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https://www.readbyqxmd.com/read/29362376/a-mouse-model-of-autism-implicates-endosome-ph-in-the-regulation-of-presynaptic-calcium-entry
#1
Julie C Ullman, Jing Yang, Michael Sullivan, Jacob Bendor, Jonathan Levy, Ellen Pham, Katlin Silm, Helia Seifikar, Vikaas S Sohal, Roger A Nicoll, Robert H Edwards
Psychoactive compounds such as chloroquine and amphetamine act by dissipating the pH gradient across intracellular membranes, but the physiological mechanisms that normally regulate organelle pH remain poorly understood. Interestingly, recent human genetic studies have implicated the endosomal Na+/H+ exchanger NHE9 in both autism spectrum disorders (ASD) and attention deficit hyperactivity disorder (ADHD). Plasma membrane NHEs regulate cytosolic pH, but the role of intracellular isoforms has remained unclear...
January 23, 2018: Nature Communications
https://www.readbyqxmd.com/read/29315692/comprehensive-review-of-cardiovascular-toxicity-of-drugs-and-related-agents
#2
REVIEW
Přemysl Mladěnka, Lenka Applová, Jiří Patočka, Vera Marisa Costa, Fernando Remiao, Jana Pourová, Aleš Mladěnka, Jana Karlíčková, Luděk Jahodář, Marie Vopršalová, Kurt J Varner, Martin Štěrba
Cardiovascular diseases are a leading cause of morbidity and mortality in most developed countries of the world. Pharmaceuticals, illicit drugs, and toxins can significantly contribute to the overall cardiovascular burden and thus deserve attention. The present article is a systematic overview of drugs that may induce distinct cardiovascular toxicity. The compounds are classified into agents that have significant effects on the heart, blood vessels, or both. The mechanism(s) of toxic action are discussed and treatment modalities are briefly mentioned in relevant cases...
January 5, 2018: Medicinal Research Reviews
https://www.readbyqxmd.com/read/29154915/cocaine-and-amphetamine-regulated-transcript-peptide-and-calcium-binding-proteins-immunoreactivity-in-the-deep-layers-of-the-superior-colliculus-of-the-guinea-pig-implications-for-multisensory-and-visuomotor-processing
#3
Janusz Najdzion
The superior colliculus (SC) of mammals is a midbrain center, that can be subdivided into the superficial (SCs) and deep layers (SCd). In contrast to the visual SCs, the SCd are involved in multisensory and motor processing. This study investigated the pattern of distribution and colocalization of cocaine- and amphetamine-regulated transcript peptide (CART) and three calcium-binding proteins (CaBPs) i.e. calbindin (CB), calretinin (CR) and parvalbumin (PV) in the SCd of the guinea pig. CART labeling was seen almost exclusively in the neuropil and fibers, which differed in regard to morphology and location...
November 14, 2017: Journal of Chemical Neuroanatomy
https://www.readbyqxmd.com/read/29149481/neuroprotective-effects-of-melatonin-on-amphetamine-induced-dopaminergic-fiber-degeneration-in-the-hippocampus-of-postnatal-rats
#4
Tanawan Leeboonngam, Ratchadaporn Pramong, Kwankanit Sae-Ung, Piyarat Govitrapong, Pansiri Phansuwan-Pujito
Chronic amphetamine (AMPH) abuse leads to damage of the hippocampus, the brain area associated with learning and memory process. Previous results have shown that AMPH-induced dopamine neurotransmitter release, reactive oxygen species formation, and degenerative protein aggregation lead to neuronal death. Melatonin, a powerful antioxidant, plays a role as a neuroprotective agent. The objective of this study was to investigate whether the protective effect of melatonin on AMPH-induced hippocampal damage in the postnatal rat acts through the dopaminergic pathway...
November 17, 2017: Journal of Pineal Research
https://www.readbyqxmd.com/read/29104429/role-of-melatonin-in-reducing-amphetamine-induced-degeneration-in-substantia-nigra-of-rats-via-calpain-and-calpastatin-interaction
#5
Jirapa Chetsawang, Sujira Mukda, Rachneekorn Srimokra, Piyarat Govitrapong, Banthit Chetsawang
Excessive intracellular calcium levels induce calpain activation, thereby triggering the cell death cascade. Several lines of evidence have demonstrated the neuroprotective role of the overexpression of calpain inhibitor, calpastatin. In this study, amphetamine-induced degeneration in the substantia nigra of rats was determined by evaluating the decrease in the levels of tyrosine hydroxylase phosphorylation. Amphetamine significantly decreased calpastatin levels but increased calpain levels. An induction in calpain activity was demonstrated by an increase in the formation of calpain spectrin breakdown products...
