Induction of hippocampal neurogenesis by a tolerogenic peptide that ameliorates lupus manifestations

Telerman, Alona; Lapter, Smadar; Sharabi, Amir; Zinger, Heidy; Mozes, Edna

doi:10.1016/j.jneuroim.2010.11.001

Cited by 19 publications

(12 citation statements)

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“…Among the different members of the family of neurotrophic factors (neurotrophins), the most attention has been focused on the stimulatory effect of PBM on brain derived neurotrophic factor (BDNF), neuronal growth factor (NGF), and glial cell-derived neurotrophic factor (GDNF). Increased expression of neurotrophins such as BDNF and NGF may account for observations of stimulation of neurogenesis and synaptogenesis [167]. Augmentation of BDNF expression could lead to reduced atrophy of cortical dendrites in the central nervous system (CNS) during the progression of AD [168].…”

Section: Neurobiological Impactsmentioning

confidence: 99%

Brain Photobiomodulation Therapy: a Narrative Review

et al. 2018

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Brain photobiomodulation (PBM) therapy using red to near-infrared (NIR) light is an innovative treatment for a wide range of neurological and psychological conditions. Red/NIR light is able to stimulate complex IV of the mitochondrial respiratory chain (cytochrome c oxidase) and increase ATP synthesis. Moreover, light absorption by ion channels results in release of Ca and leads to activation of transcription factors and gene expression. Brain PBM therapy enhances the metabolic capacity of neurons and stimulates anti-inflammatory, anti-apoptotic, and antioxidant responses, as well as neurogenesis and synaptogenesis. Its therapeutic role in disorders such as dementia and Parkinson's disease, as well as to treat stroke, brain trauma, and depression has gained increasing interest. In the transcranial PBM approach, delivering a sufficient dose to achieve optimal stimulation is challenging due to exponential attenuation of light penetration in tissue. Alternative approaches such as intracranial and intranasal light delivery methods have been suggested to overcome this limitation. This article reviews the state-of-the-art preclinical and clinical evidence regarding the efficacy of brain PBM therapy.

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Section: Neurobiological Impactsmentioning

confidence: 99%

Brain Photobiomodulation Therapy: a Narrative Review

et al. 2018

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“…Further studies are needed to identify the pathways/factors by which neuronal damage interacts with systemic immune activation. Although astrocytes did not exhibit increased activation or colocalization with synaptic terminals, we cannot completely rule out their contribution to this process, as their functions of nerve support and neurotrophy differ from those of microglia 61,62 . In NPSLE, increased intracerebral C1q burden co-clustered with reactive microglia, as crucial events in neuronal stripping, offering opportunities for pharmacological interventions.…”

Section: Discussionmentioning

confidence: 71%

Neuronal NR4A1 and complement coordinate synaptic stripping by microglia in lupus

Han¹,

Xu²,

Fang³

et al. 2020

Preprint

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Up to 75% of systematic lupus erythematosus (SLE) patients experience neuropsychiatric (NP) symptoms, called neuropsychiatric SLE (NPSLE), yet the underlying mechanisms remain elusive. Here we showed that complement-coordinated elimination of synapses participated in NPSLE in MRL/lpr mice, a lupus-prone murine model. We demonstrated that lupus mice developed increased anxiety-like behaviors and persistent phagocytic microglia reactivation before overt peripheral lupus pathology. In lupus brain, C1q was increased and localized at synaptic terminals, causing the apposition of phagocytic microglia, ensuing synaptic loss, and neurological disease. We further determined that neuronal Nr4a1 signaling was essential for attracting C1q synaptic deposition and then apposition of phagocytic microglia, resulting in synaptic loss and neurological disease. Minocycline-deactivated microglia, antibody-blocked C1q, or neuronal Nr4a1 restored protected lupus mice from synapse loss and NP manifestations. Our findings revealed an active role of neurons in coordinating microglia-mediated synaptic loss and highlight neuronal Nr4a1 and C1q as critical components amenable to pharmacological intervention in NPSLE.

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“…The extracellular signal-regulated kinase (ERK) is activated by MEK in response to growth stimuli [19] and much evidence exists that the ERK pathway plays a role in progenitor cell proliferation or differentiation in a number of model systems. For example, the ERK pathway is involved in neurogenesis, neurite outgrowth, and neuronal survival induced by either neurotrophic factors [20,21] or pharmacological agents such as valproate [22] or lithium [86] and it has been proven that ERK activation promotes hippocampal neurogenesis in vivo [26,27] and in vitro [28,29]. Similarly, PKA regulation of transcription via CREB has been associated with growth factor-dependent neurogenesis, cell survival, synaptic transmission and cognitive function in the nervous system [23-25].…”

Section: Discussionmentioning

confidence: 99%

“…One of the most well know transcriptional regulators of BDNF gene expression is the cyclic AMP responsive element binding protein (CREB); activation of which can be mediated by the cAMP-dependent protein kinase (PKA), the mitogen-activated protein kinase (MAPK) pathway or the Ca 2+ /calmodulin-dependent protein kinases (CaMKs), among others, depending on the activating signal and cell type [15-17]. These kinases have been reported to mediate cell proliferation and neurogenesis as well as neurite outgrowth, synaptic transmission and neuronal survival in a number of model systems [18-25] and specifically to promote hippocampal neurogenesis both in vivo [26,27] and in vitro [28,29]. …”

Section: Introductionmentioning

confidence: 99%

Transient domoic acid excitotoxicity increases BDNF expression and activates both MEK- and PKA-dependent neurogenesis in organotypic hippocampal slices

Pérez-Gómez

Tasker

2013

BMC Neurosci

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BackgroundWe have previously reported evidence of cell proliferation and increased neurogenesis in rat organotypic hippocampal slice cultures (OHSC) after a transient excitotoxic injury to the hippocampal CA1 area induced by low concentrations of the AMPA/kainate agonist domoic acid (DOM). An increased baseline rate of neurogenesis may contribute to recovery from DOM-induced mild injury but the intracellular mechanism(s) responsible for neuronal proliferation remain unclear. The current study investigated the key intracellular pathways responsible for DOM-induced neurogenesis in OHSC including the effects of transient excitotoxicity on the expression of brain-derived neurotrophic factor (BDNF), a well-known regulator of progenitor cell mitosis.ResultsApplication of a low concentration of DOM (2 μM) for 24 h followed by recovery induced a significant and long lasting increase in BDNF protein levels expressed by both neurons and microglial cells. Furthermore, the mild DOM toxicity stimulated both PKA and MEK-dependent intracellular signaling cascades and induced a significant increase in BDNF- transcription factor CREB activation and BDNF-receptor TrkB expression. Coexposure to specific inhibitors of PKA and MEK phosphorylation resulted in a significant decrease in the neurogenic marker doublecortin.ConclusionsOur results suggest that transient excitotoxic insult induced by DOM produces BDNF and CREB overexpression via MEK and PKA pathways and that both pathways mediate, at least in part, the increased neural proliferation resulting from mild excitotoxicity.

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Induction of hippocampal neurogenesis by a tolerogenic peptide that ameliorates lupus manifestations

Cited by 19 publications

References 50 publications

Brain Photobiomodulation Therapy: a Narrative Review

Brain Photobiomodulation Therapy: a Narrative Review

Neuronal NR4A1 and complement coordinate synaptic stripping by microglia in lupus

Transient domoic acid excitotoxicity increases BDNF expression and activates both MEK- and PKA-dependent neurogenesis in organotypic hippocampal slices

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