Fig. 4

Stress gateway reflex. Hostile environment induced by a specific cage with water and a free rotation wheel causes chronic stress associated with sleep disorder. In a mouse with adoptive-transfer EAE, this chronic stress stimulates noradrenergic neurons in the PVN (1), which then project to bilateral specific vessels surrounded by the third ventricle (3V), dentate gyrus (DG) and thalamus (TH) (2) to upregulate chemokines including CCL5 and recruit pathogenic CD4+ T cells plus MHC class II+ monocytes. The resulted microinflammation activates a neural pathway involving the DMH/AHP and DMX via ATP production (3). Hyperactivation of the vagus pathway particularly distributed the upper gastrointestinal (GI) tract causes a severe damage in the upper GI tract followed by a heart failure with sudden death (5). Abbreviations: AHP, anterior hypothalamic area; EAE, experimental autoimmune encephalomyelitis; PVN, paraventricular nucleus of the hypothalamus; DMH, dorsomedial nucleus of the hypothalamus; DMX, dorsal motor nucleus of the vagus nerve; NTS, nucleus tractus solitarii; 4V, fourth ventricle