Acute neuroimmune stimulation impairs verbal memory in adults: A PET brain imaging study.
Acute neuroimmune stimulation impairs verbal memory in adults: A PET brain imaging study.
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DOI：
10.1016/j.bbi.2020.09.027
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发表时间：
2021-01
期刊：
影响因子：
--
通讯作者：
Pietrzak RH
中科院分区：
文献类型：
--
作者：
Woodcock EA;Hillmer AT;Sandiego CM;Maruff P;Carson RE;Cosgrove KP;Pietrzak RH
Psychiatric and neurologic disorders are often characterized by both neuroinflammation and cognitive dysfunction. To date, however, the relationship between neuroinflammation and cognitive dysfunction remains understudied in humans. Preclinical research indicates that experimental induction of neuroinflammation reliably impairs memory processes. In this paradigm development study, we translated those robust preclinical findings to humans using positron emission tomography (PET) imaging with [11C]PBR28, a marker of microglia, and lipopolysaccharide (LPS), a potent neuroimmune stimulus. In a sample of 18 healthy adults, we confirmed our previous findings that LPS administration increased whole-brain [11C]PBR28 availability by 3150%, demonstrating a robust neuroimmune response (Cohen’s ds>1.6). We now show that LPS specifically impaired verbal learning and recall, hippocampal memory processes, by 11% and 22%, respectively (Cohen’s ds>0.9), but did not alter attention, motor, or executive processes. The LPS-induced increase in [11C]PBR28 binding was correlated with significantly greater decrements in verbal learning performance in the hippocampus (r=−0.52, p=.028), putamen (r=−0.50, p=.04), and thalamus (r=−0.55, p=.02). This experimental paradigm may be useful in investigating mechanistic relationships between neuroinflammatory signaling and cognitive dysfunction in psychiatric and neurologic disorders. It may also provide a direct approach to evaluate medications designed to rescue cognitive deficits associated with neuroinflammatory dysfunction.
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