Journal of neuroendocrinology
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J. Neuroendocrinol. · Jan 2012
Selective oestrogen receptor modulators differentially potentiate brain mitochondrial function.
The mitochondrial energy-transducing capacity of the brain is important for long-term neurological health and is influenced by endocrine hormone responsiveness. The present study aimed to determine the role of oestrogen receptor (ER) subtypes in regulating mitochondrial function using selective agonists for ERα (propylpyrazoletriol; PPT) and ERβ (diarylpropionitrile; DPN). Ovariectomised female rats were treated with 17β-oestradiol (E(2) ), PPT, DPN or vehicle control. ⋯ Furthermore, lipid peroxides, accumulated as a result of hormone deprivation, were significantly reduced by E(2) , PPT and DPN. These findings suggest that the activation of both ERα and ERβ is differentially required to potentiate mitochondrial function in brain. As active components in hormone therapy, synthetically designed oestrogens as well as natural phyto-oestrogen cocktails can be tailored to improve brain mitochondrial endpoints.
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J. Neuroendocrinol. · Jan 2012
ReviewTranslocator protein (18 kDa) as a target for novel anxiolytics with a favourable side-effect profile.
Anxiety disorders are frequent and highly disabling diseases with considerable socio-economic impact. In the treatment of anxiety disorders, benzodiazepines (BZDs) as direct modulators of the GABA(A) receptor are used as emergency medication because of their rapid onset of action. However, BZDs act also as sedatives and rather quickly induce tolerance and abuse liability associated with withdrawal symptoms. ⋯ Also in humans, XBD173 displays antipanic activity and does not cause sedation and withdrawal symptoms after 7 days of treatment. XBD173 therefore appears to be a promising candidate for fast-acting anxiolytic drugs with less severe side-effects than BZDs. In this review, we focus on the pathophysiology of anxiety disorders and TSPO ligands as a novel pharmacological approach in the treatment of these disorders.
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J. Neuroendocrinol. · Sep 2011
Triiodothyronine administration ameliorates the demyelination/remyelination ratio in a non-human primate model of multiple sclerosis by correcting tissue hypothyroidism.
Remyelination failure is a key landmark in chronic progression of multiple sclerosis (MS), the most diffuse demyelinating disease in human, but the reasons for this are still unknown. It has been shown that thyroid hormone administration in the rodent models of acute and chronic demyelinating diseases improved their clinical course, pathology and remyelination. ⋯ We also found that severely ill animals display hypothyroidism and severe alteration of deiodinase and thyroid hormone receptor mRNAs expression in the spinal cord, which was completely corrected by thyroid hormone treatment. We therefore suggest that thyroid hormone treatment improves myelin sheath morphology in marmoset EAE, by correcting the dysfunction of thyroid hormone cellular effectors.
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J. Neuroendocrinol. · Jul 2011
Developmental changes in the sexually dimorphic expression of secretory carrier membrane protein 1 and its co-localisation with androgen receptor protein in the zebra finch song system.
The song system of zebra finches differs dramatically between the sexes in terms of both structure and function. Only males sing and the brain regions regulating the learning and production of this behaviour are far more developed in males than females. Mechanisms regulating sexual differentiation likely include both direct genetic and hormonal processes. ⋯ Almost all SCAMP1 cells co-expressed AR and approximately half of the AR cells expressed SCAMP1 in the HVC and robust nucleus in the arcopallium (RA) of both sexes and in the Area X of males (which could not be clearly defined in females). In HVC and RA, more single and double-labelled cells were detected in males than females overall, and the sex differences increased as animals matured. The results suggest the potential for interaction of these two proteins in regulating development of brain and/or behaviour.
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J. Neuroendocrinol. · Jul 2011
Palmitoylethanolamide stimulation induces allopregnanolone synthesis in C6 Cells and primary astrocytes: involvement of peroxisome-proliferator activated receptor-α.
Palmitoylethanolamide (PEA) regulates many pathophysiological processes in the central nervous system, including pain perception, convulsions and neurotoxicity, and increasing evidence points to its neuroprotective action. In the present study, we report that PEA, acting as a ligand of peroxisome-proliferator activated receptor (PPAR)-α, might regulate neurosteroidogenesis in astrocytes, which, similar to other glial cells and neurones, have the enzymatic machinery for neurosteroid de novo synthesis. Accordingly, we used the C6 glioma cell line and primary murine astrocytes. ⋯ Moreover, PEA showed a protective effect, reducing malondialdehyde formation in cells treated with l-buthionine-(S,R)-sulfoximine, a glutathione depletor and, interestingly, the effect of PEA was partially inhibited by finasteride, a 5α-reductase inhibitor. A similar profile of activity was demonstrated by ALLO and the lack of an additive effect with PEA suggests that the reduction of oxidative stress by PEA is mediated through ALLO synthesis. The present study provides evidence indicating the involvement of the saturated acylethanolamide PEA in ALLO synthesis through PPAR-α in astrocytes and explores the antioxidative activity of this molecule, confirming its homeostatic and protective role both under physiological and pathological conditions.