Limits...
Sepsis-induced selective parvalbumin interneuron phenotype loss and cognitive impairments may be mediated by NADPH oxidase 2 activation in mice.

Ji MH, Qiu LL, Tang H, Ju LS, Sun XR, Zhang H, Jia M, Zuo ZY, Shen JC, Yang JJ - J Neuroinflammation (2015)

Bottom Line: For the interventional study, the animals were chronically treated with a nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor, apocynin, at 5 mg/kg.Primary hippocampal neuronal cultures were used to investigate the mechanisms underlying the dysfunction of PV interneurons.Notably, these abnormalities could be rescued by apocynin treatment.

View Article: PubMed Central - PubMed

Affiliation: Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Nanjing, 210002, China. jimuhuo2009@sina.com.

ABSTRACT

Background: Sepsis-associated encephalopathy (SAE) is a diffuse brain dysfunction caused by many pathological events, including neuroinflammation and oxidative stress damage. Increasing evidence suggests that parvalbumin (PV) interneurons play a key role in the cognitive process, whereas the dysfunction of these interneurons has been implicated in a number of major psychiatric disorders. Here, we aimed to investigate whether enhanced inflammation and oxidative stress-mediated PV interneuron phenotype loss plays a role in sepsis-induced cognitive impairments.

Methods: Male C57BL/6 mice were subjected to cecal ligation and puncture or sham operation. For the interventional study, the animals were chronically treated with a nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor, apocynin, at 5 mg/kg. The mice were euthanized at the indicated time points, and the brain tissues were harvested for determination of the PV, membrane subunit of NADPH oxidase gp91(phox), and markers of oxidative stress (4-hydroxynonenal and malondialdehyde) and inflammation (tumor necrosis factor alpha (TNF-α), interleukin (IL)-1β, IL-6, and IL-10). A separate cohort of animals was used to evaluate the behavioral alterations by the open field and fear conditioning tests. Primary hippocampal neuronal cultures were used to investigate the mechanisms underlying the dysfunction of PV interneurons.

Results: Sepsis resulted in cognitive impairments, which was accompanied by selective phenotype loss of PV interneurons and increased gp91(phox), 4-hydroxynonenal, malondialdehyde, IL-1β, and IL-6 expressions. Notably, these abnormalities could be rescued by apocynin treatment.

Conclusion: Selective phenotype loss of PV interneurons, as a result of NADPH oxidase 2 (Nox2) activation, might partly contribute to cognitive impairments in a mouse model of SAE.

No MeSH data available.


Related in: MedlinePlus

LPS exposure decreased the number of excitatory synapses in the PV interneurons. a Representative images of PV (green) and PSD-95 (red) in the primary hippocampal neuronal cultures. b Apocynin treatment reversed LPS exposure-induced decrease in the number of PSD95 puncta in the PV interneurons. Data are presented as mean ± SEM (n = 6). #p < 0.05 vs the control groups; *p < 0.05 vs the LPS + vehicle group. Scale bar = 20 μm
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
getmorefigures.php?uid=PMC4587802&req=5

Fig10: LPS exposure decreased the number of excitatory synapses in the PV interneurons. a Representative images of PV (green) and PSD-95 (red) in the primary hippocampal neuronal cultures. b Apocynin treatment reversed LPS exposure-induced decrease in the number of PSD95 puncta in the PV interneurons. Data are presented as mean ± SEM (n = 6). #p < 0.05 vs the control groups; *p < 0.05 vs the LPS + vehicle group. Scale bar = 20 μm

Mentions: To investigate the mechanisms underlying sepsis-induced PV interneuron dysfunction, we examined PSD-95, a major scaffolding protein located at excitatory synapses. The in vitro study revealed that LPS led to significantly fewer PSD-95 puncta numbers when compared with the LPS + vehicle group. Notably, apocynin treatment significantly increased PSD-95 puncta number after LPS exposure [one-way ANOVA; F (3, 28) = 7.863, p = 0.01; Fig. 10a, b].Fig. 10


Sepsis-induced selective parvalbumin interneuron phenotype loss and cognitive impairments may be mediated by NADPH oxidase 2 activation in mice.

