Role of PKA/CREB/BDNF signaling in PM2.5-induced neurodevelopmental damage to the hippocampal neurons of rats

Liu, Jie; Liu, Benke; Yuan, Ping; Cheng, Li; Sun, Hong; Gui, Jianxiong; Pan, Yanan; Huang, Dishu; Chen, Hengsheng; Jiang, Li

doi:10.1016/j.ecoenv.2021.112005

Cited by 35 publications

(14 citation statements)

References 46 publications

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“…[ 25 ] As a result, we could reduce model preparation time dramatically while maintaining the viability of endothelial cells and microglia (Figures S1b and S3c , Supporting Information). The neuronal damage in our PMB models were comparable to other in vitro models, [ 26 ] but more severe than in vivo chronic models. [ 27 ] First, we attributed the lower sensitivity toward PM2.5‐driven neuroinflammation to the heterogeneous populations of glial cells playing either proinflammatory or anti‐inflammatory roles depending on brain regions, [ 6 , 16 , 17 ] while our models could separate PM2.5‐involving proinflammatory immune cells from other populations.…”

Section: Discussionsupporting

confidence: 76%

“…It should be noted that the optimized treatment concentration (10 µg mL −1 ) was in the range that was tested in other in vitro models. [ 26 ] From second treatment, one half of control or PM2.5 diluent was replaced every 3.5 days. For the control counterpart, the central chamber media was replaced to 100 µL of the differentiation media without PM2.5.…”

Section: Methodsmentioning

confidence: 99%

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An Air Particulate Pollutant Induces Neuroinflammation and Neurodegeneration in Human Brain Models

et al. 2021

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Fine particulate matter (PM2.5), a major component among air pollutants, highlights as a global health concern. Several epidemiological studies show the correlation between chronical PM2.5 exposure and incidents of neurological disorders including Alzheimer's disease. However, the mechanisms have not been well understood, partly due to the lack of model systems that reflect the physiologically relevant innate immunity in human brains. Here, PM2.5‐polluted human brain models (PMBs) are created in a 3D microfluidic platform reconstituting key aspects of human brain immunity under the PM2.5 exposure. PM2.5 penetration across a blood–brain barrier (BBB) model and accumulation in the brain tissue side of the model are first validated. Second, the PMB model shows that the BBB‐penetrating PM2.5 initiates astrogliosis, resulting in slight neuronal loss and microglial infiltration. Third, it is demonstrated that the infiltrating microglia obtain M1 phenotype induced by interleukin‐1β and interferon‐γ from neurons and reactive astrocytes under the PM2.5 exposure. Finally, it is observed that additional proinflammatory mediators and nitric oxide released from the M1 microglia exacerbate neuronal damages, such as synaptic impairment, phosphoric tau accumulation, and neuronal death. This study suggests that PM2.5 can be a potential environmental risk factor for dementia mediated by the detrimental neuroinflammation.

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Section: Discussionsupporting

confidence: 76%

Section: Methodsmentioning

confidence: 99%

An Air Particulate Pollutant Induces Neuroinflammation and Neurodegeneration in Human Brain Models

et al. 2021

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“…It may be a possible mechanism for the microbiome-gut-brain axis. PKA/CREB/BDNF signaling plays an important regulatory role in neurodevelopment, cognition and emotion 44 . Therefore, we assumed whether EE affected this pathway through microbiota.…”

Section: Discussionmentioning

confidence: 99%

Eleutheroside E supplementation prevents radiation-induced cognitive impairment and activates PKA signaling via gut microbiota

Song

Duan

et al. 2022

Commun Biol

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Radiation affects not only cognitive function but also gut microbiota. Eleutheroside E (EE), a principal active compound of Acanthopanax senticosus, has a certain protective effect on the nervous system. Here, we find a four-week EE supplementation to the 60Co-γ ray irradiated mice improves the cognition and spatial memory impairments along with the protection of hippocampal neurons, remodels the gut microbiota, especially changes of Lactobacillus and Helicobacter, and altered the microbial metabolites including neurotransmitters (GABA, NE, ACH, 5-HT) as well as their precursors. Furthermore, the fecal transplantation of EE donors verifies that EE alleviated cognition and spatial memory impairments, and activates the PKA/CREB/BDNF signaling via gut microbiota. Our findings provide insight into the mechanism of EE effect on the gut-brain axis and underpin a proposed therapeutic value of EE in cognitive and memory impairments induced by radiation.

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“…It is essential for maintaining and protecting the survival and growth of neurons ( 17 , 18 ). And the mouse model shows that the BDNF in the brain tissue can enter the blood through the blood-brain barrier, so it is speculated that the serum level can reflect the BDNF level in the brain ( 19 ). The results of this study showed that the serum BDNF content of the two groups of patients after treatment was higher than that before the treatment, and the serum BDNF content of the therapy group was higher than that of the control group.…”

Section: Discussionmentioning

confidence: 99%

Effects of Transient Electrical Acupuncture Stimulation Combined With Rehabilitation Training on Hemorheology, Neurological Function and BDNF in Patients With Cerebral Infarction

et al. 2022

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ObjectiveTo explore the effects of transient electric acupuncture stimulation combined with rehabilitation training on hemorheology, neurological function and brain-derived neurotrophic factor (BDNF) in patients with cerebral infarction (CI).MethodsA total of 90 patients with CI were admitted to our hospital from March 2019 to March 2021. According to the random number table method, 90 patients were divided into a control group (was treated with transient electrical acupuncture stimulation intervention treatment) and a therapy group (was treated with rehabilitation training on the basis of the control group), with 45 cases in each group. NIHSS score to detect neurological deficit; FMA score to detect motor function recovery; the clinical efficacy of the two groups of patients were compared; blood rheology analyzer to detect whole blood high shear viscosity, whole blood low shear viscosity, platelet aggregation rate and fibrinogen indicators; ELISA detects the content of BDNF in serum.ResultsThere was no significant difference in NIHSS score, FMA score, clinical efficacy, hemorheology index, and BDNF content between the two groups of patients before treatment (P > 0.05). After treatment, the NIHSS score, whole blood high shear visible, whole blood low shear visible, platelet aggregation rate and fibrinogen index of the two groups were lower than those before treatment, and the FMA score and BDNF content of the two groups were higher than those before treatment, and all the above indicators in the therapy group changed significantly compared with the control group (P < 0.05). After treatment, the clinical efficacy of the therapy group was better than that of the control group (P < 0.05).ConclusionThe combination of transient electrical acupuncture stimulation and rehabilitation training can inhibit the blood flow index of patients with CI, improve the nerve function, increase the content of BDNF in the patient's serum, and restore the patient's nerve function.

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Role of PKA/CREB/BDNF signaling in PM2.5-induced neurodevelopmental damage to the hippocampal neurons of rats

Cited by 35 publications

References 46 publications

An Air Particulate Pollutant Induces Neuroinflammation and Neurodegeneration in Human Brain Models

An Air Particulate Pollutant Induces Neuroinflammation and Neurodegeneration in Human Brain Models

Eleutheroside E supplementation prevents radiation-induced cognitive impairment and activates PKA signaling via gut microbiota

Effects of Transient Electrical Acupuncture Stimulation Combined With Rehabilitation Training on Hemorheology, Neurological Function and BDNF in Patients With Cerebral Infarction

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