RESUMO
Cardiomyopathic hamsters (CMH) develop heart disease early in life which leads to congestive heart failure and death as these hamsters age. We have previously shown that living in constant light or other non-24-h light-dark (LD) cycles can increase longevity in these hamsters, and the current experiment examined potential mechanisms for this effect. Thus, CMH were orchidectomized, pinealectomized, or given melatonin treatment and then placed on either 1:23 or 1:23.6 LD cycles. Orchidectomy had no effect on longevity in either LD cycle, but in 1:23.6 it did lead to death with a greater degree of heart failure. On the other hand, pinealectomy of 1:23 CMH led to changes in life span similar to those produced by placing the hamsters in 1:23.6. Moreover, melatonin implant treatment of CMH in 1:23.6 led to changes in life span that were similar to those caused by life in 1:23, at least over the first half of the survival curves. Thus, it appears that the pineal gland and melatonin may be involved in mediating the effects of non-24-h LD cycles, whether these effects are beneficial or detrimental. In addition, the testes and testosterone appear to have no role in mediating these effects. These data suggest that inhibition, rather than stimulation, of pineal function might be beneficial for those with congestive heart failure, but further experiments are necessary to clarify when during the disease process potential treatments might be helpful.
Assuntos
Cardiomiopatias/fisiopatologia , Insuficiência Cardíaca/fisiopatologia , Longevidade/fisiologia , Glândula Pineal/fisiologia , Animais , Ritmo Circadiano/fisiologia , Cricetinae , Masculino , Melatonina/fisiologiaRESUMO
Pyridostigmine bromide (PB) is a reversible, peripherally active inhibitor of acetylcholinesterase (AChE) activity, and is recommended by the military as a pretreatment against potential nerve gas exposure. Recent evidence suggests that exposure to inescapable stressors allows PB to cross the blood-brain barrier, and thereby affect central AChE activity in mice. Here, we evaluated the functional impact of a stress/PB treatment interaction on acoustic startle responding and plasma butyrylcholinesterase (BuChE) activity in male Sprague-Dawley rats. To model the treatment protocol used by the military, PB was delivered in the drinking water of rats for 7 consecutive days. The morning after the start of PB treatment, and for the next 6 days, half the rats were exposed to 1 h of supine restraint stress. We therefore employed a 2 x 2 (stress x PB treatment) between-groups design. Exposure to supine stress alone induced a persistent decrease in plasma BuChE activity. Further decreases in BuChE activity were not observed in rats exposed to supine restraint and PB treatment. Exposure to stress also induced an exaggerated startle response, evident on the last day of stress and 24 h after stressor cessation. Treatment with PB alone produced an exaggerated startle response over the same time period, albeit to a lesser degree. Although treatment with PB concurrent with stress did not produce further changes in either BuChE activity or acoustic startle responding, stress-induced alterations in drinking behavior (and thereby the dose of PB ingested) may have affected these results. Persistent stress-induced reductions in BuChE activity may increase the risk of adverse reactions to cholinomimetics.
Assuntos
Butirilcolinesterase/sangue , Inibidores da Colinesterase/farmacologia , Brometo de Piridostigmina/farmacologia , Reflexo de Sobressalto/fisiologia , Estresse Psicológico/enzimologia , Estresse Psicológico/psicologia , Estimulação Acústica , Animais , Corticosterona/sangue , Ingestão de Líquidos/efeitos dos fármacos , Ingestão de Líquidos/fisiologia , Masculino , Ratos , Ratos Sprague-Dawley , Reflexo de Sobressalto/efeitos dos fármacos , Restrição FísicaRESUMO
Chronic fatigue syndrome, which can occur after acute infection and last for years, is characterized by severe and persistent fatigue. Others have reported decreases in mouse running activity following infection and have suggested this may provide an animal model for studying chronic fatigue. Voluntary running is a highly motivated activity in mice, which will often run 5-7 mi/day in our laboratory. Following 2 weeks of acclimation to running wheels with food and water available ad lib, female BALB/c mice received 0.2-mL tail vein injections of killed Brucella abortus (BA) or saline vehicle. Subsequently the effects on voluntary running and grooming behavior were determined. Injection of BA caused an immediate large decrease in running and a lack of grooming. Vehicle injections produced no changes in behavior. After the first several days of reduced running behavior, levels of running and grooming slowly returned back to normal over the next 2-4 weeks, with substantial individual differences in the rate of recovery. The pattern of running during recovery was intriguing in that BA mice first ran at normal levels just after the lights went out, but they stopped after only 1-2 h. As recovery proceeded, they gradually increased the duration of the running bout during the night. Because this model uses voluntary exertion and the ability to run for longer periods of time characterizes recovery, the model may be a good one for studying the biologic underpinnings of chronic fatigue.