2017: Journal of Experimental Neuroscience
https://www.readbyqxmd.com/read/28657744/discovery-of-n-substituted-2-phenylcyclopropyl-methylamines-as-functionally-selective-serotonin-2c-receptor-agonists-for-potential-use-as-antipsychotic-medications
#6
Guiping Zhang, Jianjun Cheng, John D McCorvy, Paul J Lorello, Barbara J Caldarone, Bryan L Roth, Alan P Kozikowski
A series of N-substituted (2-phenylcyclopropyl)methylamines were designed and synthesized, with the aim of finding serotonin 2C (5-HT2C)-selective agonists with a preference for Gq signaling. A number of these compounds exhibit 5-HT2C selectivity with a preference for Gq-mediated signaling compared with β-arrestin recruitment. Furthermore, the N-methyl compound (+)-15a, which displayed an EC50 of 23 nM in the calcium flux assay while showing no β-arrestin recruitment activity, is the most functionally selective 5-HT2C agonist reported to date...
July 27, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28596834/acute-cocaine-exposure-elicits-rises-in-calcium-in-arousal-related-laterodorsal-tegmental-neurons
#7
Mads Ødum Lambert, Theis Højland Ipsen, Kristi Anne Kohlmeier
Cocaine has strong reinforcing properties, which underlie its high addiction potential. Reinforcement of use of addictive drugs is associated with rises in dopamine (DA) in mesoaccumbal circuitry. Excitatory afferent input to mesoaccumbal circuitry sources from the laterodorsal tegmental nucleus (LDT). Chronic, systemic cocaine exposure has been shown to have cellular effects on LDT cells, but acute actions of local application have never been demonstrated. Using calcium imaging, we show that acute application of cocaine to mouse brain slices induces calcium spiking in cells of the LDT...
February 2017: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/28243192/the-sodium-channel-%C3%AE-4-auxiliary-subunit-selectively-controls-long-term-depression-in-core-nucleus-accumbens-medium-spiny-neurons
#8
Xincai Ji, Sucharita Saha, Guangping Gao, Amy W Lasek, Gregg E Homanics, Melissa Guildford, Andrew R Tapper, Gilles E Martin
Voltage-gated sodium channels are essential for generating the initial rapid depolarization of neuronal membrane potential during action potentials (APs) that enable cell-to-cell communication, the propagation of signals throughout the brain, and the induction of synaptic plasticity. Although all brain neurons express one or several variants coding for the core pore-forming sodium channel α subunit, the expression of the β (β1-4) auxiliary subunits varies greatly. Of particular interest is the β4 subunit, encoded by the Scn4b gene, that is highly expressed in dorsal and ventral (i...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28112453/food-restriction-induces-synaptic-incorporation-of-calcium-permeable-ampa-receptors-in-nucleus-accumbens
#9
Jiangyong Ouyang, Ioana Carcea, Jennifer K Schiavo, Kymry T Jones, Ariana Rabinowitsch, Rhonda Kolaric, Soledad Cabeza de Vaca, Robert C Froemke, Kenneth D Carr
Chronic food restriction potentiates behavioral and cellular responses to drugs of abuse and D-1 dopamine receptor agonists administered systemically or locally in the nucleus accumbens (NAc). However, the alterations in NAc synaptic transmission underlying these effects are incompletely understood. AMPA receptor trafficking is a major mechanism for regulating synaptic strength, and previous studies have shown that both sucrose and d-amphetamine rapidly alter the abundance of AMPA receptor subunits in the NAc postsynaptic density (PSD) in a manner that differs between food-restricted and ad libitum fed rats...
March 2017: European Journal of Neuroscience
https://www.readbyqxmd.com/read/27958713/inositol-phosphate-accumulation-in-vivo-provides-a-measure-of-muscarinic-m1-receptor-activation
#10
Michael Popiolek, David P Nguyen, Veronica Reinhart, Jeremy R Edgerton, John Harms, Susan M Lotarski, Stefanus J Steyn, Jennifer E Davoren, Sarah Grimwood
The rationale for using M1 selective muscarinic acetylcholine receptor activators for the treatment of cognitive impairment associated with psychiatric and neurodegenerative disease is well-established in the literature. Here, we investigate measurement of inositol phosphate accumulation, an end point immediately downstream of the M1 muscarinic acetylcholine receptor signaling cascade, as an in vivo biochemical readout for M1 muscarinic acetylcholine receptor activation. Five brain penetrant M1-subtype selective activators from three structurally distinct chemical series were pharmacologically profiled for functional activity in vitro using recombinant cell calcium mobilization and inositol phosphate assays, and a native tissue hippocampal slice electrophysiology assay, to show that all five compounds presented a positive allosteric modulator agonist profile, within a narrow range of potencies...
