Assessment of mouse cognitive and anxiety-like behaviors and hippocampal inflammation following a repeated and intermittent paradoxical sleep deprivation procedure.

It has been reported that more than one fourth of the world's population suffers from sleep problems. However, there is not a stable and reliable animal model to mimic the persistent and periodic features of sleep disorders, and correspondingly, the feasibility and effectiveness of repeated behavioral tests remains to be determined. In the present study, we repetitively, and intermittently, treated mice with 3days and 7days of paradoxical sleep deprivation (SD), using the modified multiple small-platforms-over-water method for 3 months. The behavioral results suggested that repeated open field and Y-maze tests are able to successfully detect anxiety-like behaviors and working memory dysfunction of the model mice. The Morris water maze test is not suitable for evaluating spatial learning ability following SD because the long-term utilization of the flower-pot method increases the familiarity of mice with the water environment. Moreover, neuroinflammation, microglial activation and neuronal apoptosis were observed in the hippocampus of model mice even recovery for 3 weeks later. This animal model and corresponding behavioral evaluation method will help to explore the pathogenesis and therapeutic strategies of chronic sleep disorders.

Behavioral assessment of cognitive function using a translational neonatal piglet model.

Pigs are used in myriad research disciplines related to human health, but no studies have employed the piglet to directly assess cognitive function during the neonatal period. Our objective was to develop a behavioral assay for neonatal piglets to assess learning and memory. At 2-wk of age, piglets were trained to locate a milk reward in an 8-arm radial maze using colored intra-maze cues (acquisition phase, 60-s trials with 8 trials per d for 4d). Cue colors were then reversed and pigs re-tested to assess learning and working memory (reversal phase). Piglets quickly learned the simple associative acquisition task, and proficiency greatly improved throughout reversal testing. To further assess the behavioral assay, piglets received an i.p. injection of saline or polyinosinic:polycytidylic acid (poly I:C; 5mg/kg body weight) immediately preceding reversal testing. Poly I:C-treated piglets exhibited acute sickness behaviors, but observationally, were asymptomatic 12-h post-injection. Pro-inflammatory cytokine mRNA expression was elevated 4-h post-injection in both peripheral and central compartments, and plasma cytokine protein levels were concurrently elevated. Specifically, poly I:C elicited the largest increases in interleukin (IL)-1ß mRNA in the liver, spleen, and hippocampus. At 24-, 48-, and 72-h post-injection (i.e., after acute sickness), poly I:C-treated piglets committed more incorrect arm entries, required more time to complete the reversal task, and moved a greater distance in the maze compared with control piglets. Collectively, these data demonstrate that neonatal piglets are capable of being trained in traditional learning and memory tests, and peripheral immune activation elicits alterations in cognitive processing in the neonate.