Effect of antibodies to glutamate on age-related memory changes in C57Bl/6 mice

Chronic intranasal administration of antibodies to glutamate to aging C57Bl/6 mice improved passive avoidance conditioning, had no effect on horizontal and vertical locomotor activity, but slowed locomotion in the open-field test. Administration of antibodies to glutamate increased the content of dopamine and its metabolites in mouse hippocampus, but had no effect on the metabolism of neurotransmitter amino acids. In the frontal cortex, antibodies to glutamate did not affect neurotransmitter metabolism, but increased the level of both excitatory and inhibitory amino acids without changing their ratio

Delayed behavioral and neurochemical effects of anti-glutamate antibodies in aging C57BL/6 mice

We analyzed delayed effect of intranasal administration of anti-glutamate antibodies on mnestic function and tissue concentrations of neurotransmitters in the hippocampus and prefrontal cortex in aging C57BL/6 mice. It was found that after 14-day administration of anti-glutamate antibodies, improvement of the passive avoidance conditioning persisted for 7 days after the treatment was discontinued. In 7 days after discontinuation of treatment, increased content of dopamine and its metabolites as well as aspartic acid and taurine was observed in the hippocampus of mice treated with anti-glutamate antibodies. In the prefrontal cortex, administration of anti-glutamate antibodies had no effect on the levels of neurotransmitters, but increased the concentration of glutamate

Влияние фенибута и атомоксетина на биосинтез и метаболизм дофамина и серотонина в мозге мышей C57BL/6

The effect of intraperitoneal administration of the nootropic drug phenibut (70 mg/kg) and atomoxetine hydrochloride (3 mg/kg) on the neurochemical parameters of dopaminergic and serotonergic systems in the brain structures of C57BL/6 mice was studied by HPLC/ED. It was found that under in vivo blockade of L-aromatic amino acid decarboxylase (DAAA), both drugs in the selected doses did not affect directly on biosynthesis processes of both dopamine and serotonin in the prefrontal cortex and striatum of rodents. The observed effects of phenybut and atomoxetine hydrochloride, in comparison with the used D2 receptor ligands quinpirole (0.1 mg/kg) and sulpiride (25 mg/kg), suggest the absence of direct participation of dopamine autoreceptors regulating the functional activity of dopaminergic synapses.Методом ВЭЖХ/ЭД изучено влияние внутрибрюшинного введения ноотропного средства фенибута (70 мг/кг) и атомоксетина гидрохлорида (3 мг/кг) на нейрохимические показатели дофамин- и серотонинергических систем в структурах мозга мышей C57BL/6. Установлено, что в условиях in vivo блокады декарбоксилазы L-ароматических аминокислот (ДААК) оба препарата в выбранных дозах не оказывали прямого действия на процессы биосинтеза как дофамина, так и серотонина, в префронтальной коре и стриатуме грызунов. Обнаруженные эффекты фенибута и атомоксетина гидрохлорида, в сравнении с использованными  лигандами D2-рецепторов квинпиролом (0,1 мг/кг) и сульпиридом (25 мг/кг), позволяют предположить отсутствие прямого участия в них дофаминовых ауторецепторов, регулирующих функциональную активность дофаминергических синапсов

Влияние пирацетама и фенотропила на метаболизм дофамина и серотонина в мозге субпопуляций мышей CD-1, различающихся по устойчивости внимания

