Exposure to static magnetic field facilitates selective attention and neuroplasticity in rats.

Static magnetic fields (SMF) have neuroprotective and behavioral effects in rats, however, little is known about the effects of SMF on cognition, motor function and the underlying neurochemical mechanisms. In this study, we focused on the effects of short-term (5-10d) and long-term (13-38d) SMF exposure on selective attention and motor coordination of rats, as well as associated alterations in expression level of neuroplasticity-related structural proteins and cryptochrome (CRY1) protein in the cortex, striatum and ventral midbrain. The results showed that 6d SMF exposure significantly enhanced selective attention without affecting locomotor activity in open field.

The prescriber's guide to classic MAO inhibitors (phenelzine, tranylcypromine, isocarboxazid) for treatment-resistant depression.

This article is a clinical guide which discusses the "state-of-the-art" usage of the classic monoamine oxidase inhibitor (MAOI) antidepressants (phenelzine, tranylcypromine, and isocarboxazid) in modern psychiatric practice. The guide is for all clinicians, including those who may not be experienced MAOI prescribers. It discusses indications, drug-drug interactions, side-effect management, and the safety of various augmentation strategies.

Liposome-based targeting of dopamine to the brain: a novel approach for the treatment of Parkinson's disease.

Delivery of drugs into the brain is poor due to the blood brain barrier (BBB). This study describes the development of a novel liposome-based brain-targeting drug delivery system. The liposomes incorporate a diacylglycerol moiety coupled through a linker to a peptide of 5 amino acids selected from amyloid precursor protein (APP), which is recognized by specific transporter(s)/receptor(s) in the BBB.

Static Magnetic Field Exposure In Vivo Enhances the Generation of New Doublecortin-expressing Cells in the Sub-ventricular Zone and Neocortex of Adult Rats.

Static magnetic field (SMF) is gaining interest as a potential technique for modulating CNS neuronal activity. Previous studies have shown a pro-neurogenic effect of short periods of extremely low frequency pulsatile magnetic fields (PMF) in vivo and pro-survival effect of low intensity SMF in cultured neurons in vitro, but little is known about the in vivo effects of low to moderate intensity SMF on brain functions. We investigated the effect of continuously-applied SMF on subventricular zone (SVZ) neurogenesis and immature doublecortin (DCX)-expressing cells in the neocortex of young adult rats and in primary cultures of cortical neurons in vitro.

Inhibitors of MAO-B and COMT: their effects on brain dopamine levels and uses in Parkinson's disease.

MAO-B and COMT are both enzymes involved in dopamine breakdown and metabolism. Inhibitors of these enzymes are used in the treatment of Parkinson's disease. This review article describes the scientific background to the localization and function of the enzymes, the physiological changes resulting from their inhibition, and the basic and clinical pharmacology of the various inhibitors and their role in treatment of Parkinson's disease.

Sensor Array for Detection of Early Stage Parkinson's Disease before Medication.

Early diagnosis of Parkinson's disease (PD) is important because it affects the choice of therapy and is subject to a relatively high degree of error. In addition, early detection of PD can potentially enable the start of neuroprotective therapy before extensive loss of dopaminergic neurons of the substantia nigra occurs. However, until now, studies for early detection of PD using volatile biomarkers sampled only treated and medicated patients.

Altered Volatile Organic Compound Profile in Transgenic Rats Bearing A53T Mutation of Human α-Synuclein: Comparison with Dopaminergic and Serotonergic Denervation.

Early diagnosis of Parkinson's disease (PD) is of great importance due its progressive phenotype. Neuroprotective drugs could potentially slow down disease progression if used at early stages. Previously, we have reported an altered content of volatile organic compounds (VOCs) in the breath of rats following a 50% reduction in striatal dopamine (DA) content induced by 6-hydroxydopamine.

Diagnosis and Classification of 17 Diseases from 1404 Subjects via Pattern Analysis of Exhaled Molecules.

We report on an artificially intelligent nanoarray based on molecularly modified gold nanoparticles and a random network of single-walled carbon nanotubes for noninvasive diagnosis and classification of a number of diseases from exhaled breath. The performance of this artificially intelligent nanoarray was clinically assessed on breath samples collected from 1404 subjects having one of 17 different disease conditions included in the study or having no evidence of any disease (healthy controls). Blind experiments showed that 86% accuracy could be achieved with the artificially intelligent nanoarray, allowing both detection and discrimination between the different disease conditions examined.

Inhibitors of MAO-A and MAO-B in Psychiatry and Neurology.

