Mohammed A K, Magnusson O, Maehlen J, Fonnum F, Norrby E, Schultzberg M, Kristensson K
Department of Geriatric Medicine, Karolinska Institute, Huddinge Hospital, Sweden.
Neuroscience. 1990;35(2):355-63. doi: 10.1016/0306-4522(90)90089-m.
Dysfunction of subcortical serotoninergic neurons has been implicated in some behaviour disturbances. The serotoninergic neurons in the dorsal and median raphe project widely in the brain. They innervate the olfactory bulbs and can be targets for exogenous agents attacking the olfactory epithelium and bulbs. We report here an injury to the serotoninergic neurons after intranasal infection in 12-day-old rats with a temperature-sensitive mutant of vesicular stomatitis virus. The brain infection was focal and transient. Viral antigens could no longer be detected 13-15 days after infection. In spite of this the animals, as adults, had a severe serotonin depletion in the cerebral cortex and hippocampus, and showed abnormal locomotor and explorative behaviour as well as learning deficits. The neocortex was histologically intact and parameters related to other neurotransmitters such as dopamine, noradrenaline, GABA and acetylcholine showed no marked changes. A relatively selective damage to serotoninergic nuclei as a result of virus neuroinvasion through a natural portal of entry, may constitute a new pathogenetic mechanism for cortical dysfunction and behavioural deficits.
皮层下5-羟色胺能神经元功能障碍与某些行为紊乱有关。中缝背核和中缝正中核中的5-羟色胺能神经元在大脑中广泛投射。它们支配嗅球，并且可能成为攻击嗅上皮和嗅球的外源性物质的靶点。我们在此报告，用对温度敏感的水疱性口炎病毒突变体对12日龄大鼠进行鼻内感染后，5-羟色胺能神经元受到损伤。脑部感染是局灶性且短暂的。感染后13 - 15天就再也检测不到病毒抗原了。尽管如此，这些动物成年后，大脑皮层和海马体中的5-羟色胺严重耗竭，并表现出异常的运动和探索行为以及学习缺陷。新皮层在组织学上是完整的，与其他神经递质如多巴胺、去甲肾上腺素、γ-氨基丁酸和乙酰胆碱相关的参数没有明显变化。病毒通过自然进入途径进行神经侵袭导致5-羟色胺能核团相对选择性损伤，可能构成皮层功能障碍和行为缺陷的一种新的发病机制。