The effect of subchronic administration of the nootropics Phenotropil (100 mg/kg/day) on the behavior of CD-1 outbreed mice in the "closed enriched cross maze" test (CECM) was studied. Predominantly, the mouse population was divided into subpopulations according to their values of individual attention index for novel objects in the maze compartments – highly attentive (ED-high) and low attentive (ED-low). It was found that Phenotropil increased the attention index in ED-low, but disimproved it in the ED-high subpopulation, and also changed parameteres of anxiety and locomotor activity; this distinguished it from the more selective effect of Piracetam (200 mg/kg/day). The higher selectivity of Piracetam was also shown in relation to dopamine metabolism processes in the prefrontal cortex: the drug normalized the metabolic turnover of intracellular (DOPAC/DA) as well as extracellular (HVA/DA) dopamine, while Phenotropil influenced on the former only. Thus, positive effect of Piracetam on the attention level in ED-low mice corresponds to the normalization of both indicators of dopamine metabolism in the prefrontal cortex, while Phenotropil showed non-selectivity onto both behavioral and neurochemical parameters. Piracetam and Phenotropil failed to affect the cortical and striatal serotonin metabolism in both subpopulations.Изучено влияние субхронического введения ноотропного средства фенотропила (100 мг/кг/сутки) на поведение аутбредных мышей CD-1 в тесте «закрытый обогащённый крестообразный лабиринт». Предварительно популяция мышей была разделена на субпопуляции по величине индекса внимания особей к незнакомым объектам в отсеках лабиринта – высоковнимательных (ED-high) и низковнимательных (ED-low). Установлено, что фенотропил повышал индекс внимания у ED-low, однако ухудшал его в субпопуляции ED-high, а также изменял показатели тревожности и двигательной активности, что отличало его от более селективного эффекта пирацетама (200 мг/кг/сутки). Большая избирательность пирацетама отражалась и в отношении метаболизма дофамина в ткани префронтальной коры мозга: препарат нормализовал метаболический оборот как внутриклеточного (ДОФУК/ДА), так и внеклеточного (ГВК/ДА) дофамина, тогда как фенотропил корригировал лишь первый. Таким образом, положительное влияние пирацетама на индекс внимания у мышей ED-low соответствует нормализации обоих показателей метаболизма дофамина в префронтальной коре, а фенотропил проявлял неизбирательность как в отношении поведенческих, так и нейрохимических параметров. Оба препарата практически не затрагивали метаболизм серотонина как в коре, так и в стриатумах мышей обеих субпопуляций

S100A9 protein aggregates boost hippocampal glutamate modifying monoaminergic neurochemistry: A glutamate antibody sensitive outcome on Alzheimer-like memory decline

Alzheimer’s disease (AD) involves dementia conceivably arising from integrated inflammatory processes, amyloidogenesis, and neuronal apoptosis. Glutamate can also cause neuronal death via excitotoxicity, and this is similarly implicated in some neurological diseases. The aim was to examine treatment with in vitro generated proinflammatory protein S100A9 aggregate species alone or with glutamate antibodies (Glu-Abs) on Morris water maze (MWM) spatial learning and memory performance in 12 month old mice. Amino acid and monoamine cerebral neurotransmitter metabolic changes were concurrently monitored. Initially, S100A9 fibrils were morphologically verified by atomic force microscopy and Thioflavin T assay. They were then administered intranasally alone or with Glu-Abs for 14 days followed by a 5 day MWM protocol before hippocampal and prefrontal cortical neurochemical analysis. S100A9 aggregates evoked spatial amnesia which correlated with disrupted glutamate and dopaminergic neurochemistry. Hippocampal glutamate release, elevation of DOPAC and HVA, as well as DOPAC/DA and HVA/DA ratios were subsequently reduced by Glu-Abs which simultaneously prevented the spatial memory deficit. The present outcomes emphasized the pathogenic nature of S100A9 fibrillar aggregates in causing spatial memory amnesia associated with enhanced hippocampal glutamate release and DA-ergic disruption in the aging brain. This finding might be exploited during dementia management through a neuroprotective strategy

The Period Changes of the Cepheid RT Aurigae

Observations of the light curve for the 3.7-day Cepheid RT Aur both before and since 1980 indicate that the variable is undergoing an overall period increase, amounting to +0.082 +-0.012 s/yr, rather than a period decrease, as implied by all observations prior to 1980. Superposed on the star's O-C variations is a sinusoidal trend that cannot be attributed to random fluctuations in pulsation period. Rather, it appears to arise from light travel time effects in a binary system. The derived orbital period for the system is P = 26,429 +-89 days (72.36 +-0.24 years). The inferred orbital parameters from the O-C residuals differ from those indicated by existing radial velocity data. The latter imply the most reasonable results, namely a1 sin i = 9.09 (+-1.81) x 10^8 km and a minimum secondary mass of M2 = 1.15 +-0.25 Msun. Continued monitoring of the brightness and radial velocity changes in the Cepheid are necessary to confirm the long-term trend and to provide data for a proper spectroscopic solution to the orbit.Comment: Accepted for publication in PASP (November 2007

The misfolded pro-inflammatory protein S100A9 disrupts memory via neurochemical remodelling instigating an Alzheimer's disease-like cognitive deficit

