Anti-inflammatory and antioxidant effects of muscarinic acetylcholine receptor (mAChR) activation in the rat hippocampus

Abstract

Recently we found that acute treatment with Oxotremorine (Oxo), a non-selective mAChRs agonist, up-regulates heat shock proteins and activates their transcription factor heat shock factor 1 in the rat hippocampus. Here we aimed to investigate: a) if acute treatment with Oxo may regulate pro-inflammatory or anti-inflammatory cytokines and oxidative stress in the rat hippocampus; b) if chronic restraint stress (CRS) induces inflammatory or oxidative alterations in the hippocampus and whether such alterations may be affected by chronic treatment with Oxo. In the acute experiment, rats were injected with single dose of Oxo (0.4 mg/kg) and sacrificed at 24 h, 48 h and 72 h. In the CRS experiment, the rats were exposed for 21 days to the CRS and then were treated with Oxo (0.2 mg/kg) for further 10 days. The acute Oxo treatment showed an ability to significantly reduce reactive oxygen species (ROS), singlet oxygen (1O2), pro-inflammatory cytokines levels (IL-1β and IL-6) and phosphorylated NF-κB-p65. Acute Oxo treatment also increased superoxide dismutase (SOD)-2 protein levels and stimulated SOD activity. No differences were detected in the anti-inflammatory cytokine levels, including IL-10 and TGF-β1. In the group of rats exposed to the CRS were found increased hippocampal IL-1β and IL-6 levels, together with a reduction of SOD activity level. These changes produced by CRS were counteracted by chronic Oxo treatment. In contrast, the upregulation of ROS and 1O2 levels in the CRS group was not counteracted by chronic Oxo treatment. The results revealed a hippocampal anti-inflammatory and antioxidant effect of Oxo treatment in both basal conditions and anti-inflammatory in the CRS rat model.

Muscarinic-Dependent miR-182 and QR2 Expression Regulation in the Anterior Insula Enables Novel Taste Learning

“…However, the mechanisms upstream of QR2 expression reduction and how this reduction allows the 5 formation of incidental taste memory are unknown. Furthermore, mAChR activation not only leads to QR2 reduced expression but is also known to affect reactive oxygen species (ROS) clearance (Frinchi et al, 2019). Since QR2 activity can directly influence cellular ROS levels and redox state (Cassagnes et al, 2018), it is unclear whether some of the anti-inflammatory effect of mAChR activation is mediated by QR2 suppression.…”

Impact of Key Nicotinic AChR Subunits on Post-Stroke Pneumococcal Pneumonia

“…In the CNS, mAChRs have been associated with the cholinergic anti-inflammatory pathway. An anti-inflammatory and anti-oxidant effect in the hippocampus of rats was demonstrated by stimulation of mAChRs with the agonist oxotremorine [ 41 ]. Furthermore, adrenocorticotropin treatment of rats diminished hemorrhagic shock by activation of the cholinergic anti-inflammatory pathway via mAChRs in the CNS [ 42 ].…”

The dialog between neurons and microglia in Alzheimer's disease: The neurotransmitters view

“…The most severely affected neuron population in AD is of the cholinergic neurons of the nucleus basalis of Meynert (Bartus et al., 1982; Coyle et al., 1983; Mufson et al., 2002; Winkler et al., 1998; Wu et al., 2005). Their neurotransmitter, ACh, is a neuromodulator in the brain with many activities, such as alteration of neuronal excitability, neurogenesis, synaptic plasticity, and transmission (Frinchi et al., 2019; Picciotto et al., 2012). ACh has also been shown to play a central role in memory and attention (Bartus et al., 1982; Mufson et al., 2002; Picciotto et al., 2012; Soreq, 2001) and to exert anti‐inflammatory and neuroprotective effects (Frinchi et al., 2019; Kaczmarczyk et al., 2018; Li et al., 2019).…”

“…Their neurotransmitter, ACh, is a neuromodulator in the brain with many activities, such as alteration of neuronal excitability, neurogenesis, synaptic plasticity, and transmission (Frinchi et al., 2019; Picciotto et al., 2012). ACh has also been shown to play a central role in memory and attention (Bartus et al., 1982; Mufson et al., 2002; Picciotto et al., 2012; Soreq, 2001) and to exert anti‐inflammatory and neuroprotective effects (Frinchi et al., 2019; Kaczmarczyk et al., 2018; Li et al., 2019). The cholinergic deficiency created in AD, because of the loss of cholinergic neurons and ACh, contributes greatly to the cognitive deterioration that characterizes the disease (Bartus et al., 1982; Mufson et al., 2002; Soreq, 2001).…”