December 27, 2016: Biochemistry
https://www.readbyqxmd.com/read/27908658/cocaine-and-amphetamine-regulated-transcript-peptide-and-calcium-binding-proteins-immunoreactivity-in-the-superficial-layers-of-the-superior-colliculus-in-the-guinea-pig-implications-for-visual-sensory-processing
#11
Janusz Najdzion
The purpose of this study was to investigate the distribution and colocalization of cocaine- and amphetamine-regulated transcript peptide (CART) and three calcium-binding proteins (calbindin, calretinin and parvalbumin) in the superficial layers of the superior colliculus (SCs) in the guinea pig. The CART immunoreactivity was observed exclusively in the solitary fibers and neuropil, which formed various CART-ir tiers, that corresponded partially or entirely to anatomically defined layers of the SCs. The CART-ir structures exhibited a characteristic morphology with bundles of densely intermingled neuronal fibers and terminals...
January 2017: Journal of Chemical Neuroanatomy
https://www.readbyqxmd.com/read/27663745/exposure-to-amphetamines-leads-to-development-of-amphetamine%C3%A2-type-stimulants%C3%A2-associated-cardiomyopathy-atsac
#12
REVIEW
Mahsa Jafari Giv
With rapidly rising prevalence of exposure to Amphetamine Type Stimulants (ATS), novel insights into cardiotoxic effects of this substance are being presented in the literature and remarkably ATS Associated Cardiomyopathy (ATSAC) is emerging as a novel cardiovascular condition with its distinctive pathogenesis, risk factors, clinical features and prognosis. A comprehensive systematic review was performed to explore and analyze the current evidence on the association between ATS exposure and development of cardiomyopathy, biological mechanisms involved in pathogenesis of ATSAC, risk factors, clinical features and course of patients with ATSAC...
January 2017: Cardiovascular Toxicology
https://www.readbyqxmd.com/read/27623093/pkc%C3%AE-knockout-mice-are-protected-from-para-methoxymethamphetamine-induced-mitochondrial-stress-and-associated-neurotoxicity-in-the-striatum-of-mice
#13
Eun-Joo Shin, Duy-Khanh Dang, Hai-Quyen Tran, Yunsung Nam, Ji Hoon Jeong, Young Hun Lee, Kyung Tae Park, Yong Sup Lee, Choon-Gon Jang, Jau-Shyong Hong, Toshitaka Nabeshima, Hyoung-Chun Kim
Para-methoxymethamphetamine (PMMA) is a para-ring-substituted amphetamine derivative sold worldwide as an illegal psychotropic drug. Although PMMA use has been reported to lead to severe intoxication and even death, little is known about the mechanism(s) by which PMMA exerts its neurotoxic effects. Here we found that PMMA treatment resulted in phosphorylation of protein kinase Cδ (PKCδ) and subsequent mitochondrial translocation of cleaved PKCδ. PMMA-induced oxidative stress was more pronounced in mitochondria than in the cytosol...
September 10, 2016: Neurochemistry International
https://www.readbyqxmd.com/read/27578016/neurochemistry-of-the-anterior-thalamic-nuclei
#14
REVIEW
Witold Żakowski
This paper reviews the distribution of several bioactive substances and their possible physiological roles in the anterior thalamic nuclei of various species, with a special emphasis on the rat. The anterior thalamus is a part of extended hippocampal system and its significance for learning and memory processes is well known. Although our knowledge about a specific role of this brain structure has increased in recent years considerably, this is the first attempt to summarize neurochemical diversity of the anterior thalamus...
September 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/27260673/inhibition-by-ketamine-and-amphetamine-analogs-of-the-neurogenic-nitrergic-vasodilations-in-porcine-basilar-arteries
#15
Mei-Fang Chen, Su-Yu Lai, Po-Cheng Kung, Yo-Cheng Lin, Hui-I Yang, Po-Yi Chen, Ingrid Y Liu, Ahai Chang Lua, Tony Jer-Fu Lee
The abuse of ketamine and amphetamine analogs is associated with incidence of hypertension and strokes involving activation of sympathetic activities. Large cerebral arteries at the base of the brain from several species receive dense sympathetic innervation which upon activation causes parasympathetic-nitrergic vasodilation with increased regional blood flow via axo-axonal interaction mechanism, serving as a protective mechanism to meet O2 demand in an acutely stressful situation. The present study was designed to examine effects of ketamine and amphetamine analogs on axo-axonal interaction-mediated neurogenic nitrergic vasodilation in porcine basilar arteries using techniques of blood-vessel myography, patch clamp and two-electrode voltage clamp, and calcium imaging...
