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.

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.

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.

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.

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.

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.

Specific oxidative stress profile associated with partial striatal dopaminergic depletion by 6-hydroxydopamine as assessed by a novel multifunctional marker molecule.

Real time oxidative stress in the extracellular compartment of rat striatum was characterized by microdialysis with synthetic non-dialyzable marker molecules composed of linoleic acid, tyrosine and guanosine (N-linoleoyl tyrosine (LT) and N-linoleoyl tyrosine 2'-deoxyguanosyl ester (LTG)). Partial dopaminergic deafferentation was induced by injection of 6-hydroxydopamine (250 microg) to the left lateral ventricle, which depleted ipsilateral striatal dopamine by 46% and dopaminergic cells in left substantia nigra by 44%, 5 weeks after administration. Resting microdialysate dopamine levels in dopamine-depleted striatum were not different from sham-operated rats, although the ratio of oxidized metabolites of dopamine to free dopamine was significantly increased.

The reward system and maternal behavior in an animal model of depression: a microdialysis study.

Rationale And Objectives: Flinders sensitive line (FSL) rats, an animal model of depression, display a different pattern of maternal behavior compared to Sprague-Dawley (SD) controls. In this study, we examined the rewarding value of mother-infant interaction for FSL dams.

Materials And Methods: In the main study, we measured monoamine levels in the nucleus accumbens (NAc) of early postpartum FSL and SD dams during an interaction with pups, using the microdialysis technique.

A possible new role for fish retinal serotonin-N-acetyltransferase-1 (AANAT1): Dopamine metabolism.

Serotonin-N-acetyltransferase (arylalkylamine-N-acetyltransferase, AANAT) is the key enzyme in the generation of melatonin rhythms in the pineal gland and retinal photoreceptors. Rhythmic AANAT activity drives rhythmic melatonin production in these tissues. Two AANATs, AANAT1 and AANAT2, are present in teleost fish species.

Neurochemical evidence for agmatine modulation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxicity.

Agmatine treatment is known to exert neuroprotective effects in several models of neurotoxic and ischemic brain and spinal cord injuries. Here we sought to find out whether agmatine treatment would also prove to be neuroprotective in the mouse 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of Parkinson's disease. Concomitant daily treatment (intraperitoneal injections) with agmatine (100 mg/kg for 5 days) and MPTP (40 mg/kg for 2 days) exacerbated MPTP-related toxicity as evidenced by a larger reduction in dopamine uptake into striatal synaptosomes (42.

Regulation of the proapoptotic ARTS protein by ubiquitin-mediated degradation.

ARTS is a mitochondrial protein that promotes apoptosis induced by a variety of proapoptotic stimulators. ARTS induces apoptosis, at least in part, through binding to and antagonizing IAPs (inhibitors of apoptosis proteins). As a result of ARTS binding to IAPs, caspase inhibition is removed and apoptosis can be executed.

Characterization of the neuroprotective activity of rasagiline in cerebellar granule cells.

Rasagiline (N-propargyl-1-R-aminoindan) is a new selective inhibitor of MAO-B which is in development for the treatment of Parkinson's disease. The aim of the present study was to evaluate the neuroprotective properties of rasagiline and characterize the mechanism by which it exerts its neuroprotective effect in cerebellar granule cells. Cerebellar granule cells were prepared from 7 to 8 days postnatal Sprague-Dawley rats and maintained in high K(+) (25 mM) medium.

Rasagiline enhances L-DOPA-induced contralateral turning in the unilateral 6-hydroxydopamine-lesioned guinea-pig.

The modification of L-3,4-dihydrooxyphenylalanine- (L-DOPA-) induced turning response by the new selective monoamine oxidase type B (MAO-B) inhibitor rasagiline was studied in guinea-pigs bearing a unilateral 6-hydroxydopamine-induced lesion in the substantia nigra. In an initial experiment, it was established that contralateral turning is induced in lesioned guinea-pigs in response to apomorphine (18 mg/kg i.p.