RESUMEN
The activity in the open field, short- and long-term memory in the novel object recognition test, and gait features were evaluated in 6- and 12-month-old male C57BL/6 mice. The levels of norepinephrine, dopamine, serotonin, and their metabolites were determined in the cerebellum and frontal cortex. In the observed age range, a decrease in locomotion speed, impairment of gait initiation and stability, and long-term memory deficit were revealed. In the cerebral cortex, reduced levels of dopamine and its metabolites and accelerated metabolism of all neurotransmitters under study were found. In the cerebellum, the content of all studied monoamines was elevated, while dopamine metabolism was decelerated. Analysis of correlations between the neurochemical and behavioral parameters showed that the mechanisms of compensation of brain functions during the early aging may be associated with an increase in activity of the monoaminergic systems in the cerebellum.
Asunto(s)
Dopamina , Norepinefrina , Ratones , Animales , Masculino , Dopamina/metabolismo , Ratones Endogámicos C57BL , Norepinefrina/metabolismo , Cognición , Cerebelo/metabolismo , Lóbulo Frontal/metabolismo , Envejecimiento , Encéfalo/metabolismo , Monoaminas Biogénicas/metabolismoRESUMEN
The prognostic models assessing the risk of prehypertension in coming 1-2-year period for 30-60-year-old subjects were developed with the help of computer recognition technology using 6 recognition methods. These models are based on the content of molecular markers in blood serum and the risk factors for the development of prehypertension in men and women who had "optimal" BP for last 3 years and in patients with newly diagnosed prehypertension. The models were compared for their prediction power. The most effective model was obtained with gradient boosting method based on the content of molecular markers. It is characterized with a high predictive power (ROC AUC=0.76), specificity (96.4%), and overall accuracy (86.6%) accompanied with close relationship between prognosis and actual symptoms of prehypertension (p=0.001).
Asunto(s)
Prehipertensión/patología , Adulto , Biomarcadores/metabolismo , Presión Sanguínea/fisiología , Humanos , Persona de Mediana Edad , Prehipertensión/fisiopatología , PronósticoRESUMEN
The concentrations of the key factors of molecular pathogenesis of prehypertension (angiotensin II, HLDF24, S100b, endothelin, autoantibodies to these molecules, and VEGF) were analyzed in subjects with optimal BP (<120/80 mm Hg) and prehypertension (120-139/80-89 mm Hg). Comparative and correlation analysis of the levels of these molecules was performed. A statistically significant decrease in HLDF24 level in prehypertension in comparison optimal BP was observed. Specific features and interactions between the studied factors in optimal BP and in prehypertension were studied. The mechanisms underlying the observed associations between serum concentration of HLFF24 and the development of prehypertension were discussed.
Asunto(s)
Biomarcadores/sangre , Proteínas de Neoplasias/sangre , Fragmentos de Péptidos/sangre , Prehipertensión/sangre , Angiotensina II/sangre , Autoanticuerpos/sangre , Presión Sanguínea/fisiología , Endotelinas/sangre , Femenino , Humanos , Hipertensión/sangre , Masculino , Persona de Mediana Edad , Subunidad beta de la Proteína de Unión al Calcio S100/sangreRESUMEN
The neuroprotective and nootropic activities of the amide form (AF) of the HLDF-6 peptide (TGENHR-NH2) were studied in transgenic mice of the B6C3-Tg(APPswe,PSEN1de9)85Dbo (Tg+) line (the animal model of familial Alzheimer's disease (AD)). The study was performed in 4 mouse groups: group 1 (study group): Tg+ mice intranasally injected with the peptide at a dose of 250 µg/kg; group 2 (active control): Tg+ mice intranasally injected with normal saline; group 3 (control 1): Tg- mice; and group 4 (control 2): C57Bl/6 mice. The cognitive functions were evaluated using three tests: the novel object recognition test, the conditioned passive avoidance task, and the Morris water maze. The results testify to the fact that the pharmaceutical substance (PhS) based on the AF of HLDF-6 peptide at a dose of 250 µg/kg administered intranasally efficiently restores the disturbed cognitive functions in transgenic mice. These results are fully consistent with the data obtained in animal models of Alzheimer's disease induced by the injection of the beta-amyloid (ßA) fragment 25-35 into the giant-cell nucleus basalis of Meynert or by co-injection of the ßA fragment 25-35 and ibotenic acid into the hippocampus, and the model of ischemia stroke (chronic bilateral occlusion of carotids, 2VO). According to the overall results, PhS based on AF HLDF-6 was chosen as an object for further investigation; the dose of 250 µg/kg was used as an effective therapeutic dose. Intranasal administration was the route for delivery.