Inhibitors of MAO-A and MAO-B are in clinical use for the treatment of psychiatric and neurological disorders respectively. Elucidation of the molecular structure of the active sites of the enzymes has enabled a precise determination of the way in which substrates and inhibitor molecules are metabolized, or inhibit metabolism of substrates, respectively. Despite the knowledge of the strong antidepressant efficacy of irreversible MAO inhibitors, their clinical use has been limited by their side effect of potentiation of the cardiovascular effects of dietary amines ("cheese effect").

Effects of fibroblast transplantation into the internal pallidum on levodopa-induced dyskinesias in parkinsonian non-human primates.

Recent studies have shown that fibroblast transplantation can modify the activity of basal ganglia networks in models of Parkinson's disease. To determine its effects on parkinsonian motor symptoms, we performed autologous dermal fibroblast transplantation into the internal pallidum (GPi) in two parkinsonian rhesus monkeys with stable levodopa-induced dyskinesias (LIDs). Levodopa responses were assessed every week after transplantation for three months.

Distinguishing idiopathic Parkinson's disease from other parkinsonian syndromes by breath test.

Introduction: Diagnosis of different parkinsonian syndromes is linked with high misdiagnosis rates and various confounding factors. This is particularly problematic in its early stages. With this in mind, the current pilot study aimed to distinguish between Idiopathic Parkinson's Disease (iPD), other Parkinsonian syndromes (non-iPD) and healthy subjects, by a breath test that analyzes the exhaled volatile organic compounds using a highly sensitive nanoarray.

Neuroprotective effect of weak static magnetic fields in primary neuronal cultures.

Low intensity static magnetic fields (SMFs) interact with various biological tissues including the CNS, thereby affecting key biological processes such as gene expression, cell proliferation and differentiation, as well as apoptosis. Previous studies describing the effect of SMFs on apoptotic cell death in several non-neuronal cell lines, emphasize the importance of such a potential modulation in the case of neurodegenerative disorders, where apoptosis constitutes a major route via which neurons degenerate and die. In this study, we examine the effect of SMFs on neuronal survival in primary cortical and hippocampal neurons that constitute a suitable experimental system for modeling the neurodegenerative state in vitro.

Analysis of volatile organic compounds in rats with dopaminergic lesion: Possible application for early detection of Parkinson's disease.

Parkinson's disease (PD) is characterized by dopaminergic (DA) neuron depletion. Early detection of PD may help in selecting the appropriate treatment. Biomarkers of PD have been suggested, however none of these is currently in clinical use.

Update on the pharmacology of selective inhibitors of MAO-A and MAO-B: focus on modulation of CNS monoamine neurotransmitter release.

Inhibitors of monoamine oxidase (MAO) were initially used in medicine following the discovery of their antidepressant action. Subsequently their ability to potentiate the effects of an indirectly-acting sympathomimetic amine such as tyramine was discovered, leading to their limitation in clinical use, except for cases of treatment-resistant depression. More recently, the understanding that: a) potentiation of indirectly-acting sympathomimetic amines is caused by inhibitors of MAO-A but not by inhibitors of MAO-B, and b) that reversible inhibitors of MAO-A cause minimal tyramine potentiation, has led to their re-introduction to clinical use for treatment of depression (reversible MAO-A inhibitors and new dose form MAO-B inhibitor) and treatment of Parkinson's disease (MAO-B inhibitors).

Copper pathology in vulnerable brain regions in Parkinson's disease.

Synchrotron-based x-ray fluorescence microscopy, immunofluorescence, and Western blotting were used to investigate changes in copper (Cu) and Cu-associated pathways in the vulnerable substantia nigra (SN) and locus coeruleus (LC) and in nondegenerating brain regions in cases of Parkinson's disease (PD) and appropriate healthy and disease controls. In PD and incidental Lewy body disease, levels of Cu and Cu transporter protein 1, were significantly reduced in surviving neurons in the SN and LC. Specific activity of the cuproprotein superoxide dismutase 1 was unchanged in the SN in PD but was enhanced in the parkinsonian anterior cingulate cortex, a region with α-synuclein pathology, normal Cu, and limited cell loss.

Increased L-DOPA-derived dopamine following selective MAO-A or -B inhibition in rat striatum depleted of dopaminergic and serotonergic innervation.

Background And Purpose: Selective MAO type B (MAO-B) inhibitors are effective in potentiation of the clinical effect of L-DOPA in Parkinson's disease, but dopamine (DA) is deaminated mainly by MAO type A (MAO-A) in rat brain. We sought to clarify the roles of MAO-A and MAO-B in deamination of DA formed from exogenous L-DOPA in rat striatum depleted of dopaminergic, or both dopaminergic and serotonergic innervations. We also studied the effect of organic cation transporter-3 (OCT-3) inhibition by decinium-22 on extracellular DA levels following L-DOPA.

