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https://www.readbyqxmd.com/read/29779176/intranasal-delivery-of-pgdnf-dna-nanoparticles-provides-neuroprotection-in-the-rat-6-hydroxydopamine-model-of-parkinson-s-disease
#1
Amirah E-E Aly, Brendan T Harmon, Linas Padegimas, Ozge Sesenoglu-Laird, Mark J Cooper, Barbara L Waszczak
Glial cell line-derived neurotrophic factor (GDNF) gene therapy could offer a disease-modifying treatment for Parkinson's disease (PD). Here, we report that plasmid DNA nanoparticles (NPs) encoding human GDNF administered intranasally to rats induce transgene expression in the brain and protect dopamine neurons in a model of PD. To first test whether intranasal administration could transfect cells in the brain, rats were sacrificed 1 week after intranasal pGDNF NPs or the naked plasmid. GDNF ELISA revealed significant increases in GDNF expression throughout the brain for both treatments...
May 19, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29779156/adolescent-isolation-rearing-produces-a-prepulse-inhibition-deficit-correlated-with-expression-of-the-nmda-glun1-subunit-in-the-nucleus-accumbens
#2
Megan L Fitzgerald, Virginia M Pickel
Adolescence is a transition period during which social interaction is necessary for normal brain and behavior development. Severely abnormal social interactions during adolescence can increase the incidence of lifelong psychiatric disease. Decreased prepulse inhibition (PPI) is a quantifiable hallmark of some psychiatric illnesses in humans and can be elicited in rodents by isolation rearing throughout the adolescent transition period. PPI is a measure of sensorimotor gating in which the nucleus accumbens (Acb) is crucially involved...
May 19, 2018: Brain Structure & Function
https://www.readbyqxmd.com/read/29779103/dopamine-synthesis-as-a-mechanism-of-brain-plasticity-in-nigrostriatal-system-pathology
#3
A A Kolacheva, M V Ugrumov
Using an experimental Parkinson's disease model (symptoms develop in mice after the injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine), we studied the characteristics of the synthesis of dopamine as a possible compensatory mechanism aimed at maintaining the dopamine level in the dopaminergic neurons that survived in this pathology. We found no correlation between the content and activity of tyrosine hydroxylase in the nigrostriatal system. The enzyme activity and the dopamine content showed unidirectional changes in the substantia nigra, but not in the striatum, which is apparently due to triggering other compensatory mechanisms...
March 2018: Doklady. Biochemistry and Biophysics
https://www.readbyqxmd.com/read/29778899/dopamine-loss-alters-the-hippocampus-nucleus-accumbens-synaptic-transmission-in-the-tg2576-mouse-model-of-alzheimer-s-disease
#4
Alberto Cordella, Paraskevi Krashia, Annalisa Nobili, Annabella Pignataro, Livia La Barbera, Maria Teresa Viscomi, Alessandro Valzania, Flavio Keller, Martine Ammassari-Teule, Nicola Biagio Mercuri, Nicola Berretta, Marcello D'Amelio
The functional loop involving the ventral tegmental area (VTA), dorsal hippocampus and nucleus accumbens (NAc) plays a pivotal role in the formation of spatial memory and persistent memory traces. In particular, the dopaminergic innervation from the VTA to the hippocampus is critical for hippocampal-related memory function and alterations in the midbrain dopaminergic system are frequently reported in Alzheimer's disease (AD), contributing to age-related decline in memory and non-cognitive functions. However, much less is known about the hippocampus-NAc connectivity in AD...
May 17, 2018: Neurobiology of Disease
https://www.readbyqxmd.com/read/29778792/valproic-acid-attenuates-manganese-induced-reduction-in-expression-of-glt-1-and-glast-with-concomitant-changes-in-murine-dopaminergic-neurotoxicity
#5
James Johnson, Edward Pajarillo, Pratap Karki, Judong Kim, Deok-Soo Son, Michael Aschner, Eunsook Lee
Exposure to elevated levels of manganese (Mn) causes manganism, a neurological disorder with similar characteristics to those of Parkinson's disease (PD). Valproic acid (VPA), an antiepileptic, is known to inhibit histone deacetylases and exert neuroprotective effects in many experimental models of neurological disorders. In the present study, we investigated if VPA attenuated Mn-induced dopaminergic neurotoxicity and the possible mechanisms involved in VPA's neuroprotection, focusing on modulation of astrocytic glutamate transporters (glutamate aspartate transporter, GLAST and glutamate transporter 1, GLT-1) and histone acetylation in H4 astrocyte culture and mouse models...
