脑部炎症极大地破坏记忆检索网络

Brain inflammation can rapidly disrupt our ability to retrieve ¹ complex memories of similar but distinct experiences, according to UC Irvine neuroscientists Jennifer Czerniawski and John Guzowski. Their study -- which appears today in The Journal of Neuroscience -- specifically identifies how immune system signaling molecules ², called cytokines, impair ³ communication among neurons in the hippocampus, an area of the brain critical for discrimination memory. The findings offer insight into why cognitive ⁴ deficits ⁵ occurs in people undergoing chemotherapy and those with autoimmune or neurodegenerative diseases., ,Moreover, since cytokines are elevated in the brain in each of these conditions, the work suggests potential therapeutic ⁶ targets to alleviate ⁷ memory problems in these patients., ,"Our research provides the first link among immune system activation ⁸, altered neural ⁹ circuit function and impaired ¹⁰ discrimination memory," said Guzowski, the James L. McGaugh Chair in the Neurobiology of Learning & Memory. "The implications may be beneficial for those who have chronic ¹¹ diseases, such as multiple sclerosis, in which memory loss occurs and even for cancer patients.", ,What he found interesting is that increased cytokine levels in the hippocampus only affected ¹² complex discrimination memory, the type that lets us differentiate ¹³ among generally similar experiences -- what we did at work or ate at dinner, for example. A simpler form of memory processed by the hippocampus -- which would be akin ¹⁴ to remembering where you work -- was not altered by brain inflammation., ,In the study, Czerniawski, a UCI postdoctoral scholar, exposed rats to two similar but discernable environments over several days. They received a mild foot shock daily in one, making them apprehensive ¹⁵ about entering that specific site. Once the rodents ¹⁶ showed that they had learned the difference between the two environments, some were given a low dose of a bacterial ¹⁷ agent to induce a neuroinflammatory response, leading to cytokine release in the brain. Those animals were then no longer able to distinguish between the two environments., ,Afterward ¹⁸, the researchers explored the activity patterns of neurons -- the primary cell type for information processing -- in the rats' hippocampi using a gene-based cellular ¹⁹ imaging method developed in the Guzowski lab. In the rodents that received the bacterial agent (and exhibited memory deterioration), the networks of neurons activated ²⁰ in the two environments were very similar, unlike those in the animals not given the agent (whose memories remained strong). This finding suggests that cytokines impaired recall by disrupting the function of these specific neuron circuits in the hippocampus., ,"The cytokines caused the neural network to react as if no learning had taken place," said Guzowski, associate professor of neurobiology & behavior. "The neural circuit activity was back to the pattern seen before learning."