RESUMO
Chronic mild stress (CMS) is a widely accepted animal model relevant to depression that among other consequences, is chiefly known to induce anhedonia, often assessed as decreased preference for sucrose solution. CMS is also known to affect cognition, particularly memory tasks. In this study we have employed the multiple-trial inhibitory avoidance memory task (MTIA) to assess CMS effects on memory acquisition and retrieval. MTIA consists of repeated exposures to the unconditioned stimulus until a learning criterion is reached. Wistar rats underwent CMS for 5 weeks, and sucrose consumption was assessed once a week. At the end of CMS, animals were evaluated in the MTIA task. Overall decreased sucrose solution preference was highly variable. Further analyses showed that a subset of animals expressed resilience while another subset was sensitive to stress. CMS did not affect the number of acquisition sessions before reaching criterion or retrieval latency of MTIA task in neither sensitive nor resilient groups. Although tasks that assess learning ability in animal models relevant to depression indicate cognitive deficits, the ability to learn the association between compartment crossing and the aversive electric foot shock, which is strongly dependent on emotional aspects, was intact.
Assuntos
Aprendizagem da Esquiva , Rememoração Mental , Estresse Psicológico/psicologia , Animais , Ingestão de Alimentos , Estimulação Elétrica , Masculino , Ratos , SacaroseRESUMO
Sleep deprivation impairs performance in emotional memory tasks, however this effect on memory is not completely understood. Possible mechanisms may involve an alteration in neurotransmission systems, as shown by the fact that many drugs that modulate neural pathways can prevent memory impairment by sleep loss. Gastrin releasing peptide (GRP) is a neuropeptide that emerged as a regulatory molecule of emotional memory through the modulation of other neurotransmission systems. Thus, the present study addressed the effect of intraperitoneal (IP) administration of bombesin (BB) (2.5, 5.0 and 10.0µg/kg), a GRP agonist, on the performance of Wistar rats in a multiple trail inhibitory avoidance (MTIA) task, after sleep deprivation, using the modified multiple platforms method (MMPM). Sleep deprived animals exhibited acquisition and retention impairment that was not prevented by BB injection. In addition, non-sleep deprived animals treated with BB before and after the training session, but not before the test, have shown a retention deficit. In summary, BB did not improve the memory impairment by sleep loss and, under normal conditions, produced a memory consolidation deficit.
Assuntos
Bombesina/farmacologia , Transtornos da Memória/induzido quimicamente , Memória/efeitos dos fármacos , Privação do Sono , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Modelos Animais de Doenças , Masculino , Fragmentos de Peptídeos/farmacologia , Ratos Wistar , Privação do Sono/tratamento farmacológicoRESUMO
One of the main hallmarks of Alzheimer's disease includes the neurofibrillary tangles formation produced by hyperphosphorylation of the Tau protein, whose expression is putatively regulated by the ovarian hormones estradiol and progesterone. Hippocampus is a brain region that participates in many functions related to learning and memory; in addition, it is abundant in both estradiol and progesterone receptors. In this study, we explore the expression of Tau hyperphosphorylation at hippocampus and the performance of rats in an autoshaping learning task at 5, 10 and 15 months after the ovaries removal. In these animals, ovariectomy was performed at 3 months of age. These data were compared with those derived from intact rats at 8, 13 and 18 months old. A clear decrease in the number of conditioned responses of both intact and ovariectomized rats in the autoshaping learning task was observed. The interaction of both factors confirms that, in this test, learning varies depending on aging and the presence or absence of ovaries. A progressive increase in hippocampal Tau phosphorylation at Ser-396 was observed in either intact or ovariectomized rats. Interestingly, an interaction between the analyzed factors shows that such hyperphosphorylation was potentiated by the absence of ovaries. These results emphasize the importance of aging and the lack of ovarian hormones for an associative learning test and for the expression of one of the most important hallmarks of Alzheimer's disease.
