aFGF Promotes Neurite Growth by Regulating GSK3β-CRMP2 Signaling Pathway in Cortical Neurons Damaged by Amyloid-β

2019 ◽  
Vol 72 (1) ◽  
pp. 97-109 ◽  
Author(s):  
Qin Cao ◽  
Tian Meng ◽  
Jianhui Man ◽  
Dong Peng ◽  
Hongxia Chen ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Cortical Neurons ◽  
Amyloid Β ◽  
Neurite Growth

scholarly journals Age-Dependent Decline in Neuron Growth Potential and Mitochondria Functions in Cortical Neurons

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1625
Author(s):  
Theresa C. Sutherland ◽  
Arthur Sefiani ◽  
Darijana Horvat ◽  
Taylor E. Huntington ◽  
Yuanjiu Lei ◽  
...  
Keyword(s):  
Cortical Neurons ◽  
Traumatic Injury ◽  
Axon Growth ◽  
Neurite Growth ◽  
Growth Potential ◽  
Mitochondrial Functions ◽  
Cord Injury ◽  
Age Dependent ◽  
Mitochondria Functions ◽  
The Impact

The age of incidence of spinal cord injury (SCI) and the average age of people living with SCI is continuously increasing. However, SCI is extensively modeled in young adult animals, hampering translation of research to clinical applications. While there has been significant progress in manipulating axon growth after injury, the impact of aging is still unknown. Mitochondria are essential to successful neurite and axon growth, while aging is associated with a decline in mitochondrial functions. Using isolation and culture of adult cortical neurons, we analyzed mitochondrial changes in 2-, 6-, 12- and 18-month-old mice. We observed reduced neurite growth in older neurons. Older neurons also showed dysfunctional respiration, reduced membrane potential, and altered mitochondrial membrane transport proteins; however, mitochondrial DNA (mtDNA) abundance and cellular ATP were increased. Taken together, these data suggest that dysfunctional mitochondria in older neurons may be associated with the age-dependent reduction in neurite growth. Both normal aging and traumatic injury are associated with mitochondrial dysfunction, posing a challenge for an aging SCI population as the two elements can combine to worsen injury outcomes. The results of this study highlight this as an area of great interest in CNS trauma.

scholarly journals Neuron-specific activation of necroptosis signaling in multiple sclerosis cortical grey matter

2021 ◽  
Vol 141 (4) ◽  
pp. 585-604 ◽  
Author(s):  
Carmen Picon ◽  
Anusha Jayaraman ◽  
Rachel James ◽  
Catriona Beck ◽  
Patricia Gallego ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Signaling Pathway ◽  
Cortical Neurons ◽  
Grey Matter ◽  
Molecular Mechanisms ◽  
Fold Increase ◽  
Cell Types ◽  
Meningeal Inflammation ◽  
Cortical Grey Matter

AbstractSustained exposure to pro-inflammatory cytokines in the leptomeninges is thought to play a major role in the pathogenetic mechanisms leading to cortical pathology in multiple sclerosis (MS). Although the molecular mechanisms underlying neurodegeneration in the grey matter remain unclear, several lines of evidence suggest a prominent role for tumour necrosis factor (TNF). Using cortical grey matter tissue blocks from post-mortem brains from 28 secondary progressive MS subjects and ten non-neurological controls, we describe an increase in expression of multiple steps in the TNF/TNF receptor 1 signaling pathway leading to necroptosis, including the key proteins TNFR1, FADD, RIPK1, RIPK3 and MLKL. Activation of this pathway was indicated by the phosphorylation of RIPK3 and MLKL and the formation of protein oligomers characteristic of necrosomes. In contrast, caspase-8 dependent apoptotic signaling was decreased. Upregulation of necroptotic signaling occurred predominantly in macroneurons in cortical layers II–III, with little expression in other cell types. The presence of activated necroptotic proteins in neurons was increased in MS cases with prominent meningeal inflammation, with a 30-fold increase in phosphoMLKL+ neurons in layers I–III. The density of phosphoMLKL+ neurons correlated inversely with age at death, age at progression and disease duration. In vivo induction of chronically elevated TNF and INFγ levels in the CSF in a rat model via lentiviral transduction in the meninges, triggered inflammation and neurodegeneration in the underlying cortical grey matter that was associated with increased neuronal expression of TNFR1 and activated necroptotic signaling proteins. Exposure of cultured primary rat cortical neurons to TNF induced necroptosis when apoptosis was inhibited. Our data suggest that neurons in the MS cortex are dying via TNF/TNFR1 stimulated necroptosis rather than apoptosis, possibly initiated in part by chronic meningeal inflammation. Neuronal necroptosis represents a pathogenetic mechanism that is amenable to therapeutic intervention at several points in the signaling pathway.

