vasoactive-intestinal-peptide and Cognitive-Dysfunction

Cognitive dysfunction caused by sepsis-associated encephalopathy (SAE) is still poorly understood. It is reported that vasoactive intestinal peptide (VIP) exerts its anti-inflammatory effects in multiple diseases, while its biological function in SAE remains unclear. We aimed to figure out whether VIP has influence on sepsis-induced neuroinflammation and cognitive dysfunction. To induce sepsis, rats were subjected to cecal ligation and puncture (CLP) operation. Morris water maze test and fear conditioning test were conducted to reveal cognitive dysfunctions. TUNEL assay was performed to evaluate apoptosis. We found out that the expression of VIP was downregulated in the hippocampus of septic rats. VIP was verified to attenuate sepsis-induced memory impairment following CLP. Additionally, we examined apoptosis and inflammation in rats' hippocampus. It is worth noting that VIP inhibited the apoptosis in the hippocampus and reduced the productions of proinflammatory cytokines TNF-α, IL-6 and IL-1β. Furthermore, our data confirmed that VIP was involved in regulating the TLR-4/NF-κB signaling. In conclusion, VIP inhibited neuroinflammation and cognitive impairment in hippocampus of septic rats through the TLR-4/NF-κB signaling pathway.

Topics: Animals; Cognitive Dysfunction; Hippocampus; NF-kappa B; Rats; Sepsis; Sepsis-Associated Encephalopathy; Signal Transduction; Toll-Like Receptor 4; Vasoactive Intestinal Peptide

Caffeine is a common stimulant widely existed in food and has stimulatory effects on the central nervous system, shift-work individuals often rely on caffeine to maintain attention and keep awake. Although sleep deprivation (SD) is widely considered as an independent risk factor for cognition retardations, however, little is well understood about the synergistic role of caffeine dosage and SD for cognitive performance. This research intended to investigate the underlying molecular mechanism of varying caffeine doses on cognitive function after sleep deprivation. The results revealed that SD attenuated the cognitive dysfunction, associated with ultrastructure damage and pyramidal neuron loss in the hippocampus, decreased in the level of VIP and AVP. SD also significantly accelerated the neuropeptide-associated apoptosis in the hippocampus, which may modulate via the cAMP-PKA-CREB signal path axis and activation of the downstream apoptosis genes. Additionally, the data indicated that low-dose caffeine (LC) contributed to cognitive enhancement, and high-dose caffeine (HC) aggravated cognitive impairment by modulating hippocampal neuronal apoptosis. Our studies suggest that caffeine, particularly in high dosage, may be a potential factor to influence the neurocognitive outcome caused by sleep loss, and the appropriate amount of caffeine ingested after sleep deprivation deserves serious consideration.

Topics: Animals; Apoptosis; Arginine Vasopressin; Caffeine; Central Nervous System Stimulants; Cognition; Cognitive Dysfunction; Disease Models, Animal; Dose-Response Relationship, Drug; Hippocampus; Humans; Male; Mitochondria; Motor Activity; Nootropic Agents; Pyramidal Cells; Rats; Rats, Sprague-Dawley; Signal Transduction; Sleep Deprivation; Spatial Learning; Vasoactive Intestinal Peptide