Differential behavioral and glial responses induced by dopaminergic mechanisms in the iNOS knockout mice

Issy, Ana Carolina; Nascimento, Glauce Crivelaro do; Abreu, Gabriel H Dias de; Tristão, Fabrine Sales Massafera; Del‐Bel, Elaine; Duarte, Terence; Bortolanza, Mariza

doi:10.1016/j.bbr.2018.05.002

Cited by 5 publications

(7 citation statements)

References 71 publications

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“…iNOS is an important inflammatory signal molecule. The increase in iNOS also indicates that microglia are activated by inflammatory stimulation (Issy et al, 2018). Therefore, AD animal models have different degrees of inflammatory activation, and NLRP3 inflammatory bodies may mediate this inflammatory reaction.…”

Section: Discussionmentioning

confidence: 99%

Enhanced Autolysosomal Function Ameliorates the Inflammatory Response Mediated by the NLRP3 Inflammasome in Alzheimer’s Disease

Zhou

Deng

Zhao

et al. 2021

Front. Aging Neurosci.

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The pathogenesis of Alzheimer’s disease (AD) involves activation of many NLRP3 inflammatory bodies, which may be related to amyloid β peptide and aggregation of misfolded proteins. Autophagy is an important regulator of inflammatory bodies. However, autophagy shows dynamic changes in the development of AD, and its role in inflammation remains controversial. In this study, the key link between autophagic disorders and the NLRP3 inflammasome in AD was investigated. APP/PS1 double transgenic mice and C57 mice with Aβ25–35 injected into the lateral ventricle were used as two animal models of AD. Immunofluorescence staining and Western blot analysis showed that NLRP3 inflammasome-related proteins and inflammatory cytokines, such as IL-1α, IL-1β, IL-6, IL-12, and TNF-α, were increased and microglia were activated in the brains of both AD animal models. Endogenous overexpression of the APPswe gene and exogenous addition of Aβ25–35 increased the expression of NLRP3 inflammasome-related proteins, while exogenous Aβ25–35 intervention more significantly activated inflammation. Furthermore, LC3 was increased in the AD animal and cell models, and the level of Lamp1 decreased. After overexpression of the primary regulator of lysosomal biogenesis, TFEB, the lysosome protein Lamp1 was increased, and LC3 and inflammatory protein expression were decreased. These results suggest that the NLRP3 inflammasome-mediated inflammatory response is activated in AD animal and cell models, which may be related to the decline in autolysosome function. Overexpression of the TFEB protein can reduce the inflammatory response by improving autolysosome function in AD model cells.

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Section: Discussionmentioning

confidence: 99%

Enhanced Autolysosomal Function Ameliorates the Inflammatory Response Mediated by the NLRP3 Inflammasome in Alzheimer’s Disease

Zhou

Deng

Zhao

et al. 2021

Front. Aging Neurosci.

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“…Experiment 1 For evaluation of psychotic-like effects of dopaminergic drugs independent cohorts of 5-LO −/− and wild-type mice were acutely treated with both intraperitoneal amphetamine (10 mg/kg) or subcutaneous apomorphine (0.5 mg/kg) (Issy et al 2009(Issy et al , 2020 or with their respective controls (saline or distillated water). An additional group of 5-LO −/− mice received an intraperitoneal injection of glutamatergic antagonist MK801 (0.5 mg/kg; Issy et al 2018). Mice were subjected to the PPI test 15 min after pharmacological treatment (n = 7-8 per treatment).…”

Section: Experimental Designmentioning

confidence: 99%

“…Prepulse inhibition reaction The test was conducted simultaneously in two identical startle response systems (Med Associates, Inc., USA), as previously reported (Issy et al, 2018). A continuous acoustic signal provided a background white noise level of 65 dB.…”