May 17, 2018: Neurotoxicology
https://www.readbyqxmd.com/read/29778625/the-mediating-role-of-phosphodiesterase-type-4-in-the-dopaminergic-modulation-of-motor-impulsivity
#6
P R A Heckman, A Blokland, N P Van Goethem, B T J Van Hagen, J Prickaerts
The current study investigated the mediating role of phosphodiesterase type 4 (PDE4) regulated cAMP in the dopaminergic modulation of premature responding (action restraint) in rats. Response inhibition, which includes action restraint, finds its neurobiological origin in cortico-striatal-thalamic circuitry and can be modulated by dopamine. Intracellularly, the effect of dopamine is largely mediated through the cAMP/PKA signaling cascade. Areas in the prefrontal cortex are very sensitive to their neurochemical environment, including catecholamine levels...
May 17, 2018: Behavioural Brain Research
https://www.readbyqxmd.com/read/29778509/longitudinal-observations-using-simultaneous-fmri-multiple-channel-electrophysiology-recording-and-chemical-microiontophoresis-in-the-rat-brain
#7
Saul Jaime, Jose E Cavazos, Yihong Yang, Hanbing Lu
BACKGROUND: fMRI blood oxygenation level-dependent (BOLD) signal has been widely used as a surrogate for neural activity. However, interpreting differences in BOLD fMRI based on underlying neuronal activity remains a challenge. Concurrent rsMRI data collection and electrophysiological recording in combination with microiontophoretically injected modulatory chemicals allows for improved understanding of the relationship between resting state BOLD and neuronal activity. NEW METHODS: Simultaneous fMRI, multi-channel intracortical electrophysiology and focal pharmacological manipulation data to be acquired longitudinally in rats for up to 2 months...
May 17, 2018: Journal of Neuroscience Methods
https://www.readbyqxmd.com/read/29776864/putaminal-dopamine-depletion-in-de-novo-parkinson-s-disease-predicts-future-development-of-wearing-off
#8
Su Jin Chung, Yoonju Lee, Jungsu S Oh, Jae Seung Kim, Phil Hyu Lee, Young H Sohn
INTRODUCTION: The present study aimed to investigate whether the level of presynaptic dopamine neuronal loss predicts future development of wearing-off in de novo Parkinson's disease. METHODS: This retrospective cohort study included a total of 342 non-demented patients with de novo Parkinson's disease who underwent dopamine transporter positron emission tomography scans at their initial evaluation and received dopaminergic medications for 24 months or longer. Onset of wearing-off was determined based on patients' medical records at their outpatient clinic visits every 3-6 months...
May 10, 2018: Parkinsonism & related Disorders
https://www.readbyqxmd.com/read/29776015/delta-9-tetrahydrocannabinol-potentiates-fear-memory-salience-through-functional-modulation-of-mesolimbic-dopaminergic-activity-states
#9
Aurelie Fitoussi, Jordan Zunder, Huibing Tan, Steven R Laviolette
Chronic or acute exposure to delta-9-tetrahydrocannabinol (THC), the main psychoactive compound in cannabis, has been associated with numerous neuropsychiatric side-effects, including dysregulation of emotional processing and associative memory formation. Clinical and pre-clinical evidence suggests that the effects of THC are due to the ability to modulate mesolimbic dopamine (DA) activity states in the nucleus accumbens (NAc) and ventral tegmental area (VTA). Nevertheless, the mechanisms by which THC modulates mesolimbic DA function and emotional processing are not well understood...
May 18, 2018: European Journal of Neuroscience
https://www.readbyqxmd.com/read/29775777/antidepressant-potential-of-novel-flavonoids-derivatives-from-sweet-violet-viola-odorata-l-pharmacological-biochemical-and-computational-evidences-for-possible-involvement-of-serotonergic-mechanism
#10
Nasiara Karim, Imran Khan, Abeer Abdelhalim, Ajmal Khan, Sobia Ahsan Halim
Plant-derived natural constituents are of great interest in modern drug discovery due to their natural diversity. Viola odorata L has been traditionally used for the treatment of neuropsychiatric disorders. The present study was undertaken to isolate phytoconstituents including three flavonoids 5,7-Dihydroxy-3,6-dimethoxyflavone[1] 5,7,4'-trihydroxy-3',5'dimethoxyflavone [2] and 5,7,4'-trihydroxy-3'-methoxyflavone [3] from the whole plant of Viola odorata L and to investigate the antidepressant-like effects of these compounds and their possible mechanism of action using antagonists of the serotonergic, dopaminergic and adrenergic system...
