Reduced inhibition underlies early life LPS exposure induced-cognitive impairment: Prevention by environmental enrichment

NLRP3-Mediated Piezo1 Upregulation in ACC Inhibitory Parvalbumin-Expressing Interneurons Is Involved in Pain Processing after Peripheral Nerve Injury

“…Under physiological conditions, the microglial morphology is ramified; in case of injury or neuroinflammation, the microglia change to take an amoeba-like morphology conferring an increased phagocytosis ability [ 77 , 81 ]. Microglial activation and PV-IN dysfunction in the hippocampus and medial prefrontal cortex (mPFC) were achieved in the systemic inflammatory model prepared using intraperitoneal lipopolysaccharide (LPS) injection [ 82 , 83 , 84 ]. Activated microglia may promote central disinhibition by selectively phagocytosing inhibitory synaptic terminals [ 84 ] or displacing inhibitory axosomatic presynaptic terminals from cortical neurons [ 85 ]; moreover, blocking microglial activation alleviates PV-IN dysfunction and behavioral changes caused by inflammation or brain injury [ 82 , 83 , 86 ].…”

Delayed effects of neonatal immune activation on brain neurochemistry and hypothalamic–pituitary–adrenal axis functioning

“…NIA on PND3–PND13 reduces GABAergic neurotransmission in the brain. In response to the administration of LPS, the levels of the neurotransmitter GABA and of its receptor GABA A decline in the hippocampus and prefrontal cortex in adolescent and adult rodents (Kubesova et al, 2015; Liang et al, 2019; Wu et al, 2021). In addition, in adolescent animals on PND42, there is downregulation of vesicular GABA transporter (vGAT) and of the main enzyme for GABA synthesis: glutamate decarboxylase (GAD67) (Wu et al, 2021), but in adults, concentrations of these molecules do not differ from those in a control (Liang et al, 2019).…”

“…In response to the administration of LPS, the levels of the neurotransmitter GABA and of its receptor GABA A decline in the hippocampus and prefrontal cortex in adolescent and adult rodents (Kubesova et al, 2015; Liang et al, 2019; Wu et al, 2021). In addition, in adolescent animals on PND42, there is downregulation of vesicular GABA transporter (vGAT) and of the main enzyme for GABA synthesis: glutamate decarboxylase (GAD67) (Wu et al, 2021), but in adults, concentrations of these molecules do not differ from those in a control (Liang et al, 2019). In this context, the amounts of glutamate and the vesicular glutamate transporter (vGLUT1) (its main transporter) do not change in adolescent mice (Wu et al, 2021) but increase in adult rodents (Gomez et al, 2021; Kubesova et al, 2015).…”

“…In addition, in adolescent animals on PND42, there is downregulation of vesicular GABA transporter (vGAT) and of the main enzyme for GABA synthesis: glutamate decarboxylase (GAD67) (Wu et al, 2021), but in adults, concentrations of these molecules do not differ from those in a control (Liang et al, 2019). In this context, the amounts of glutamate and the vesicular glutamate transporter (vGLUT1) (its main transporter) do not change in adolescent mice (Wu et al, 2021) but increase in adult rodents (Gomez et al, 2021; Kubesova et al, 2015). On Day 14 after the administration of LPS in adult mice, a similar shift in the balance towards glutamatergic activity is observed in CA1 pyramidal neurons of the hippocampus: The amount of glutamate goes up, whereas the activity of presynaptic GABA B receptor, which regulates the reuptake of GABA from the synaptic cleft, declines (Gomez et al, 2021).…”

“…Thus, hyperactivation of the glutamatergic system can be caused either by stronger glutamatergic signalling or by suppression of the inhibitory action of GABAergic neurons. It has been reported that a decrease in the activity of the GABAergic system in adolescent mice induces working‐memory impairment (Wu et al, 2021) and in adult mice gives rise to depressive but not anxious behaviour (Liang et al, 2019; Wu et al, 2021).…”