Hippocampal AMPARs involve the central sensitization of rats with irritable bowel syndrome

Abstract

ObjectiveThe roles of hippocampal AMPARs were investigated in irritable bowel syndrome (IBS)‐like rats to clarify the central sensitization mechanisms.Methods IBS model was induced by neonatal maternal separation. The effects of AMPARs on visceral hypersensitivity were examined by the responses of abdominal muscle to colorectal distension after the bilateral intrahippocampal injections of CNQX (an AMPAR inhibitor). The expressions of hippocampal AMPARs (GluR1 and GluR2) were determined by Western blot.ResultsThe IBS‐like rats showed visceral hypersensitivity when compared with controls. Bilateral intrahippocampal injections of CNQX alleviated the visceral pain in IBS‐like rats. The maximal effect appeared at the time point of 30 min, and the duration lasted for 90 min after CNQX application, under 40 and 60 mmHg CRD. The expressions of hippocampal GluR2 significantly increased in IBS‐like rats when compared with controls (p < .05). However, the levels of hippocampal GluR1 had no significant differences in rats. Hippocampal LTP induced by HFS was significantly enhanced when compared with controls (p < .05). The expressions of GluR2 significantly increased in the control and IBS‐like rats after 60 min LTP of recordings (p < .05), but not GluR1.ConclusionNeonatal maternal separation enhances the expression of GluR2 and facilitates the LTP in the hippocampus, which could lead to the formation of visceral hypersensitivity when grown up.

Antioxidant Capacity and Behavioral Relevance of a Polyphenolic Extract of Chrysanthellum americanum in a Rat Model of Irritable Bowel Syndrome

“…Previous studies showed that failure of stress-coping mechanisms in some IBS subsets patients could lead to inadequate neuroendocrine autonomic responses along the HPA, such as altered cortisol levels and increased vagal activation [8, 63, 64]. In this way, their sensory information processing is impaired by the overload of the emotional circuitry, as shown by some sparse studies on functional magnetic resonance imaging in IBS subjects [65] or immunochemistry in animal models [66]. Even more interesting, persistent stress in animal models is shown to morphologically alter hippocampal circuitry and suppress neurogenesis [8], while two recent studies of Mayer and colleagues demonstrate decreased gray matter density in prefrontal cortex, posterior parietal cortex, pregenual anterior cingulate cortex, and similar trends in the posterior insula/secondary somatosensory cortex, (para)hippocampus, regions involved in cognitive functions among others [67].…”

Maternal separation in rodents: a journey from gut to brain and nutritional perspectives

“…MS induces both functional and structural changes in several brain regions including the PFC, hippocampus, amygdala and nucleus accumbens (150,158–163) . More specifically, impaired synaptic long-term potentiation, dendritic atrophy as well as reduced dendritic spine density have been reported in the medial PFC and hippocampus of adolescent and adult MS rats (63,68,97,104,116,140,153,158,164–171) . By contrast, MS induces dendritic hypertrophy in the amygdala (57) .…”

“…The gabaergic system plays a role in CRF synthesis inhibition in the central amygdala, allowing a buffering of the noradrenergic response to stress. In addition, MS impairs glutamatergic (140–142) , serotonergic (48,61,83,143–147) , dopaminergic (64,145,148–153) , opioidergic (152,154) and endocannabinoidergic (66) transmission. In the central nervous system, serotonin is involved in neuronal development (155) , emotionality and also pain modulation (156,157) .…”

Glutamatergic Signaling Along The Microbiota-Gut-Brain Axis

“…Recently, in a rat model of maternal separation-induced IBS associated with alterations of the microbiota homeostasis, bilateral hippocampal injection of the AMPA receptor antagonist, CNQX, reduced visceral pain perception to colorectal distension. In addition, GluA2 receptor levels significantly increased in the hippocampus of IBS-like rats, with respect to controls, both in normal conditions and after high electrical field induced LTP-responses, suggesting a possible involvement of GluA2 subunits in central mechanisms of chronic visceral pain control [195]. Persistence of pain perception in IBS, depends upon changes in afferent neurons and CNS pain processing pathways, leading to chronic visceral hypersensitivity [75].…”