Loss of locus coeruleus noradrenergic neurons alters the inflammatory response to LPS in substantia nigra but does not affect nigral cell loss

This is the accepted version of the following article: Mahmoud M. Iravani, Mona Sadeghian, Sarah Rose and Peter Jenner, “Loss of locus coeruleus noradrenergic neurons alters the inflammatory response to LPS in substantia nigra but does not affect nigral cell loss”, Journal of Neural Transmission, Vol. 121(12): 1493-1505, first published online 30 April 2014. The version of record is available online via doi: 10.1007/s00702-014-1223-1. © Springer-Verlag Wien 2014In Parkinson's disease (PD), destruction of noradrenergic neurons in the locus coeruleus (LC) may precede damage to nigral cells and subsequently exaggerate dopaminergic cell loss. We examine if destruction of the locus coeruleus with N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) alters dopaminergic cell loss in substantia nigra (SN) initiated by lipopolysaccharide (LPS) in the rat through an effect on glial cell activation. In rats, a single intraperitoneal dose of DSP-4 administered 8 days previously, caused a marked loss of tyrosine hydroxylase positive neurons in LC but no change in dopaminergic cell number in SN. Unilateral nigral LPS administration resulted in marked dopaminergic cell death with reactive microgliosis associated with enhanced p47 phox in OX-6 and OX-42 positive microglia. There was proliferation of inducible nitric oxide synthase (iNOS)-positive cells, formation of 3-nitrotyrosine (3-NT) and proliferation of astrocytes that expressed glial cell line-derived neurotrophic factor (GDNF). Following combined DSP-4 treatment and subsequent administration of LPS, unexpectedly, no further loss of tyrosine hydroxylase (TH)-immunoreactivity (-ir) occurred in the SN compared to the effects of LPS alone. However, there was a marked alteration in the morphology of microglial cell and a reduction of 3-NT- and iNOS-ir was evident. Expression of p47 phox was downregulated in microglia but up-regulated in TH-ir neurons. No further change in GFAP-ir was observed compared to that produced by DSP-4 alone or LPS alone, but the expression of GDNF was markedly reduced. This study suggests that in contrast to previous reports, prior LC damage does not influence subsequent nigral dopaminergic cell degeneration induced by LPS. Rather it appears to attenuate the microglial response thought to contribute to disease progression in PD.Peer reviewedFinal Accepted Versio

Different applications of concept maps in Higher Education

Purpose: The aim of this work is to show different applications of concept maps in higher education, concretely in qualifications of the Polytechnic University of Valencia. Design/methodology/approach: Different methodologies have been used depending on the application of concept maps: as evaluation tool, as knowledge organizing tool, and as meaningful learning tool. Findings: Students consider the concept maps useful principally to select key ideas, to achieve a comprehensive view of the lesson, and to bring up the subject. Moreover, concept maps promote the meaningful and active learning, help students to understand, follow-up, and learn subjects with a high load of contents. Research limitations/implications: The most important limitation is the use of the concept maps in subjects with a high number of students. Practical implications: The realization of concept maps allows the student to develop generic competences. Originality/value: The originality of this work is to show how a same tool can be used in different subjects of different qualifications. © Journal of Industrial Engineering and Management, 2011.Bes Piá, A.; Blasco-Tamarit, E.; Muñoz Portero, MJ. (2011). Different applications of concept maps in Higher Education. Journal of Industrial Engineering and Management. 4(1):81-102. doi:10.3926/jiem.2011.v4n1.p81-102Senia811024

Effect of frequency of stimulation on neurogenic responses of isolated rat epidymal vas deferens

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Effects of amphetamine on carrier-mediated and electrically stimulated dopamine release in slices of rat caudate-putamen abd nucleus-accumbens

The effects of (+)-amphetamine on carrier-mediated and electrically stimulated dopamine release were investigated using fast cyclic voltammetry in rat brain slices incorporating the nucleus accumbens, and in the caudate putamen. In the caudate putamen, dopamine release either increased with increasing frequency of local electrical stimulation (hot spots) or did not increase significantly (cold spots); dopamine release increased with increasing frequency of electrical stimulation in the nucleus accumbens. Local pressure application of(+)-amphetamine from a micropipette caused dopamine efflux at all sites examined, and this was not affected by sulpiride, indicating that efflux of dopamine caused by (+)amphetamine is not regulated by dopamine D-2 autoreceptors. (+)-Amphetamine reduced single-pulse electrically stimulated dopamine release at all sites; sulpiride reversed this decrease, indicating that endogenous dopamine released by (+)-amphetamine activates dopamine D-2 autoreceptors. In nucleus accumbens and hot spots, (+)-amphetamine did not affect 20-pulse 50-Hz-stimulated dopamine release, whereas in cold spots it potentiated 20-pulse 50-Hz-stimulated dopamine release. We conclude th at (+)-amphetamine modifies electrically stimulated dopamine release by uptake inhibition or by indirect activation of D-2 autoreceptors; the precise mechanism is determined by site and duration of electrical stimulation.Peer reviewe