Assuntos
Envelhecimento/fisiologia , Região CA1 Hipocampal/metabolismo , Ovariectomia , Proteínas tau/metabolismo , Análise de Variância , Animais , Aprendizagem por Associação/fisiologia , Feminino , Regulação da Expressão Gênica/fisiologia , Fosforilação , Ratos , Ratos WistarRESUMO
Estrogen depletion due to aging, surgery or pathological events can cause a multitude of problems, including neurodegenerative alterations. In rodents without ovaries, 17-beta estradiol (E2) has been shown to produce beneficial effects on cognition, stimulating brain regions (e.g., the neocortex, hippocampus and amygdala) related to cognition and learning. Another treatment that stimulates these brain regions is an enriched environment (EE), which is a complex set of external factors in the immediate surroundings that facilitates greater stimulation of sensorial, cognitive and motor circuits of the brain. The aim of the present study was to test, using an animal model of ovariectomy-induced impairment of memory, the relative effect of E2 (with a time-released pellet; 1 µg/rat/day), EE exposure and a combination of both treatments. Experimental and control groups were submitted to two memory tests 18 weeks post-surgery: the autoshaping learning task (ALT) for measuring associative learning and the novel object recognition test (NORT) for evaluating short- and long-term memory. To assess potential motor impairments caused by treatments, all rats were tested after the ALT in an automatic activity counter. Results from ALT show that the ovariectomy blocked the conditioned responses displayed, an effect rescued by chronic treatment with estrogen or EE exposure. The combination of both treatments did not improve the results obtained separately. In the NORT, the exploration time for recognizing a novel object was similar in the short run with all groups, but greater in the long run with hormone administration or EE exposure. As with the ALT, in the NORT there was no improvement shown by the combination treatment. These data were not masked by changes in spontaneous activity because this parameter was not modified in the rats by either treatment. Possible action mechanisms are proposed, taking into account the role of corticosterone and BDNF on cognition.
Assuntos
Aprendizagem por Associação/efeitos dos fármacos , Cognição/efeitos dos fármacos , Meio Ambiente , Estradiol/farmacologia , Estrogênios/farmacologia , Animais , Sistemas de Liberação de Medicamentos , Comportamento Exploratório/efeitos dos fármacos , Feminino , Atividade Motora/efeitos dos fármacos , Ovariectomia , Ratos , Ratos Sprague-Dawley , Estatísticas não ParamétricasRESUMO
OBJECTIVE: To study the association of HLA-B27 with IgG antibodies to different enterobacterial HSP60s in patients with ankylosing spondylitis (AS). METHODS: IgG antibodies to 60 kDa enterobacterial HSPs were determined by ELISA in paired samples of sera and synovial fluid from 21 HLA-B27+ ankylosing spondylitis (AS) patients; and in sera from 32 HLA-B27+ AS patients, 35 HLA-B27+ healthy relatives of AS patients, and 60 HLA-B27- healthy individuals with no family members with AS. RESULTS: HLA-B27+ patients and healthy individuals showed significantly higher IgG antibody levels to recombinant enterobacterial HSP60s than HLA-B27- healthy controls. The levels of anti-HSP60Sf and anti-HSP60Ec antibodies correlated with disease activity and anti-HSP60Ec antibodies with male gender. No association between enterobacterial HSP60 antibody levels and disease duration was observed. All groups had lower levels of IgG antibodies to rHSP60 from Streptococcus pyogenes (rHSP60 Spy). In paired samples of sera and synovial fluid from B27+ patients, IgG antibodies to enterobacterial HSP60s were detected, but in significantly higher levels in sera than in synovial fluid. The anti-rHSPSpy IgG response in these samples was lower and similar in the three groups. CONCLUSIONS: A correlation was found between HLA-B27 and the response to recombinat enterobacterial HSP60s. This response could be associated with disease activitir and gender in some proteins and the presence eof IgG antibodies to these proteins in synovial fluid could be associated with the inflammatory process and initiation of AS.
Assuntos
Chaperonina 60/imunologia , Infecções por Enterobacteriaceae/imunologia , Antígeno HLA-B27/imunologia , Espondilite Anquilosante/imunologia , Líquido Sinovial/imunologia , Adolescente , Adulto , Anticorpos Antibacterianos/sangue , Chaperonina 60/biossíntese , Enterobacteriaceae/imunologia , Infecções por Enterobacteriaceae/sangue , Infecções por Enterobacteriaceae/complicações , Feminino , Antígeno HLA-B27/genética , Humanos , Indígenas Norte-Americanos/genética , Masculino , México , Pessoa de Meia-Idade , Proteínas Recombinantes/imunologia , Espondilite Anquilosante/sangue , Espondilite Anquilosante/microbiologia , Líquido Sinovial/microbiologia , Adulto JovemRESUMO
In the present study the acetylcholinesterase (AChE) inhibition and acute toxicity of two succinic acid derivatives were compared with tacrine. Administration of a single dose of each of two succinic acid derivatives produced a time and dose-dependent inhibition of brain AChE activity. Although the magnitude of the cholinergic effects observed with the two succinic acid derivatives was similar to that seen with tacrine and other AChE inhibitors, the toxicity study showed that the new inhibitors have less adverse side effects.