May 15, 2018: Fitoterapia
https://www.readbyqxmd.com/read/29775679/identification-and-validation-of-midbrain-kcnq4-regulation-of-heavy-alcohol-consumption-in-rodents
#11
Natalie S McGuier, Jennifer A Rinker, Reginald Cannady, Diana B Fulmer, Sara R Jones, Michaela Hoffman, Patrick J Mulholland
Currently available pharmacotherapies for treating alcohol use disorder (AUD) suffer from deleterious side effects and are not efficacious in diverse populations. Clinical and preclinical studies provide evidence that the Kcnq family of genes that encode KV 7 channels influence alcohol intake and dependence. KV 7 channels are a class of slowly activating voltage-dependent K+ channels that regulate neuronal excitability. Studies indicate that the KV 7 channel positive modulator retigabine can decrease dopaminergic neuron firing, alter dopamine (DA) release, and reduce alcohol intake in heavy drinking rodents...
May 15, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29775630/the-basolateral-amygdala-dopaminergic-system-contributes-to-the-improving-effect-of-nicotine-on-stress-induced-memory-impairment-in-rats
#12
Elnaz Keshavarzian, Zahra Ghasemzadeh, Ameneh Rezayof
Stress seems to be an important risk factor in the beginning and continuing stages of cigarette tobacco smoking in humans. Considering that both of nicotine administration and stress exposure affect cognitive functions including memory formation, the aim of the present study was 1) to evaluate the effect of subcutaneous (s.c.) administration of nicotine on memory formation under stress and 2) to assess the possible role of the basolateral amygdala (BLA) dopamine D1 and D2 receptors in the effect of nicotine on stress-induced memory retrieval impairment...
May 15, 2018: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/29774058/the-role-of-dopaminergic-immune-cell-signalling-in-poststroke-inflammation
#13
REVIEW
Daniela Talhada, Monika Rabenstein, Karsten Ruscher
Upon ischaemic stroke, brain-resident and peripheral immune cells accumulate in the central nervous system (CNS). Interestingly, these cells express pattern specific to neurotransmitter receptors and, therefore, seem to be susceptible to neurotransmitter stimulation, potentially modulating their properties and functions. One of the principal neurotransmitters in the CNS, dopamine, is involved in the regulation of processes of brain development, motor control and higher brain functions. It is constantly released in the brain and there is experimental and clinical evidence that dopaminergic signalling is involved in recovery of lost neurological function after stroke...
2018: Therapeutic Advances in Neurological Disorders
https://www.readbyqxmd.com/read/29774002/on-the-drive-specificity-of-freudian-drives-for-the-generation-of-seeking-activities-the-importance-of-the-underestimated-imperative-motor-factor
#14
Michael Kirsch, Wolfgang Mertens
Doubters of Freud's theory of drives frequently mentioned that his approach is outdated and therefore cannot be useful for solving current problems in patients with mental disorders. At present, many scientists believe that affects rather than drives are of utmost importance for the emotional life and the theoretical framework of affective neuroscience, developed by Panksepp, strongly underpinned this view. Panksepp evaluated seven so-called command systems and the SEEKING system is therein of central importance...
2018: Frontiers in Psychology
https://www.readbyqxmd.com/read/29773910/the-l-type-calcium-channel-blocker-isradipine-attenuates-cue-induced-cocaine-seeking-by-enhancing-dopaminergic-activity-in-the-ventral-tegmental-area-to-nucleus-accumbens-pathway
#15
Nii A Addy, Eric J Nunes, Shannon M Hughley, Keri M Small, Sarah J Baracz, Joshua L Haight, Anjali M Rajadhyaksha
Previous preclinical and clinical investigations have focused on the L-type calcium channel (LTCC) as a potential therapeutic target for substance abuse. While some clinical studies have examined the ability of LTCC blockers to alter cocaine's subjective effects, very few LTCC studies have examined cocaine relapse. Here, we examined whether ventral tegmental area (VTA)-specific or systemic administration of the LTCC inhibitor, isradipine, altered cocaine-seeking behavior in a rat model. Male Sprague-Dawley rats first received 10 days of cocaine self-administration training (2 h sessions), where active lever depression resulted in delivery of a ∼0...