Memory deficits may develop from a variety of neuropathologies including Alzheimer’s disease dementia. During neurodegenerative conditions there are contributory factors such as neuroinflammation and amyloidogenesis involved in memory impairment. In the present study, dual properties of S100A9 protein as a pro-inflammatory and amyloidogenic agent were explored in the passive avoidance memory task along with neurochemical assays in the prefrontal cortex and hippocampus of aged mice. S100A9 oligomers and fibrils were generated in vitro and verified by AFM, Thioflavin T and A11 antibody binding. Native S100A9 as well as S100A9 oligomers and fibrils or their combination were administered intranasally over 14 days followed by behavioral and neurochemical analysis. Both oligomers and fibrils evoked amnestic activity which correlated with disrupted prefrontal cortical and hippocampal dopaminergic neurochemistry. The oligomer-fibril combination produced similar but weaker neurochemistry to the fibrils administered alone but without passive avoidance amnesia. Native S100A9 did not modify memory task performance even though it generated a general and consistent decrease in monoamine levels (DA, 5-HT and NA) and increased metabolic marker ratios of DA and 5-HT turnover (DOPAC/DA, HVA/DA and 5-HIAA) in the prefrontal cortex. These results provide insight into a novel pathogenetic mechanism underlying amnesia in a fear-aggravated memory task based on amyloidogenesis of a pro-inflammatory factor leading to disrupted brain neurochemistry in the aged brain. The data further suggests that amyloid species of S100A9 create deleterious effects principally on the dopaminergic system and this novel finding might be potentially exploited during dementia management through a neuroprotective strategy

Intranasal administration of alpha-synuclein aggregates: a Parkinson's disease model with behavioral and neurochemical correlates

Parkinson's disease (PD) is a neurodegenerative disorder in which both alpha-synuclein (α-syn) and dopamine (DA) have a critical role. Our previous studies instigated a novel PD model based on nasal inoculation with α-syn aggregates which expressed parkinsonian-like behavioral and immunological features. The current study in mice substantiated the robustness of the amyloid nasal vector model by examining behavioral consequences with respect to DA-ergic neurochemical corollaries. In vitro generated α-syn oligomers and fibrils were characterized using atomic force microscopy and the thioflavin T binding assay. These toxic oligomers or fibrils administered alone (0.48 mg/kg) or their 50:50 combination (total dose of 0.48 mg/kg) were given intranasally for 14 days and “open-field” behavior was tested on days 0, 15 and 28 of the protocol. Behavioral deficits at the end of the 14-day dosing regime and on day 28 (i.e., 14 days after treatment completion) induced rigidity, hypokinesia and immobility. This was accompanied by elevated nigral but not striatal DA, DOPAC and HVA concentrations in response to dual administration of α-syn oligomers plus fibrils but not the oligomers by themselves. α-Syn fibrils intensified not only the hypokinesia and immobility 14 days post treatment, but also reduced vertical rearing and enhanced DA levels in the substantia nigra. Only nigral DA turnover (DOPAC/DA but not HVA/DA ratio) was augmented in response to fibril treatment but there were no changes in the striatum. Compilation of these novel behavioral and neurochemical findings substantiate the validity of the α-syn nasal vector model for investigating parkinsonian-like symptoms

РАДИАЦИОННО-ГИГИЕНИЧЕСКОЕ ОБОСНОВАНИЕ РАДИОНУКЛИДНОЙ ТЕРАПИИ В АМБУЛАТОРНОМ РЕЖИМЕ

The possibility of the use of the different therapeutic radiopharmaceuticals labeled with one of the 19 β-γ-emitting radionuclides or 6 α-β-γ-emitting radionuclides in the outpatient regime was identified in the estimateinvestigations. A criterion for admissibility of outpatient regime is effective dose of individuals from the population who occasionally or permanently contact the patients after the radiopharmaceutical introduction. Basing on the dose limits established by the Radiation Safety Standard-99/2009, maximal allowable activities of the mentioned radionuclides were calculated for various geometries and exposure scenarios. It is shown that only patients taking radionuclide therapy courses with 111In and 131I have to be hospitalized even in the case of the most conservative exposure conditions.В  расчетных  исследованиях  определена  возможность  использования  в  амбулаторном  режиме различных терапевтических радиофармпрепаратов (РФП), меченных одним из 19 β-γ-излучающих радионуклидов или из 6 α-β-γ-излучающих радионуклидов. Критерием допустимости амбулаторного режима является эффективная доза облучения отдельных лиц из населения, которые эпизодически или постоянно контактируют с больным после введения ему РФП. На основе пределов доз, установленных в НРБ-99/2009, рассчитаны максимально допустимые активности указанных радионуклидов для различных геометрий и сценариев облучения. Показано, что даже для наиболее консервативных условий облучения госпитализации подлежат больные, проходящие курсы радионуклидной терапии только с 111In и 131I