RESUMEN
The expression of Notch2, Numb, and Cas8 genes, whose protein products are involved in regulation of neurogenesis/neuroapoptosis processes, was studied in the relevant cerebral structures of male Wistar rats trained in a spatial habit. The formation of long-term spatial memory was found to be associated with the formation of a specific pattern of transcription activity of the studied genes in different brain structures. The maximum expression of Notch2 gene was found in the hippocampus and cerebellum, the maximum expression of Numb was detected in the prefrontal cortex and cerebellum, and the maximum expression of Cas8 was revealed in the prefrontal cortex of trained animals.
Asunto(s)
Caspasa 8/genética , Cerebelo/metabolismo , Hipocampo/metabolismo , Péptidos y Proteínas de Señalización Intracelular/genética , Memoria a Largo Plazo/fisiología , Corteza Prefrontal/metabolismo , Receptor Notch2/genética , Animales , Mapeo Encefálico , Caspasa 8/metabolismo , Cerebelo/anatomía & histología , Regulación de la Expresión Génica , Hipocampo/anatomía & histología , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Masculino , Aprendizaje por Laberinto/fisiología , Corteza Prefrontal/anatomía & histología , Ratas , Ratas Wistar , Receptor Notch2/metabolismo , Transducción de Señal , Natación/psicologíaRESUMEN
We studied concentrations of angiotensin II, HLDF24 peptide, endothelin proteins, S100B, and autoantibodies to them and serum levels of blood natriuretic peptide in patients with different categories of "normal" arterial BP and hypertension. The relationship between blood levels of the above factors and normotony, pre-hypertension, and hypertension in the examined groups was analyzed. The results suggest that the studied molecular factors can serve as potential predictors of arterial hypertension and used for personalized hypertension risk assessment.
Asunto(s)
Biomarcadores/sangre , Hipertensión/sangre , Prehipertensión/sangre , Adulto , Angiotensina II/sangre , Presión Sanguínea/fisiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Subunidad beta de la Proteína de Unión al Calcio S100/sangreRESUMEN
The content of S100b protein, HLDF24 peptide, and autoantibodies to these factors in blood serum was measured in healthy individuals (35-64-year-old men and women) with various levels of "normal" BP. Significant differences in the amount of these molecular factors were found in individuals with various categories of BP. We revealed age-related and gender differences in the content of molecular factors in the serum. Our results indicate that variations in the concentration of S100b, HLDF24, and autoantibodies to these factors in blood serum from adult people can serve as a reliable criterion for the risk of arterial hypertension.
Asunto(s)
Autoanticuerpos/sangre , Hipertensión/sangre , Proteínas de Neoplasias/sangre , Subunidad beta de la Proteína de Unión al Calcio S100/sangre , Adulto , Biomarcadores/sangre , Femenino , Voluntarios Sanos , Humanos , Hipertensión/inmunología , Masculino , Persona de Mediana Edad , Fragmentos de Péptidos/sangreRESUMEN
The dynamics of long-term memory retrieval on the 1st and 5th days after rat training in spatial Morris water maze and snail conditioned taste aversion models was studied. It was found that animals trained for several days displayed stable and high level of memory retrieval both on 1st and on 5th days after training. Under conditions of single-session training the rate of memory retrieval in snails and rats on the 5th day was higher than on the 1st day after training. It has been proposed that spontaneous enhancement of habit retrieval during 5-days time interval after training is a result of "lingering" memory consolidation processes, which includes trace reorganization in particular molecular and morphological changes in animal brain neurons.
Asunto(s)
Caracoles Helix/fisiología , Aprendizaje por Laberinto/fisiología , Memoria a Largo Plazo/fisiología , Animales , Estimulación Eléctrica , Hipocampo/fisiología , Masculino , Neuronas/fisiología , Ratas , Ratas Wistar , Percepción Espacial/fisiología , Percepción del Gusto , Factores de TiempoRESUMEN
We studied the effects of NMDA receptor antagonist MK-801 on the storage and reconsolidation of spatial memory in Morris water maze in adult rats. MK-801 (50 µg/kg) administered 24 h after the completion of training was shown to improve the resistance of spatial memory to spontaneous extinction, while reminder against the background of MK-801 suppresses its ameliorating effect on memory storage. The detected behavioral effects of MK-801 persisted over 60 days after administration and can be associated with its influence on coupled neurogenesis/apoptosis processes induced during memory trace formation in adult animals.
