalin expression in these cells. This is further supported by the findings in Paper III in which we show that a single subcutaneous injection of estradiol induces a significant increase (on average 68%) in preproenkephalin mRNA content in the spinal cord after 4 hours. The expression of the enkephalin gene in the spinal cord is thus sensitive to fluctuating estradiol levels. In Paper IV, a noxious injection of formalin is used to induce activation of a neuronal population involved in nociceptive transmission from the face. By using a dual-labeling immunohistochemistry protocol, we were able to identify ER!-expressing cells within this neuronal population suggesting that nociceptive-responsive neurons in the medullary dorsal horn express ER!. In all, our findings provide morphological as well as biochemical evidence in support for an estrogen-dependent modulation of nociceptive processing at the level of the dorsal horn.
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
- Syk, Mikaela, 1990-, et al.
(författare)
-
Biological markers for CNS damage in a patient cohort with suspected autoimmune psychiatric disease
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Background: This study describes the prevalence of CNS damage biomarkers and other CNS pathology in a psychiatric patient cohort enriched for clinical red flags of suspected autoimmune psychiatric disease. The study further explores how CNS damage biomarkers relate to clinical red flags and psychiatric features. Methods: 127 patients were included in the study. A routine cerebrospinal fluid (CSF) analysis was performed and anti-neuronal antibodies were measured. CNS damage biomarkers (neurofilament light chain protein (NfL), glial fibrillary acidic protein (GFAp) and total Tau (t-Tau)) in CSF were related to proposed clinical red flags for autoimmune psychiatric disease, other psychiatric features and MRI and EEG findings. Results: Twenty-seven per cent had elevated levels of CNS damage biomarkers and 21% had basic CSF analysis alterations. Six per cent had anti-neuronal antibodies in serum and 2% in CSF. Fifty percent of patients examined with MRI (n=88) had signs of atrophy and 41% had white matter changes. Twenty-five percent of patients with EEG recordings (n=70) had pathological EEG findings. Elevated NfL, GFAp and t-Tau levels were associated with the presence of clinical red flags. Elevated GFAp and t-Tau were also associated with higher psychiatric symptom ratings.Conclusions: Pre-selection based on clinical red flags for autoimmune psychiatric disease identifies a population where 27% have CSF signs of CNS tissue damage, 21% have CSF alterations suggesting neuroinflammation or blood-brain barrier dysfunction and 6% have anti-neuronal antibodies. Moreover, pathological levels of NfL, GFAp or t-Tau in CSF may be related to distinctive red flags and patterns of psychiatric manifestations.
|
|