Protection of amyloid β protein (25–35)-induced neurotoxicity by methanol extract of Smilacis chinae rhizome in cultured rat cortical neurons

2006 ◽  
Vol 106 (2) ◽  
pp. 230-237 ◽  
Author(s):  
Ju Yeon Ban ◽  
Soon Ock Cho ◽  
Sang Bum Koh ◽  
Kyung-Sik Song ◽  
KiWhan Bae ◽  
...  
Keyword(s):  
Cortical Neurons ◽  
Methanol Extract ◽  
Amyloid Β ◽  
Amyloid Β Protein ◽  
Β Protein ◽  
Rat Cortical Neurons

3,4-Dihydroxybenzoic acid from Smilacis chinae rhizome protects amyloid β protein (25–35)-induced neurotoxicity in cultured rat cortical neurons

2007 ◽  
Vol 420 (2) ◽  
pp. 184-188 ◽  
Author(s):  
Ju Yeon Ban ◽  
Soon Ock Cho ◽  
So-Young Jeon ◽  
KiHwan Bae ◽  
Kyung-Sik Song ◽  
...  
Keyword(s):  
Cortical Neurons ◽  
Amyloid Β ◽  
Amyloid Β Protein ◽  
Dihydroxybenzoic Acid ◽  
Β Protein ◽  
Rat Cortical Neurons

Amyloid β induces phosphorylation and translocation of MARCKS through tyrosine kinase-activated PKC-δ signaling pathway in microglia

2001 ◽  
pp. 229-232
Author(s):  
Masamichi Nakai ◽  
Satoshi Tanimukai ◽  
Keiko Yagi ◽  
Naoaki Saito ◽  
Hiroshi Hasegawa ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Signaling Pathway ◽  
Amyloid Β

scholarly journals The Age-Dependent Decline in Neuron Growth Potential in the CNS is Associated with an Age-Related Dysfunction of Neuronal Mitochondria

2021 ◽  
Author(s):  
Theresa C. Sutherland ◽  
Arthur Sefiani ◽  
Darijana Horvat ◽  
Taylor E. Huntington ◽  
Yuanjiu Lei ◽  
...  
Keyword(s):  
Cortical Neurons ◽  
Traumatic Injury ◽  
Axon Growth ◽  
Neurite Growth ◽  
Growth Potential ◽  
Age Related ◽  
Mitochondrial Functions ◽  
Cord Injury ◽  
Age Dependent ◽  
Neuron Growth

The age of incidence of Spinal Cord Injury (SCI) and the average age of people living with SCI is continuously increasing. In contrast, SCI is extensively modelled in young adult animals, hampering translation of research to clinical application. While there has been significant progress in manipulating axon growth after injury, how it is impacted by aging impacts this is still unknown. Aging is associated with a decline in mitochondrial functions, whereas mitochondria are essential to successful neurite and axon growth. Using isolation and culture of adult cortical neurons, we have analyzed mitochondrial changes in 2-, 6-, 12- and 18-month mice. We observed reduced neurite growth in older neurons. Older neurons also showed dysfunctional respiration, reduced membrane potential, and altered mitochondrial membrane transport proteins; however mitochondrial DNA (mtDNA) abundance and cellular ATP were increased. Taken together, these data suggest dysfunctional mitochondria in older neurons are involved in the age-dependent reduction in neuron growth. Both normal aging and traumatic injury are associated with mitochondrial dysfunction, posing a challenge for an aging SCI population as the two elements can compound one another to worsen injury outcomes. The results of this study highlight this as an area of great interest in CNS trauma.

Sign in / Sign up

Export Citation Format

Share Document