Section: Experimental Designmentioning

confidence: 99%

Differential dopamine-mediated effects in the 5-lipoxygenase deficient mice

Issy,

Pedrazzi,

Nascimento

et al. 2024

Preprint

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The role of 5-lipoxygenase/leukotrienes on the central nervous system has been considered in both physiological end pathological states. Investigating the interaction between 5-lipoxygenase/leukotrienes and the dopaminergic system may provide better understanding of dopamine-related pathologies. This study aimed to investigate motor and non-motor dopamine-related responses in 5-lipoxygenase/leukotrienes-deficient mice. Pharmacological challenges of the dopaminergic system included amphetamine, apomorphine and reserpine treatment along with their respective effects on prepulse inhibition (PPI) response, general motor activity, and oral involuntary movements. Reserpine-treated mice were also investigated for their striatal glial markers’ expression (GFAP and Iba-1). 5-lipoxygenase/leukotrienes-deficient mice exhibited increased spontaneous locomotor activity, including horizontal and vertical exploratory activity, and stereotyped-like behavior compared to wild-type mice. This condition was attenuated by acute apomorphine treatment. Despite the absence of altered basal responses in the PPI there was a significant and selective decreased in susceptibility in amphetamine-induced PPI disruption in 5-lipoxygenase/leukotrienes-deficient mice. However, there was an increased vulnerability to reserpine-induced involuntary movements. There was no alteration in the basal expression of striatal GFAP and Iba-1 positive cells in 5-lipoxygenase/leukotrienes-deficient mice compared to wild-type mice. Reserpine treatment induced a significant increase in GFAP immunoreactivity in wild-type mice but this effect was absent in the 5-lipoxygenase deficient mice. The percentage of activated microglia was found to be significantly increased in reserpine-treated wild-type mice. This effect was absent in the 5-lipoxygenase/leukotrienes-deficient mice. Our results support the conception of a unique dopaminergic pathway phenotype in 5-lipoxygenase/leukotrienes-deficient mice. These findings suggest that leukotrienes may interfere with the orchestration of dopamine-mediated responses.

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“…Interestingly, several recent studies have shown that NOS2 regulates neuroinflammatory responses in the brain. For instance, the lipopolysaccharide (LPS)-induced increase in TNF-α levels is significantly reduced in nos2 knockout mice [ 8 ], and deletion of nos2 decreases the number of Iba-1/GFAP-positive cells in the brain compared with wild-type mice [ 9 ]. In addition, GFAP expression is diminished by one-third in NOS2 −/− mice compared with nTG mice [ 10 ].…”

Section: Main Textmentioning

confidence: 99%

Genetic deletion of nitric oxide synthase 2 ameliorates Parkinson’s disease pathology and neuroinflammation in a transgenic mouse model of synucleinopathy

et al. 2023

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Studies of mouse models of Alzheimer's disease (AD) have demonstrated that nitric oxide synthase 2 (NOS2) is involved in AD pathology. However, the effects of NOS2 on the pathology of Parkinson’s disease (PD) are not well studied. To address this gap, we examined the impact of NOS2 on disease-associated phenotypes in a mouse model of PD. Transgenic mice carrying the A53T mutation of α-synuclein (SynA53T) and newly generated double transgenic mice with deletion of NOS2 (SynA53T/NOS2−/−) were used. Compared with SynA53T mice, the loss of nos2 decreased α-synuclein phosphorylation at serine 129 and reduced α-synuclein-induced microglial and astrocyte activation in SynA53T/NOS−/− mice. Additionally, neuroinflammation-related gene clusters in the deep mesencephalic nucleus (DpMe) were altered in SynA53T/NOS−/− mice compared with SynA53T mice. Taken together, our results suggest that deletion of nos2 alleviates α-synuclein pathology and α-synuclein-associated neuroinflammatory responses in the brain.

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Differential behavioral and glial responses induced by dopaminergic mechanisms in the iNOS knockout mice

Cited by 5 publications

References 71 publications

Enhanced Autolysosomal Function Ameliorates the Inflammatory Response Mediated by the NLRP3 Inflammasome in Alzheimer’s Disease

Enhanced Autolysosomal Function Ameliorates the Inflammatory Response Mediated by the NLRP3 Inflammasome in Alzheimer’s Disease

Differential dopamine-mediated effects in the 5-lipoxygenase deficient mice

Genetic deletion of nitric oxide synthase 2 ameliorates Parkinson’s disease pathology and neuroinflammation in a transgenic mouse model of synucleinopathy

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