Neuroprotective and neurodegenerative effects of the chronic expression of tumor necrosis factor α in the nigrostriatal dopaminergic circuit of adult mice

Chertoff, Mariela; Paolo, N. Di; Schoeneberg, A.; Depino, Amaicha Mara; Ferrari, Carina Cintia; Wurst, Wolfgang; Pfizenmaier, Klaus; Eisel, Ulrich; Pitossi, Fernando Juan

doi:10.1016/j.expneurol.2010.11.010

Cited by 63 publications

(56 citation statements)

References 79 publications

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“…These results are in agreement with previous findings showing that Sildenafil reduces oxidative stress and inflammatory injuries of the kidney in streptozotocin-diabetic rats [27] and after ischemia and reperfusion [28]. Expression of pro-inflammatory cytokines in injured nerves may have both beneficial and detrimental effects on nerve regeneration or neuropathic pain induction [29,30,31]. In the present manuscript, we demonstrated that BCNR up-regulates the expression of several pro-inflammatory cytokines in the pelvic ganglia; SIL treatment was able to reduce these levels back to that of sham operated animals.…”

Section: Discussionsupporting

confidence: 92%

Sildenafil Attenuates Inflammation and Oxidative Stress in Pelvic Ganglia Neurons after Bilateral Cavernosal Nerve Damage

Garcia

Hlaing

Gutierrez

et al. 2014

IJMS

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Erectile dysfunction is a common complication for patients undergoing surgeries for prostate, bladder, and colorectal cancers, due to damage of the nerves associated with the major pelvic ganglia (MPG). Functional re-innervation of target organs depends on the capacity of the neurons to survive and switch towards a regenerative phenotype. PDE5 inhibitors (PDE5i) have been successfully used in promoting the recovery of erectile function after cavernosal nerve damage (BCNR) by up-regulating the expression of neurotrophic factors in MPG. However, little is known about the effects of PDE5i on markers of neuronal damage and oxidative stress after BCNR. This study aimed to investigate the changes in gene and protein expression profiles of inflammatory, anti-inflammatory cytokines and oxidative stress related-pathways in MPG neurons after BCNR and subsequent treatment with sildenafil. Our results showed that BCNR in Fisher-344 rats promoted up-regulation of cytokines (interleukin- 1 (IL-1) β, IL-6, IL-10, transforming growth factor β 1 (TGFβ1), and oxidative stress factors (Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, Myeloperoxidase (MPO), inducible nitric oxide synthase (iNOS), TNF receptor superfamily member 5 (CD40) that were normalized by sildenafil treatment given in the drinking water. In summary, PDE5i can attenuate the production of damaging factors and can up-regulate the expression of beneficial factors in the MPG that may ameliorate neuropathic pain, promote neuroprotection, and favor nerve regeneration.

show abstract

Section: Discussionsupporting

confidence: 92%

Sildenafil Attenuates Inflammation and Oxidative Stress in Pelvic Ganglia Neurons after Bilateral Cavernosal Nerve Damage

Garcia

Hlaing

Gutierrez

et al. 2014

IJMS

View full text Add to dashboard Cite

show abstract

“…In addition, the proinflammatory cytokine tumor necrosis factor alpha (TNF-α) released by astrocytes triggers the GDNF release from reactive astrocytes in vitro (Kuno et al, 2006). This would not only suggest the activation of an autocrine anti-inflammatory loop but also support the notion that TNF-α acts as a gliotransmitter that may trigger plasticity processes involving GDNF (Fellin, 2009) in addition to the prevention of secondary neuronal degeneration due to inactivity (Chertoff et al, 2011). Moreover, increased levels of GDNF released from astrocytes may directly affect the formation of synapses as well as dendritic and axonal growth as observed in the models of Parkinson's disease (Nakajima et al, 2001).…”

Section: Discussionmentioning

confidence: 95%

Dopamine receptor activation increases glial cell line-derived neurotrophic factor in experimental stroke

Kuric

Wieloch

Ruscher

2013

Experimental Neurology

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“…Chertoff and colleagues have also explored the concept of TNF-α playing dual roles in PD pathophysiology. Young 2-3 month-old mice subjected to 6-OHDA with constitutive, low-level expression of TNF-α are spared in respect to nigrostriatial degeneration, whereas overt neuronal loss and inflammatory responses occurs in mice overexpressing TNF-α, indicating that the level and timing of TNF-α plays a pivotal role in the progression of disease (Chertoff et al 2011). Collectively, these data demonstrate that the development of anti-TNF-α PD therapies requires a highly tuned and selective strategy based upon assiduous examination of the dependence of disease stage, TNF-α levels, cellular context, and individual receptor involvement in multiple models of PD.…”

Section: Parkinson's Diseasementioning

confidence: 99%

Tumor Necrosis Factor-alpha and the Roles it Plays in Homeostatic and Degenerative Processes Within the Central Nervous System

Montgomery

Bowers

2011

J Neuroimmune Pharmacol

303

181

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Tumor Necrosis Factor-alpha (TNF-α) is a prototypic pro-inflammatory cytokine involved in the innate immune response. TNF-α ligation and downstream signaling with one of its cognate receptors, TNF-RI or TNF-RII, modulates fundamental processes in the brain including synapse formation and regulation, neurogenesis, regeneration, and general maintenance of the central nervous system (CNS). During states of chronic neuroinflammation, extensive experimental evidence implicates TNF-α as a key mediator in disease progression, gliosis, demyelination, inflammation, blood-brain-barrier deterioration, and cell death. This review explores the complex roles of TNF-α in the CNS under normal physiologic conditions and during neurodegeneration. We focus our discussion on Multiple Sclerosis, Parkinson's disease, and Alzheimer's disease, relaying the outcomes of preclinical and clinical testing of TNF-α directed therapeutic strategies, and arguing that despite the wealth of functions attributed to this central cytokine, surprisingly little is known about the cell type- and stage-specific roles of TNF-α in these debilitating disorders.

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Neuroprotective and neurodegenerative effects of the chronic expression of tumor necrosis factor α in the nigrostriatal dopaminergic circuit of adult mice

Abstract: Neuroprotective and neurodegenerative effects of the chronic expression of tumor necrosis factor alpha in the nigrostriatal dopaminergic circuit of adult mice Chertoff, M.; Di Paolo, N.; Schoeneberg, A.; Depino, A.; Ferrari, C.; Wurst, W.; Pfizenmaier, K.; Eisel, Ulrich; Pitossi, F.

Cited by 63 publications

References 79 publications

Sildenafil Attenuates Inflammation and Oxidative Stress in Pelvic Ganglia Neurons after Bilateral Cavernosal Nerve Damage

Sildenafil Attenuates Inflammation and Oxidative Stress in Pelvic Ganglia Neurons after Bilateral Cavernosal Nerve Damage

Dopamine receptor activation increases glial cell line-derived neurotrophic factor in experimental stroke

Tumor Necrosis Factor-alpha and the Roles it Plays in Homeostatic and Degenerative Processes Within the Central Nervous System

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