Assuntos
Brucella abortus , Brucelose/fisiopatologia , Modelos Animais de Doenças , Síndrome de Fadiga Crônica/fisiopatologia , Atividade Motora/fisiologia , Animais , Ritmo Circadiano/fisiologia , Citocinas/fisiologia , Feminino , Asseio Animal/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos BALB CAssuntos
Acetilcolina/metabolismo , Química Encefálica/efeitos dos fármacos , Inibidores da Colinesterase/toxicidade , Brometo de Piridostigmina/toxicidade , Estresse Fisiológico/metabolismo , Acetilcolinesterase/efeitos dos fármacos , Animais , Gânglios da Base/efeitos dos fármacos , Gânglios da Base/enzimologia , Comportamento Animal/efeitos dos fármacos , Inibidores da Colinesterase/efeitos adversos , Inibidores da Colinesterase/farmacologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Resistência a Medicamentos/genética , Eletrochoque , Predisposição Genética para Doença , Variação Genética , Contração Muscular/efeitos dos fármacos , Proteínas do Tecido Nervoso/antagonistas & inibidores , Síndrome do Golfo Pérsico/induzido quimicamente , Síndrome do Golfo Pérsico/fisiopatologia , Prosencéfalo/efeitos dos fármacos , Prosencéfalo/enzimologia , Brometo de Piridostigmina/efeitos adversos , Brometo de Piridostigmina/farmacologia , Ratos , Ratos Endogâmicos WKY , Ratos Sprague-Dawley , Salivação/efeitos dos fármacos , Estresse Fisiológico/genéticaRESUMO
To examine the degree and nature of cognitive impairments in chronic fatigue syndrome, a comprehensive neuropsychological battery was given to patients with chronic fatigue syndrome, multiple sclerosis, depressed patients, and healthy controls. The battery included tests of attention and concentration, information processing speed, verbal and visual memory, intellectual ability, and concept formation. Measures of depression and anxiety were also obtained. The chronic fatigue syndrome group did not differ from the depressed group in overall neuropsychological performance, but differed from the multiple sclerosis and control groups. The most significant impairment was in information processing speed in the chronic fatigue syndrome group. Depression and anxiety were not related to neuropsychological performance. The influence of reduced information processing on other areas of cognition is discussed.
Assuntos
Transtornos Cognitivos/etiologia , Transtorno Depressivo/complicações , Síndrome de Fadiga Crônica/complicações , Esclerose Múltipla/complicações , Testes Neuropsicológicos , Adulto , Transtornos de Ansiedade/diagnóstico , Transtornos de Ansiedade/psicologia , Encéfalo/fisiopatologia , Transtornos Cognitivos/diagnóstico , Transtorno Depressivo/fisiopatologia , Síndrome de Fadiga Crônica/fisiopatologia , Humanos , Esclerose Múltipla/fisiopatologia , Análise e Desempenho de TarefasRESUMO
Troops in the Persian Gulf War have registered complaints consistent with CNS dysfunction that emerged after returning from the Gulf. A common experience among Persian Gulf War veterans was exposure to pyridostigmine bromide (PB) for prophylaxis against nerve gas exposure. To determine whether PB causes emergent CNS dysfunction, Wistar-Kyoto (WKY) and Sprague-Dawley (SD) rats were given PB for 7 consecutive days in their drinking water. The WKY, but not the SD, rats exhibited a delayed-onset, persistently exaggerated startle response. The WKY rats exhibited exaggerated startle responses that appeared 15 days after the end of PB treatment and were still evident 22 days after the end of treatment. Both the duration and the magnitude of the exaggerated startle responses were related to the dosage of PB. The PB-treated rats exhibited normal short-term and long-term habituation. However, exaggerated startle responses were related to the development of enhanced short-term sensitization. Treating the rats for a second time, 7 weeks after the end of the first PB treatment, induced an exaggerated startle response that appeared sooner and dissipated faster than was evident after the first PB treatment. Inasmuch as the WKY rat has inherently low butyrylcholinesterase activity, a scavenger for PB, these results suggest that prophylactic PB may influence CNS function in individuals with low butyrylcholinesterase activity. Elaboration of the factors that mediate enhanced sensitization in the WKY rat may provide insight into some of the complaints registered by veterans of the Persian Gulf War.
Assuntos
Inibidores da Colinesterase/farmacologia , Parassimpatomiméticos/farmacologia , Brometo de Piridostigmina/farmacologia , Reflexo de Sobressalto/efeitos dos fármacos , Animais , Butirilcolinesterase/sangue , Doenças do Sistema Nervoso Central/sangue , Doenças do Sistema Nervoso Central/induzido quimicamente , Inibidores da Colinesterase/efeitos adversos , Humanos , Masculino , Atividade Motora/efeitos dos fármacos , Limiar da Dor/efeitos dos fármacos , Síndrome do Golfo Pérsico/induzido quimicamente , Brometo de Piridostigmina/efeitos adversos , Ratos , Ratos Endogâmicos WKY , Ratos Sprague-Dawley , Fatores de TempoRESUMO
Elevated basal plasma corticosterone concentrations have been observed for several days after the cessation of severe stress. In the present study, we examined whether or not the acute plasma corticosterone response to stress is necessary to elicit increased basal plasma corticosterone concentrations the following day. Pretreatment with metyrapone (100 m a g , intraperitoneal)1 h before inescapable stress (40 2mA tail shocks delivered over a 1-h period) (IS)blocked the acute plasma corticosterone response to IS. However, elevated basal plasma corticosterone concentrations still emerged the next day. These results suggest that the corticosterone response to stress, and its attendant feedback, are not necessary to produce persistent hypothalamic-pituitary-adrenal axis (HPAA) activation.