Asunto(s)
Maleato de Dizocilpina/farmacología , Aprendizaje por Laberinto/efectos de los fármacos , Memoria/efectos de los fármacos , Receptores de N-Metil-D-Aspartato/antagonistas & inhibidores , Percepción Espacial/efectos de los fármacos , Animales , Apoptosis/efectos de los fármacos , Apoptosis/fisiología , Masculino , Aprendizaje por Laberinto/fisiología , Memoria/fisiología , Neurogénesis/efectos de los fármacos , Neurogénesis/fisiología , Ratas , Ratas Wistar , Percepción Espacial/fisiología , Estadísticas no ParamétricasRESUMEN
We studied the relationships between the blood serum levels of human leukemia differentiation factor HLDF, idiotypic and anti-idiotypic antibodies to HLDF, and clinical indicators of cardiovascular function in apparently healthy individuals and patients with essential hypertension and cerebral hypertensive crisis. Markedly reduced HLDF levels and anti-HLDF antibody titers were found in the blood of the examined patients. Correlations between HLDF levels, duration of hypertension, and systolic and diastolic BP were revealed. These findings suggest that the studied molecular factors are involved in the mechanisms of BP regulation under normal conditions and during hypertension development. The protein HLDF and anti-HLDF antibodies can be considered as biomarkers for early diagnosis of hypertension and its cerebral complications.
Asunto(s)
Anticuerpos/inmunología , Presión Sanguínea/fisiología , Hipertensión/diagnóstico , Idiotipos de Inmunoglobulinas/inmunología , Hemorragia Intracraneal Hipertensiva/diagnóstico , Proteínas de Neoplasias , Anciano , Anticuerpos/sangre , Biomarcadores/sangre , Estudios de Casos y Controles , Ensayo de Inmunoadsorción Enzimática , Hipertensión Esencial , Humanos , Hipertensión/sangre , Hipertensión/complicaciones , Hipertensión/fisiopatología , Hemorragia Intracraneal Hipertensiva/sangre , Hemorragia Intracraneal Hipertensiva/etiología , Hemorragia Intracraneal Hipertensiva/fisiopatología , Persona de Mediana Edad , Proteínas de Neoplasias/sangre , Proteínas de Neoplasias/inmunología , Proteínas de Neoplasias/fisiología , Estadísticas no ParamétricasRESUMEN
The effects of serotonin and glutamate on c-fos expression and c-Fos colocalization with DNA were immunohistochemically studied in defense behavior command neurons R-LPa2-3 in snail Helix lucorum. Simultaneous neurotransmitter application resulted in increased c-Fos-immunoreactivity and colocalization with DNA-specific stain Hoechst 33342 in LPa2 and RPa2 neurons with specific dynamics for each identified cell. In the nuclei of LPa3 and RPa3 neurons, neurotransmitter application did not significant change the c-Fos level. These findings are indicative of specific spatiotemporal changes in c-fos expression and c-Fos colocalization with DNA in investigated neurons of edible snail under the influence of neurotransmitters.
Asunto(s)
Núcleo Celular/metabolismo , ADN/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Neuronas/metabolismo , Neurotransmisores/farmacología , Proteínas Proto-Oncogénicas c-fos/metabolismo , Animales , Bencimidazoles , Ácido Glutámico/farmacología , Inmunohistoquímica , Microscopía Fluorescente , Serotonina/farmacología , CaracolesRESUMEN
The expression of mRNA of genes involved in neurogenesis and apoptosis (Apaf1, Ascl1, Bax, Bcl2, Casp3, Casp8, Casp9, Dffb, Myh10, Naip2, Napa, Notch2, Numb, Pura, S100a6, Tnf) in the prefrontal cortex, hippocampus, and cerebellum was studied in adult rats. The content of mRNA of these genes (except Apaf1) was several-fold higher in the cerebellum than in the hippocampus and brain cortex. In the hippocampus, the expression of Apaf1 was significantly lower than in the prefrontal cortex, while the expression of Ascl1, Pura, S100b, and Tnf was higher. Regional differences in the direction, strength, and numbers of significant correlations between the expression of the studied genes were detected. Documented differences in gene expression were regarded as validation of the structural and functional cooperation of neurogenesis and apoptosis at the molecular genetic level.