May 3, 2018: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29773830/circadian-and-homeostatic-modulation-of-multi-unit-activity-in-midbrain-dopaminergic-structures
#16
Karim Fifel, Johanna H Meijer, Tom Deboer
Although the link between sleep disturbances and dopamine (DA)-related neurological and neuropsychiatric disorders is well established, the impact of sleep alterations on neuronal activity of midbrain DA-ergic structures is currently unknown. Here, using wildtype C57Bl mice, we investigated the circadian- and sleep-related modulation of electrical neuronal activity in midbrain ventral-tegmental-area (VTA) and substantia nigra (SN). We found no significant circadian modulation of activity in SN while VTA displayed a low amplitude but significant circadian modulation with increased firing rates during the active phase...
May 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29772521/myricetin-attenuates-neurodegeneration-and-cognitive-impairment-in-parkinsonism
#17
Vijayraja Dhanraj, Jeyaprakash Karuppaiah, Rengasamy Balakrishnan, Namasivayam Elangovan
Parkinson's disease (PD) is a progressive neurodegenerative disease due to dopaminergic neuron degeneration. It mostly affects the aged population, leads to memory decline and loss of motor coordination. The present study investigates the neuroprotective role of myricetin a flavonol isolated from the brown seaweed Turbinaria ornata in rotenone induced Drosophila model of PD. Rotenone administration led to dopaminergic neuronal degeneration, dopamine depletion, impaired muscular coordination, gait disturbances, memory decline oxidative stress and apoptosis...
June 1, 2018: Frontiers in Bioscience (Elite Edition)
https://www.readbyqxmd.com/read/29771174/signaling-and-induction-of-chaperone-mediated-autophagy-by-the-endoplasmic-reticulum-under-stress-conditions
#18
Wenming Li, Qian Yang, Zixu Mao
Chaperone-mediated autophagy (CMA), a form of selective autophagy, maintains cellular proteostasis in response to diverse stress conditions. Whether and how endoplasmic reticulum (ER) stress triggers CMA remains elusive. In our recent study, we demonstrate that various types of ER stress activate the CMA pathway via an EIF2AK3/PERK-MAP2K4/MKK4-MAPK14/p38-dependent manner. We term this process ERICA for ER stress-induced chaperone-mediated autophagy. This pathway is activated in response to stress associated with Parkinson disease and is required for the viability of the SNc dopaminergic neurons in an animal model of Parkinson disease...
May 17, 2018: Autophagy
https://www.readbyqxmd.com/read/29769744/nadph-ameliorates-mptp-induced-dopaminergic-neurodegeneration-through-inhibiting-p38mapk-activation
#19
Jing-Si Zhou, Zhou Zhu, Feng Wu, Ying Zhou, Rui Sheng, Jun-Chao Wu, Zheng-Hong Qin
Parkinson's disease (PD) is the second most common neurodegenerative disorder characterized by the selective loss of dopaminergic neurons in substantia nigra pars compacta (SNpc). Although the pathogenic mechanism underlying PD remains largely unknown, decreased nigral glutathione (GSH) in postmortem brains of PD patients supports the presence of oxidative stress in PD. We found that Nicotinamide adenine dinucleotide phosphate (NADPH), which is important for maintaining the level of GSH, protected dopaminergic (DA) neurons from neurotoxicity of MPTP/MPP+ ...
May 16, 2018: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/29769545/short-term-temporal-memory-in-idiopathic-and-parkin-associated-parkinson-s-disease
#20
Bertrand Degos, Ilhame Ameqrane, Sophie Rivaud-Péchoux, Pierre Pouget, Marcus Missal
In a rapidly changing environment, we often know when to do something before we have to do it. This preparation in the temporal domain is based on a 'perception' of elapsed time and short-term memory of previous stimulation in a similar context. These functions could be perturbed in Parkinson's disease. Therefore, we investigated their role in eye movement preparation in sporadic Parkinson's disease and in a very infrequent variant affecting the Parkin gene. We used a simple oculomotor task where subjects had to orient to a visual target and movement latency was measured...
May 16, 2018: Scientific Reports
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