Real-time effects of N-methyl-D-aspartic acid on dopamine release in slices of rat caudate putamen : A study using fast cyclic voltammetry

The functional role of N-methyl-D-aspartic acid (NMDA) glutamate receptors in the real-time regulation of single electrical pulse (1 p)-stimulated endogenous dopamine release was investigated in slices of rat caudate putamen using fast cyclic voltammetry at a carbon fibre electrode. In the presence of Mg2+, 20 mu M NMDA had a weak effect on background signals but did not affect 1 p-stimulated dopamine release. Removal of Mg2+ increased the background and doubled 1 p-stimulated dopamine release. In the absence of Mg2+, 20 mu M NMDA caused a transient ''release'' of dopamine and decreased the background signal. The 1 p-stimulated dopamine release was subsequently reduced. In the presence of 1 mu M (+/-)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP), superfusion with 20 mu M NMDA did not cause a transient ''release'' of dopamine, and 1 p-stimulated dopamine release was not subsequently attenuated. In the presence of 1 mu M tetrodotoxin, 1 p-stimulated dopamine release was abolished, but 20 mu M NMDA still caused a transient ''release'' of dopamine. Removal of Ca2+ from the artificial CSF abolished 1 p-stimulated dopamine release and resulted in a decline in the baseline but did not affect dopamine ''release'' when 20 mu M NMDA was added, The dopamine release-inducing effect of 20 mu M NMDA was less pronounced in sites in the caudate putamen where dopamine release increased with frequency of electrical stimulation (hot spots) than in sites where there was little frequency-dependent dopamine release (cold spots). Subsequent 1 p-stimulated dopamine release was less attenuated in cold spots than in hot spots. We conclude that in the absence of Mg2+, NMDA induces release of dopamine by acting at CPP-sensitive NMDA receptors in a Ca2+-independent manner. This transient release depletes dopamine from a storage site from which dopamine is released by 1 p electrical stimulation. These real-time observations of the effects of NMDA on electrical stimulus-independent and -dependent dopamine release may explain the apparently conflicting observations of the effects of NMDA on dopamine release made in previous studies, They also indicate that dopamine release and storage are heterogeneous at different sites in the rat caudate putamen.Peer reviewe

Comparison of somatodendritic and axon terminal dopamine release in the ventral tegmental area and the nucleus accumbens

Fast cyclic voltammetry at a carbon fibre microelectrode was used to measure dopamine release following electrical or chemical stimulation in rat brain slices incorporating either the ventral tegmental area or the core region of the nucleus accumbens. Electrical or chemical stimulation gave clear voltammetric signals which corresponded to dopamine; less dopamine was released in the ventral tegmental area than in the nucleus accumbens. In contrast to the nucleus accumbens, electrically stimulated dopamine release in the ventral tegmental area was not sensitive to tetrodotoxin, was not modified by the presence of dopamine uptake inhibitors, or agonist or blockers acting at dopamine D-2 autoreceptors.Peer reviewe

Striatal plasticity in Parkinson's disease and L-DOPA induced dyskinesia

Striatal function adapts to the loss of nigrostriatal dopaminergic input in Parkinson's disease (PD) to initially maintain voluntary movement, but subsequently changes in response to drug treatment leading to the onset of motor complications, notably dyskinesia. Alterations in presynaptic dopaminergic function coupled to changes in the response of post-synaptic dopaminergic receptors causing alterations in striatal output underlie attempts at compensation and the control of movement in early PD. However, eventually compensation fails and persistent changes in striatal function ensue that involve morphological, biochemical and electrophysiological change. Key alterations occur in cholinergic and glutamatergic transmission in the striatum and there are changes in motor programming controlled by events involving LTP/LTD. Dopamine replacement therapy with L-DOPA modifies altered striatal function and restores motor function but non-physiological dopamine receptor stimulation leads to altered signalling through D1 and D2 receptor systems and changes in striatal function causing abnormalities of LTP/LTD mediated through glutamatergic/nitric oxide (NO) mechanisms. These lead to the onset of dyskinesia and underlie the priming process that characterise dyskinesia and its persistence.Peer reviewe