Asunto(s)
Apoptosis/fisiología , Encéfalo/metabolismo , Regulación de la Expresión Génica/fisiología , Neurogénesis/fisiología , ARN Mensajero/metabolismo , Animales , Apoptosis/genética , Fluorometría , Masculino , Neurogénesis/genética , ARN Mensajero/genética , Ratas , Ratas Wistar , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Estadísticas no ParamétricasRESUMEN
The effects of Ro 25-6981 (selective NMDA receptor blocker) in a dose stimulating neurogenesis on repeated learning, reversal learning, and memory reconsolidation were studied in adult rats in Morris water maze. Ro 25-6981 facilitated repeated learning 13 days after injection, but did not influence reversal learning. The blocker injected directly before reminder did not disturb repeated learning and reversal learning in Morris water maze. These effects of Ro 25-6981 on the dynamics of repeated learning seemed to be due to its effects on neurogenesis processes in adult brain.
Asunto(s)
Aprendizaje/efectos de los fármacos , Memoria a Largo Plazo/efectos de los fármacos , Neurogénesis/efectos de los fármacos , Fenoles/farmacología , Piperidinas/farmacología , Percepción Espacial/efectos de los fármacos , Animales , Aprendizaje/fisiología , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Memoria a Largo Plazo/fisiología , Neurogénesis/fisiología , Ratas , Ratas Wistar , Percepción Espacial/fisiología , Estadísticas no ParamétricasRESUMEN
Effect of administration of selective N-methyl-D-aspartate (NMDA) receptor antagonist Ro 25-6981 on learning and memory in a dose which is known to stimulate neoneurogenesis was assessed in adult rats with different abilities to formation of spatial skills in different time periods after the antagonist injection. Wistar male rats were trained to find hidden platform in the Morris water maze for 5 consecutive days. Rats' learning ability for spatial skill formation was evaluated depending on platform speed achievements. In re-training sessions (cues and platform location changed), it was found that all rats received Ro 25-6981 13 days before the re-training demonstrated impaired spatial memory. At the same time the inhibitor injected 29 days before re-training selectively facilitated the formation of spatial skill in animals with initially low learning abilities.
Asunto(s)
Aprendizaje por Laberinto/efectos de los fármacos , Memoria/efectos de los fármacos , Neurogénesis , Fenoles/farmacología , Piperidinas/farmacología , Receptores de N-Metil-D-Aspartato/antagonistas & inhibidores , Animales , Relación Dosis-Respuesta a Droga , Masculino , Trastornos de la Memoria/inducido químicamente , Fenoles/efectos adversos , Piperidinas/efectos adversos , Ratas , Factores de TiempoRESUMEN
The effect of MK-801, an antagonist to NMDA-glutamate receptors, on reconsolidation of olfactory discrimination task in rats and taste discrimination in edible snails was examined. Twenty-four hours after conditioning, the animals received a single systemic injection of MK-801 followed by a reminding conditional stimulus. Disturbances in retrieval of the acquired task were observed 10 days after injection followed by a reminding procedure. Repeated conditioning of these animals did not restore the task. Injection of MK-801 without reminding stimulation had no effect on task retention. Thus, disturbances of NMDA-dependent reconsolidation of the associative memory in animals of different taxonomic groups irreversibly eliminated long-term memory.
Asunto(s)
Amnesia/fisiopatología , Asociación , Aprendizaje Discriminativo/efectos de los fármacos , Maleato de Dizocilpina/farmacología , Memoria a Largo Plazo/efectos de los fármacos , Receptores de N-Metil-D-Aspartato/antagonistas & inhibidores , Olfato , Gusto , Animales , Condicionamiento Psicológico , Aprendizaje Discriminativo/fisiología , Maleato de Dizocilpina/administración & dosificación , Masculino , Memoria a Largo Plazo/fisiología , Ratas , Ratas Wistar , Caracoles , Estadísticas no ParamétricasRESUMEN
Complex evaluation neurotrophic protein S100b, differentiation factor HLDF, idio-and antiidiotypic antibodies against these proteins in patient sera with hypertension-induced cerebrovascular disorders was performed by ELISA. In patients with essential hypertension, cerebral hypertensive crisis and ischemic stroke S100b and anti-S100b concentration was found to be higher, whereas HLDF and anti-HLDF ones were lower compared with control. Different dynamics of S100b, HLDF content and antibody level was shown within 21 days of observation. These findings may be useful in further diagnostic and prognostic studies of hypertension-induced cerebrovascular disorders.
