Aging sensitizes male mice to cognitive dysfunction induced by central HIV-1 gp120.

Although highly active antiretroviral therapy has led to improved prognosis and alleviation of some HIV-related disease complications, it has not provided complete protection against HIV-associated dementia. As the population of persons living with HIV grows older and aged persons represent a significant number of new infections, it is important to understand how HIV may affect the aged brain. In the current study, both adult and aged mice were treated with HIV gp120 and trained in a reference memory version of the water maze.

A drug-drug conditioning paradigm reveals multiple antipsychotic-nicotine interactions.

Clinical studies indicate a reciprocal impact between nicotine use and antipsychotic medications in patients with schizophrenia. The present study used a conditioned avoidance response (CAR) test (a behavioral test of antipsychotic effect) and examined the specific drug-drug interactions between nicotine and haloperidol or clozapine. Following acquisition of the avoidance response, rats were first tested under either vehicle, nicotine (0.

Drug-drug conditioning between citalopram and haloperidol or olanzapine in a conditioned avoidance response model: implications for polypharmacy in schizophrenia.

Patients with schizophrenia often have anxiety and depression, and thus are treated with multiple psychotherapeutic medications. This practice of polypharmacy increases the possibility for drug-drug interactions. However, the pharmacological and behavioral mechanisms underlying drug-drug interactions in schizophrenia remain poorly understood.

Inhibition of interleukin-6 trans-signaling in the brain facilitates recovery from lipopolysaccharide-induced sickness behavior.

Background: Interleukin (IL)-6 is produced in the brain during peripheral infection and plays an important but poorly understood role in sickness behavior. Therefore, this study investigated the capacity of soluble gp130 (sgp130), a natural inhibitor of the IL-6 trans-signaling pathway to regulate IL-6 production in microglia and neurons in vitro and its effects on lipopolysaccharide (LPS)-induced sickness behavior in vivo.

Methods: A murine microglia (BV.

A neurotoxic regimen of methamphetamine exacerbates the febrile and neuroinflammatory response to a subsequent peripheral immune stimulus.

Methamphetamine (MA) use is associated with activation of microglia and, at high doses, can induce neurotoxicity. Given the changes in the neuroinflammatory environment associated with MA, we investigated whether MA administration would interfere with the thermoregulatory and neuroinflammatory response to a subsequent peripheral immune stimulus. C57BL6/J mice were given four i.

Cognitive deficits in interleukin-10-deficient mice after peripheral injection of lipopolysaccharide.

Interleukin (IL)-10 is important for regulating inflammation but whether it protects against infection-related deficits in cognitive function is unknown. Therefore, the current study evaluated sickness behavior, hippocampal-dependent matching-to-place performance and several inflammatory cytokines and neurotrophins in wild-type (IL-10(+/+)) and IL-10-deficient (IL-10(-/-)) mice after i.p.

Neuroinflammation associated with aging sensitizes the brain to the effects of infection or stress.

The aging brain is characterized by a shift from the homeostatic balance of inflammatory mediators to a proinflammatory state. This increase in neuroinflammation is marked by increased numbers of activated and primed microglia, increased steady-state levels of inflammatory cytokines and decreases in anti-inflammatory molecules. These conditions sensitize the aged brain to produce an exaggerated response to the presence of an immune stimulus in the periphery or following exposure to a stressor.

Neonatal endotoxin exposure impairs avoidance learning and attenuates endotoxin-induced sickness behavior and central IL-1beta gene transcription in adulthood.

Infection during infancy, a time of critical neural development, may have long-term implications. Infection or exposure to an immune stimulus such as lipopolysaccharide (LPS) early in life leads to alterations in the reactivity of the hypothalamic-pituitary-adrenal axis (HPA) and febrile response in adulthood. Relatively few studies have assessed the behavioral and cognitive alterations induced by perinatal immune challenge.

Aging exacerbates depressive-like behavior in mice in response to activation of the peripheral innate immune system.

Exposure to peripheral infections may be permissive to cognitive and behavioral complications in the elderly. We have reported that peripheral stimulation of the innate immune system with lipopolysaccharide (LPS) causes an exaggerated neuroinflammatory response and prolonged sickness behavior in aged BALB/c mice. Because LPS also causes depressive behavior, the purpose of this study was to determine whether aging is associated with an exacerbated depressive-like response.

Neuroinflammation and disruption in working memory in aged mice after acute stimulation of the peripheral innate immune system.

Acute cognitive disorders are common in elderly patients with peripheral infections but it is not clear why. Here, we injected old and young mice with Escherichia coli lipopolysaccharide (LPS) to mimic an acute peripheral infection and separated the hippocampal neuronal cell layers from the surrounding hippocampal tissue by laser capture microdissection and measured mRNA for several inflammatory cytokines (IL-1 beta, IL-6, and TNFalpha) that are known to disrupt cognition. The results showed that old mice had an increased inflammatory response in the hippocampus after LPS compared to younger cohorts.

Interleukin-6 facilitates lipopolysaccharide-induced disruption in working memory and expression of other proinflammatory cytokines in hippocampal neuronal cell layers.

Proinflammatory cytokines inhibit learning and memory but the significance of interleukin-6 (IL-6) in acute cognitive deficits induced by the peripheral innate immune system is not known. To examine the functional role of IL-6 in hippocampus-mediated cognitive impairments associated with peripheral infections, C57BL6/J (IL-6(+/+)) and IL-6 knock-out (IL-6(-/-)) mice were trained in a matching-to-place version of the water maze. After an acquisition phase, IL-6(+/+) mice injected intraperitoneally with lipopolysaccharide (LPS) exhibited deficits in working memory.

Bacterial endotoxin-induced behavioral alterations in two variations of the Morris water maze.

Several studies report that lipopolysaccharide (LPS) or interleukin-1beta (IL-1beta) may affect behavior in a variety of learning tasks, including the Morris water maze (MWM), though the nature of these effects varies with testing parameters. The present study used C57BL/6J mice to evaluate the effect of a single intraperitoneal LPS injection 4 h prior to day 1 of testing, LPS before each day of testing, or saline prior to each test day, on performance in two variations of the MWM. In the first experiment, one that utilized a standard hidden platform, LPS clearly affected performance, as shown by increased latencies and greatly decreased swimming speeds.

Peripheral lipopolysaccharide administration impairs two-way active avoidance conditioning in C57BL/6J mice.

Peripheral administration of lipopolysaccharide (LPS) or interleukin-1 (IL-1) may lead to alterations of CNS function and behavioral changes designated "sickness behavior." Further, some experiments show evidence of LPS- and cytokine-mediated alterations in learning and memory. The current series of experiments examined the effects of a single or repeated intraperitoneal LPS injections, at a number of doses and time points before or after test sessions, on behavior in a two-way active avoidance conditioning paradigm.

Effects of intraperitoneal lipopolysaccharide on Morris maze performance in year-old and 2-month-old female C57BL/6J mice.

Several studies have shown that systemic lipopolysaccharide (LPS) or interleukin-1beta (IL-1beta) may affect performance in various learning tasks, including the Morris water maze. In the current study, female C57BL/6J mice, either 2 months or 1 year of age, were given 5 days of testing followed by 3 days of rest, and then three additional days of testing. Mice either received a single LPS injection on day 1 and saline on days 2-5, LPS injections on days 1-5, or saline injections on days 1-5.