Ji MH, Qiu LL, Tang H, Ju LS, Sun XR, Zhang H, Jia M, Zuo ZY, Shen JC, Yang JJ - J Neuroinflammation (2015)

LPS exposure decreased the number of excitatory synapses in the PV interneurons. a Representative images of PV (green) and PSD-95 (red) in the primary hippocampal neuronal cultures. b Apocynin treatment reversed LPS exposure-induced decrease in the number of PSD95 puncta in the PV interneurons. Data are presented as mean ± SEM (n = 6). #p < 0.05 vs the control groups; *p < 0.05 vs the LPS + vehicle group. Scale bar = 20 μm
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4587802&req=5

Fig10: LPS exposure decreased the number of excitatory synapses in the PV interneurons. a Representative images of PV (green) and PSD-95 (red) in the primary hippocampal neuronal cultures. b Apocynin treatment reversed LPS exposure-induced decrease in the number of PSD95 puncta in the PV interneurons. Data are presented as mean ± SEM (n = 6). #p < 0.05 vs the control groups; *p < 0.05 vs the LPS + vehicle group. Scale bar = 20 μm
Mentions: To investigate the mechanisms underlying sepsis-induced PV interneuron dysfunction, we examined PSD-95, a major scaffolding protein located at excitatory synapses. The in vitro study revealed that LPS led to significantly fewer PSD-95 puncta numbers when compared with the LPS + vehicle group. Notably, apocynin treatment significantly increased PSD-95 puncta number after LPS exposure [one-way ANOVA; F (3, 28) = 7.863, p = 0.01; Fig. 10a, b].Fig. 10

Bottom Line: For the interventional study, the animals were chronically treated with a nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor, apocynin, at 5 mg/kg.Primary hippocampal neuronal cultures were used to investigate the mechanisms underlying the dysfunction of PV interneurons.Notably, these abnormalities could be rescued by apocynin treatment.

View Article: PubMed Central - PubMed

Affiliation: Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Nanjing, 210002, China. jimuhuo2009@sina.com.

ABSTRACT

Background: Sepsis-associated encephalopathy (SAE) is a diffuse brain dysfunction caused by many pathological events, including neuroinflammation and oxidative stress damage. Increasing evidence suggests that parvalbumin (PV) interneurons play a key role in the cognitive process, whereas the dysfunction of these interneurons has been implicated in a number of major psychiatric disorders. Here, we aimed to investigate whether enhanced inflammation and oxidative stress-mediated PV interneuron phenotype loss plays a role in sepsis-induced cognitive impairments.

Methods: Male C57BL/6 mice were subjected to cecal ligation and puncture or sham operation. For the interventional study, the animals were chronically treated with a nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor, apocynin, at 5 mg/kg. The mice were euthanized at the indicated time points, and the brain tissues were harvested for determination of the PV, membrane subunit of NADPH oxidase gp91(phox), and markers of oxidative stress (4-hydroxynonenal and malondialdehyde) and inflammation (tumor necrosis factor alpha (TNF-α), interleukin (IL)-1β, IL-6, and IL-10). A separate cohort of animals was used to evaluate the behavioral alterations by the open field and fear conditioning tests. Primary hippocampal neuronal cultures were used to investigate the mechanisms underlying the dysfunction of PV interneurons.

Results: Sepsis resulted in cognitive impairments, which was accompanied by selective phenotype loss of PV interneurons and increased gp91(phox), 4-hydroxynonenal, malondialdehyde, IL-1β, and IL-6 expressions. Notably, these abnormalities could be rescued by apocynin treatment.

Conclusion: Selective phenotype loss of PV interneurons, as a result of NADPH oxidase 2 (Nox2) activation, might partly contribute to cognitive impairments in a mouse model of SAE.

No MeSH data available.


Related in: MedlinePlus