Selective inhibition of monoamine oxidase A or B reduces striatal oxidative stress in rats with partial depletion of the nigro-striatal dopaminergic pathway.

Partial lesion (50%) of the nigro-striatal dopaminergic pathway induces compensatory increase in dopamine release from the remaining neurons and increased extracellular oxidative stress (OS(-ec)) in the striatum. The present study was designed to explore the role of monoamine oxidase types A and B (MAO-A, MAO-B) in producing this increased oxidative stress. Lesion of the dopaminergic pathways in the CNS was produced in rats by intra-cerebroventricular injection of 6-hydroxydopamine (6-OHDA; 250 μg) and striatal microdialysis was carried out 5 weeks later.

Detection of asymptomatic nigrostriatal dopaminergic lesion in rats by exhaled air analysis using carbon nanotube sensors.

The ante-mortem diagnosis of Parkinson's disease (PD) still relies on clinical symptoms. Biomarkers could in principle be used for the early detection of PD-related neuronal damage, but no validated, inexpensive, and simple biomarkers are available yet. Here we report on the breath-print of presymptomatic PD in rats, using a model with 50% lesion of dopaminergic neurons in substantia nigra.

Parkin promotes degradation of the mitochondrial pro-apoptotic ARTS protein.

Parkinson's disease (PD) is associated with excessive cell death causing selective loss of dopaminergic neurons. Dysfunction of the Ubiquitin Proteasome System (UPS) is associated with the pathophysiology of PD. Mutations in Parkin which impair its E3-ligase activity play a major role in the pathogenesis of inherited PD.

Cardiovascular baroreceptor activity and selective inhibition of monoamine oxidase.

Cardiovascular baroreceptor responsiveness of conscious rats treated with selective inhibitors of monoamine oxidase (MAO) types A and B was determined by measurement of blood pressure (BP) and heart rate (HR) responses to intravenous injection of phenylephrine and sodium nitroprusside. Treatment with selegiline (1 or 5 mg/kg p.o.

Selective inhibitors of monoamine oxidase type B and the "cheese effect".

Potentiation of the cardiovascular and other effects of dietary tyramine by monoamine oxidase (MAO) inhibitors (cheese effect) has been a major limitation to clinical use of these drugs. The discovery that MAO exists in two distinct isoforms, MAO-A and MAO-B, together with the development of selective inhibitors of each isoform, enabled the understanding that selective inhibition of MAO-A, or inhibition of both isoforms, will cause cheese effect, but selective inhibition of MAO-B can be elicited without dangerous pressor reaction. This development has permitted the introduction of selective MAO-B inhibitors to clinical medicine for treatment of Parkinson's disease.

Alterations in striatal oxidative stress level produced by pharmacological manipulation of dopamine as shown by a novel synthetic marker molecule.

Oxidative stress (OS) is thought to participate in neurodegenerative diseases such as Parkinson's disease, but the contribution of dopamine metabolism and auto-oxidation to OS in Parkinson's and other diseases is not clear. Oxidative stress in rat striatum was measured by microdialysis using a novel synthetic compound composed of tyrosine and linoleic acid (LT), and determination of the oxidation products LT-OOH and LT-epoxy by HPLC-MS. Since LT is non-diffusible through the microdialysis membrane, the oxidized products formed in microdialyzate reflect oxidation state in the extracellular compartment.

Modulation of excessive neuronal activity by fibroblasts: potential use in treatment of Parkinson's disease.

Purpose: A number of neurological disorders are marked by increased or aberrant frequency of neuronal discharge in specific parts of the brain. Administration of drugs such as antiepileptic compounds results in the depression of neuronal activity in the whole brain, with the potential for serious side-effects. In the search for additional therapies to reduce the unphysiological electrical activity of over-active brain foci, we have examined the effect of fibroblasts transplanted to areas responsible for motor dysfunction in hemi-parkinsonian rats, since bursting synchronous discharges in internal segment of globus pallidus (GPi) are thought to be partially responsible for the movement disorders of PD.

Pharmacology of Rasagiline, a New MAO-B Inhibitor Drug for the Treatment of Parkinson's Disease with Neuroprotective Potential.

Rasagiline (Azilect) is a highly selective and potent propargylamine inhibitor of monoamine oxidase (MAO) type B. Like other similar propargylamine inhibitors, rasagiline binds covalently to the N5 nitrogen of the flavin residue of MAO, resulting in irreversible inactivation of the enzyme. Therapeutic doses of the drug which inhibit brain MAO-B by 95% or more cause minimal inhibition of MAO-A, and do not potentiate the pressor or other pharmacological effects of tyramine.