Thu, 24 Jul 2008 22:58:13 BST CiteULike: Author Brundin http://www.citeulike.org/author/Brundin CiteULike.org en-gb Copyright © 2004-2008 citeulike.org http://www.citeulike.org/group/5052/article/2764063 <i>Nature reviews. Neuroscience, Vol. 3, No. 12. (December 2002), pp. 932-942.</i> Pathogenesis of Parkinson's disease: dopamine, vesicles and alpha-synuclein. J Lotharius P Brundin doi:10.1038/nrn983 Nature reviews. Neuroscience, Vol. 3, No. 12. (December 2002), pp. 932-942. 2008-05-07T07:00:55-00:00 2002 Nature reviews. Neuroscience 1471-003X 3 12 932 942 2002 dopamine parkinsons --review-- synuclein http://www.citeulike.org/user/schmoutz/article/1900849 <i>Eur Neuropsychopharmacol, Vol. 17, No. 9. (September 2007), pp. 573-579.</i><br /><br />Orexins are neuropeptides selectively expressed in a small number of neurons in the lateral-posterior hypothalamus. We measured orexin-A in the cerebrospinal fluid (CSF) of 66 patients with major depressive disorder (MDD), dysthymia and adjustment disorder after a suicide attempt. Blood samples confirmed that the patients were free from antidepressive and neuroleptic medication at the time of the lumbar punctures. CSF levels of orexin-A were significantly lower in patients with MDD than in patients with adjustment disorder and dysthymia. Orexin correlated significantly with CSF levels of somatostatin, delta sleep inducing peptide-like immunoreactivity (DSIP-LI) and corticotrophin releasing factor (CRF), but not with leptin or vasopressin. Plasma levels of thyroid-stimulating hormone (TSH) were not reduced in MDD patients, and did not correlate with CSF-orexin. Our results suggest that suicidal patients with MDD have distinct neurobiological features, involving compromised levels of hypothalamic peptides regulating the state of arousal. Reduced orexin levels in the cerebrospinal fluid of suicidal patients with major depressive disorder. L Brundin M Björkqvist A Petersén L Träskman-Bendz doi:10.1016/j.euroneuro.2007.01.005 Eur Neuropsychopharmacol, Vol. 17, No. 9. (September 2007), pp. 573-579. 2007-11-12T02:37:28-00:00 2007 Eur Neuropsychopharmacol 0924-977X 17 9 573 579 no-tag http://www.citeulike.org/user/jmaryott/article/1049342 <i>Neuroscience, Vol. 142, No. 3. (27 October 2006), pp. 609-613.</i><br /><br />The relationship between adult hippocampal neurogenesis and cognition appears more complex than suggested by early reports. We aimed to determine if the duration and task demands of spatial memory training differentially affect hippocampal neurogenesis. Adult male rats were trained in the Morris water maze in a reference memory task for 4 days, or alternatively working memory for either 4 or 14 days. Four days of maze training did not impact neurogenesis regardless of whether reference or working memory paradigms were used. Interestingly, 2 weeks of working memory training using a hidden platform resulted in fewer newborn hippocampal neurons compared with controls that received either cue training or no maze exposure. Stress is a well-established negative regulator of hippocampal neurogenesis. We found that maze training in general, and a working memory task in particular, increased levels of circulating corticosterone after 4 days of training. Our study indicates that working memory training over a prolonged period of time reduces neurogenesis, and this reduction may partially be mediated by increased stress. Working memory training decreases hippocampal neurogenesis P Mohapel K Mundt-Petersen P Brundin H Frielingsdorf doi:10.1016/j.neuroscience.2006.07.033 Neuroscience, Vol. 142, No. 3. (27 October 2006), pp. 609-613. 2007-01-18T23:17:19-00:00 2006 Neuroscience 142 3 609 613 neurogenisis spatial-memory http://www.citeulike.org/user/dep/article/566550 <i>J Neurosci, Vol. 25, No. 27. (6 July 2005), pp. 6329-6342.</i><br /><br />Models of Parkinson's disease (PD) based on selective neuronal death have been used to study pathogenic mechanisms underlying nigral cell death and in some instances to develop symptomatic therapies. For validation of putative neuroprotectants, a model is desirable in which the events leading to neurodegeneration replicate those occurring in the disease. We developed a human in vitro model of PD based on the assumption that dysregulated cytoplasmic dopamine levels trigger cell loss in this disorder. Differentiated human mesencephalic neuron-derived cells were exposed to methamphetamine (METH) to promote cytoplasmic dopamine accumulation. In the presence of elevated iron concentrations, as observed in PD, increased cytosolic dopamine led to oxidative stress, c-Jun N-terminal kinase (JNK) pathway activation, neurite degeneration, and eventually apoptosis. We examined the role of the mixed-lineage kinases (MLKs) in this complex degenerative cascade by using the potent inhibitor 3,9-bis[(ethylthio)methyl]-K-252a (CEP1347). Inhibition of MLKs not only prevented FeCl2+/METH-induced JNK activation and apoptosis but also early events such as neurite degeneration and oxidative stress. This broad neuroprotective action of CEP1347 was associated with increased expression of an oxidative stress-response modulator, activating transcription factor 4. As a functional consequence, transcription of the cystine/glutamate and glycine transporters, cellular cystine uptake and intracellular levels of the redox buffer glutathione were augmented. In conclusion, this new human model of parkinsonian neurodegeneration has the potential to yield new insights into neurorestorative therapeutics and suggests that enhancement of cytoprotective mechanisms, in addition to blockade of apoptosis, may be essential for disease modulation. Progressive degeneration of human mesencephalic neuron-derived cells triggered by dopamine-dependent oxidative stress is dependent on the mixed-lineage kinase pathway. J Lotharius J Falsig J van Beek S Payne R Dringen P Brundin M Leist doi:10.1523/JNEUROSCI.1746-05.2005 J Neurosci, Vol. 25, No. 27. (6 July 2005), pp. 6329-6342. 2006-03-28T05:01:40-00:00 2005 J Neurosci 1529-2401 25 27 6329 6342 dopamine parkinsons pathway