Increased GABAergic projections in the paraventricular nucleus regulate colonic hypersensitivity via oxytocin in a rat model of irritable bowel syndrome

Abstract

Irritable bowel syndrome (IBS) is characterized by gastrointestinal dysmotility and visceral hyperalgesia, and the impaired brain-gut axis is accepted as a crucial cause for the onset of IBS. The objective of this study is to investigate the effects of the adaptive changes in the central neural system induced by stress on IBSlike syndromes in rats. Long-term water avoidance stress (WAS) was used to prepare IBS animals. The changes in neuronal excitation and GABA expression were shown by immunohistochemistry. The mRNA and protein expressions of neurotransmitters were detected with Quantitative reverse-transcription PCR (qRT-PCR) and Enzyme-linked immunosorbent assay (ELISA). The intestinal transit time, fecal moisture content, and abdominal withdrawal reflex scores of rats were recorded to monitor intestinal motility and visceral hyperalgesia. In the WAS-treated rats with enhanced intestinal motility and visceral hypersensitivity, more GABAergic projections were found in the paraventricular nucleus (PVN) of the hypothalamus, which inhibited the firing rate of neurons and decreased the expression of oxytocin. Exogenous oxytocin improved gut motility and decreased AWR scores. The inhibition of oxytocin by the adaptive GABAergic projection in the PVN might be an important mediator of IBS, which indicates a potential novel therapeutic target.

Inhibition of GABAergic neurons in the paraventricular nucleus of the hypothalamus precipitates visceral pain induced by pancreatic cancer in mice

“…Arginine vasopressin (AVP)-positive neurons in the PVN project to the solitary tract nucleus; therefore, activating AVP-positive neurons can protect intestinal mucosa through the vagus nerve and relieve visceral pain ( 14 ). Additionally, oxytocin-positive neurons exist in the PVN and have significant analgesic effects ( 17 - 19 ); thus, activating oxytocin-positive neurons can also alleviate visceral pain ( 20 , 21 ). Therefore, we believe that future research should focus on studying the specific roles of different types of PVN neurons in visceral pain and identifying protective versus harmful neurons for more targeted modulation and better relief from visceral pain.…”

Human clostridia improve visceral hypersensitivity in stressed mice through upregulation of 5-HT4

“…WAS can lead to visceral hypersensitivity and depressive symptoms and is a reliable model that has been widely used as an animal model of IBS or depression and anxiety 30,31 . Li et al 32 found increased fecal water content in WAS mice compared to the normal group, and Bradesi et al 33 found a signi cant increase in EMG amplitude in WAS mice compared to the normal group in electromyographic tests. In the present study, a decrease in the rate of body weight gain was observed in the WAS mice compared to the normal group, which may be due to a decrease in the amount of food eaten by the stressed mice; we also observed a decrease in activity and food intake in the WAS mice during the experiment.…”

Role of GABA pathway in motor and non-motor symptoms in Parkinson's disease: a bidirectional circuit

“…K + -Cl mainly mediates the polarity of GABA neurons to inhibitory functions − co-transporter (KCC2) [ 27 ]. Oxytocin plays a critical role in the transition of GABAergic neurons to inhibitory processes through modulation of KCC2 [ 28 ]. In the absence of oxytocin, the activity of KCC2 is reduced with an increase in hyper-excitability state and related disorders like epilepsy and neurodevelopmental disorders [ 28 ].…”

“…Oxytocin plays a critical role in the transition of GABAergic neurons to inhibitory processes through modulation of KCC2 [ 28 ]. In the absence of oxytocin, the activity of KCC2 is reduced with an increase in hyper-excitability state and related disorders like epilepsy and neurodevelopmental disorders [ 28 ]. Besides, expressions of GABA A receptors are regulated by allopregnanolone steroid, which exerts positive and negative impacts in acute and chronic effect correspondingly on the expression of GABA A receptors and the progression of dementia [ 29 ].…”