August 15, 2016: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/27149913/neurotoxicity-screening-of-illicit-drugs-using-novel-methods-for-analysis-of-microelectrode-array-mea-recordings
#16
L Hondebrink, A H A Verboven, W S Drega, S Schmeink, M W G D M de Groot, R G D M van Kleef, F M J Wijnolts, A de Groot, J Meulenbelt, R H S Westerink
Annual prevalence of the use of common illicit drugs and new psychoactive substances (NPS) is high, despite the often limited knowledge on the health risks of these substances. Recently, cortical cultures grown on multi-well microelectrode arrays (mwMEAs) have been used for neurotoxicity screening of chemicals, pharmaceuticals, and toxins with a high sensitivity and specificity. However, the use of mwMEAs to investigate the effects of illicit drugs on neuronal activity is largely unexplored. We therefore first characterised the cortical cultures using immunocytochemistry and show the presence of astrocytes, glutamatergic and GABAergic neurons...
July 2016: Neurotoxicology
https://www.readbyqxmd.com/read/26617160/cocaine-and-amphetamine-regulated-transcript-and-calcium-binding-proteins-immunoreactivity-in-the-subicular-complex-of-the-guinea-pig
#17
Barbara Wasilewska, Janusz Najdzion, Maciej Równiak, Krystyna Bogus-Nowakowska, Beata Hermanowicz, Małgorzata Kolenkiewicz, Witold Żakowski, Anna Robak
In this study we present the distribution and colocalization pattern of cocaine- and amphetamine-regulated transcript (CART) and three calcium-binding proteins: calbindin (CB), calretinin (CR) and parvalbumin (PV) in the subicular complex (SC) of the guinea pig. The subiculum (S) and presubiculum (PrS) showed higher CART-immunoreactivity (-IR) than the parasubiculum (PaS) as far as the perikarya and neuropil were concerned. CART- IR cells were mainly observed in the pyramidal layer and occasionally in the molecular layer of the S...
March 2016: Annals of Anatomy, Anatomischer Anzeiger: Official Organ of the Anatomische Gesellschaft
https://www.readbyqxmd.com/read/26300320/multiple-functions-of-neuronal-plasma-membrane-neurotransmitter-transporters
#18
REVIEW
Luca Raiteri, Maurizio Raiteri
Removal from receptors of neurotransmitters just released into synapses is one of the major steps in neurotransmission. Transporters situated on the plasma membrane of nerve endings and glial cells perform the process of neurotransmitter (re)uptake. Because the density of transporters in the membranes can fluctuate, transporters can determine the transmitter concentrations at receptors, thus modulating indirectly the excitability of neighboring neurons. Evidence is accumulating that neurotransmitter transporters can exhibit multiple functions...
November 2015: Progress in Neurobiology
https://www.readbyqxmd.com/read/26162812/amphetamine-activates-calcium-channels-through-dopamine-transporter-mediated-depolarization
#19
Krasnodara N Cameron, Ernesto Solis, Iwona Ruchala, Louis J De Felice, Jose M Eltit
Amphetamine (AMPH) and its more potent enantiomer S(+)AMPH are psychostimulants used therapeutically to treat attention deficit hyperactivity disorder and have significant abuse liability. AMPH is a dopamine transporter (DAT) substrate that inhibits dopamine (DA) uptake and is implicated in DA release. Furthermore, AMPH activates ionic currents through DAT that modify cell excitability presumably by modulating voltage-gated channel activity. Indeed, several studies suggest that monoamine transporter-induced depolarization opens voltage-gated Ca(2+) channels (CaV), which would constitute an additional AMPH mechanism of action...
November 2015: Cell Calcium
https://www.readbyqxmd.com/read/26157160/suppressed-bone-remodeling-in-black-bears-conserves-energy-and-bone-mass-during-hibernation
#20
Meghan McGee-Lawrence, Patricia Buckendahl, Caren Carpenter, Kim Henriksen, Michael Vaughan, Seth Donahue
Decreased physical activity in mammals increases bone turnover and uncouples bone formation from bone resorption, leading to hypercalcemia, hypercalcuria, bone loss and increased fracture risk. Black bears, however, are physically inactive for up to 6 months annually during hibernation without losing cortical or trabecular bone mass. Bears have been shown to preserve trabecular bone volume and architectural parameters and cortical bone strength, porosity and geometrical properties during hibernation. The mechanisms that prevent disuse osteoporosis in bears are unclear as previous studies using histological and serum markers of bone remodeling show conflicting results...
July 2015: Journal of Experimental Biology
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