Assuntos
Acetilcolinesterase/metabolismo , Ácido Succínico/química , Ácido Succínico/farmacologia , Animais , Dose Letal Mediana , Masculino , Camundongos , Ácido Succínico/toxicidadeRESUMO
The sensory pudendal nerve (SPN) was stimulated in decerebrate female cats. Spikes of single Ia muscle spindle afferents from the medial gastrocnemius (MG) muscle were recorded in dorsal root filaments. Electroneurography (ENG) was recorded in a cut nerve filament to the MG muscle; MG electromyography (EMG) was also recorded. Single shock to SPN induced discharges of small ENG spikes (SS) with similar amplitude to that of gamma spikes elicited by ventral root stimulation. Thus SS were identified as gamma spikes. The latency of the gamma discharge was approximately 15 ms. As expected, the onset of the gamma discharge preceded a discharge of Ia spikes; the time difference between both discharges was approximately 5 ms. After the initial bursts, the Ia and the gamma activities paused during 20-30 ms but later increased again to last approximately 1 s. After the shock, the EMG activity was depressed during approximately 50 ms; later, motor-unit spikes may show transient activation. Thus the onset of the gamma activation preceded the activation of motor units (gamma-->alpha link). Trains of shocks (1 or 100 Hz) to SPN induced a sustained increase in the frequency of gamma spikes, Ia spikes, and motor units that outlasted the train by 20-120 s. The sustained firing of Ia fibers might trigger or help to trigger and maintain the response of alpha-motoneurons.
Assuntos
Potenciais de Ação/fisiologia , Ritmo alfa/métodos , Fibras Nervosas/fisiologia , Vias Aferentes/fisiologia , Animais , Gatos , Estado de Descerebração/fisiopatologia , Estimulação Elétrica/métodos , Eletromiografia/métodos , FemininoRESUMO
Axons from receptors in the cat vaginal wall run in the sensory pudendal nerve (SPN), and brief (<10 s) vaginal probing (VP) in the decerebrate cat produces a long-lasting (>1 min) contraction of the triceps surae (TS) muscles. The aim of the present project was to find out whether brief SPN stimulation also produces sustained TS response and, eventually, to study the mechanisms involved in it. Decerebrate female cats were used. In some cats, TS electromyography (EMG) and tension response were recorded; stimulation of left SPN with single or repetitive trains of shocks produced a bilateral TS response that outlasted the stimulus >1 min as VP did. In paralyzed cats (pancuronium; Panc), intracellular recordings were made from hind limb motoneurons (MNs). SPN stimulation produced a depolarization
Assuntos
Membro Posterior/inervação , Neurônios Motores/fisiologia , Pelve/inervação , Potenciais de Ação/efeitos dos fármacos , Animais , Gatos , Estado de Descerebração , Estimulação Elétrica , Eletromiografia , Eletrofisiologia , Feminino , Neurônios Motores gama/fisiologia , Contração Muscular/fisiologia , Músculo Esquelético/fisiologia , Fenômenos Fisiológicos do Sistema Nervoso , Fármacos Neuromusculares não Despolarizantes/farmacologia , Pancurônio/farmacologia , Paralisia/induzido quimicamente , Paralisia/fisiopatologiaRESUMO
In decerebrate cats, controlled mechanical stimulation of the perivulvar skin, the vaginal wall or the cervix uteri induced visible hind limb extension. Pressing on the cervix uteri produced the greater response. To quantify these responses, the EMG activity and the tension developed by the normally inserted triceps surae muscles were recorded. The activity induced in these muscles by stimulation of the genital canal outlasted the stimulus by many seconds or a few minutes. These effects disappeared after spinalization at the T12 level. We propose that stimulation of the vaginal canal in the female cat may induce bistability of triceps surae motoneurones.