Asunto(s)
Trastornos Cerebrovasculares/sangre , Trastornos Cerebrovasculares/etiología , Hipertensión/sangre , Hipertensión/complicaciones , Anciano , Autoanticuerpos/sangre , Trastornos Cerebrovasculares/diagnóstico , Femenino , Humanos , Hipertensión/diagnóstico , Masculino , Persona de Mediana Edad , Proteínas de Neoplasias/sangre , Factores de Crecimiento Nervioso/sangre , Subunidad beta de la Proteína de Unión al Calcio S100 , Proteínas S100/sangreRESUMEN
Stimulations of different sensory modalities result in selective activation of second messengers and genes controlled by them in defensive behavior command neurons (LPl-1 and RPl-1) in edible snail. Excitation induced by stimulation of chemoreceptors of snail head results in cAMP accumulation in command neurons and induction of associated transcriptional factors of immediate early gene C/EBP, whereas regulating mechanisms of another sensory input mediating excitation after tactile head stimulation, involve protein kinase C and associated transcriptional factor SRF. These findings reflect specific features of postsynaptic processes providing excitation of different sensory modalities converging to defensive behavior command neurons in edible snails.
Asunto(s)
Potenciales Postsinápticos Excitadores/fisiología , Caracoles Helix/fisiología , Animales , Proteínas Potenciadoras de Unión a CCAAT/metabolismo , Proteínas Potenciadoras de Unión a CCAAT/fisiología , AMP Cíclico/metabolismo , AMP Cíclico/fisiología , Proteína 1 de la Respuesta de Crecimiento Precoz/metabolismo , Proteína 1 de la Respuesta de Crecimiento Precoz/fisiología , Caracoles Helix/metabolismo , Modelos Biológicos , Plasticidad Neuronal/fisiología , Neuronas/metabolismo , Neuronas/fisiología , Proteína Quinasa C/metabolismo , Proteína Quinasa C/fisiología , Factor de Respuesta Sérica/metabolismo , Factor de Respuesta Sérica/fisiologíaRESUMEN
A cross-sectional mass epidemiological survey of 18,320 urban and rural citizens of the Republic of Tadjikistan revealed 31 patients with orbital tumors, of which lacrimal neoplasms were determined in 4 (0.022% in the general population and 12.9% of the identified orbital tumors). According to the referral data, the prevalence of lacrimal neoplasms was 1.03% of all the tumors of the organ of vision and 5.26% of the orbital neoplasms. Epithelial tumors were more common (52%), their malignant forms dominated over benign ones (55.7% versus 44.3%). Inflammatory processes (22.6%) as acute and chronic dacryoadenitis (9.5%) and pseudotumors (13.1) were the second most common conditions. Lymphoid tissue tumors (13.6%), cystoid masses (8.6%), and neoplasms of unclear genesis (1.4%) were noticeably less prevalent. The severest difficulties in recognizing lacrimal epithelial tumors were to clinically and morphologically identify what determined the specific features of the lacrimal structure and evident structural polymorphism. With the higher grade of anaplasia, the likelihood of a recurrence of a tumor and the rate of its growth increased (r = +0.83). The survival rates closely correlated with the higher rates of recurrent adenocarcinoma and adenocystic cancer (r = -0.87).
Asunto(s)
Neoplasias del Ojo/epidemiología , Aparato Lagrimal , Adulto , Diagnóstico Diferencial , Neoplasias del Ojo/diagnóstico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Morbilidad , Vigilancia de la Población , Estudios Retrospectivos , Tayikistán/epidemiologíaRESUMEN
The effects of two 5-membered (SP5, SP6) endogenous synthetic peptide fragments of protein S100b on the course of regenerative-reparative processes in the corneas of Wistar rats were morphologically studied after making a graduated injury. Conjunctival or endonasal injection of the peptides was made at two concentrations of 10(-6) and 10(-8) M. The study peptides were found to have a modulating effect on regenerative-reparative processes regardless of the route of administration and to induce accelerated and qualitative corneal wound healing as compared with the controls. The specific feature of SP5 was the formation of a fibroblastic membrane. When SP5 was injected at a concentration of 10(-6) M, the membrane was more pronounced and occupied the whole area of keratectomy whereas when this peptide was administered at a concentration of 10(-8) M, its formation was observed in the deep and middle corneal layers. The most marked effect of SP6 revealed during the study was the formation of newly-formed vessels over the entire wound surface independently of the concentration of the injected substance. Of the two study peptide fragments, SP5 is, in the authors' opinion, promising for clinical application. Significant keratocytic proliferation noted in the use of SP5 at a concentration of 10(-6) M may be used to accelerate scarring when the sclera and cutaneous covering are damaged. The effects detected with administration of SP6 at two concentrations were regarded as negative as they did not answer the purpose set during the study performed.