ABSTRACT
Photobiomodulation is a non-pharmacological tool widely used to reduce inflammation in many tissues. However, little is known about its effects on the inflammatory response in the aged brain. We conducted the study to examine anti-inflammatory effects of photobiomodulation in aging brains. We used aged rats (20 months old) with control (handled, laser off) or transcranial laser (660 nm wavelength, 100 mW power) treatments for 10 consecutive days and evaluated the level of inflammatory cytokines and chemokines, and the expression and activation of intracellular signaling proteins in the cerebral cortex and the hippocampus. Inflammatory analysis showed that aged rats submitted to transcranial laser treatment had increased levels of IL-1alpha and decreased levels of IL-5 in the cerebral cortex. In the hippocampus, the laser treatment increased the levels of IL-1alpha and decreased levels of IL-5, IL-18, and fractalkine. Regarding the intracellular signaling proteins, a reduction in the ERK and p38 expression and an increase in the STAT3 and ERK activation were observed in the cerebral cortex of aged rats from the laser group. In addition, the laser treatment increased the hippocampal expression of p70S6K, STAT3, and p38 of aged rats. Taken together, our data indicate that transcranial photobiomodulation can improve the inflammatory response and the activation of intracellular signaling proteins linked to vascular function and cell survival in the aged brain.
Subject(s)
Aging/metabolism , Cell Survival/physiology , Intracellular Signaling Peptides and Proteins/metabolism , Low-Level Light Therapy , Neuroinflammatory Diseases/therapy , Animals , Brain/metabolism , Cytokines/metabolism , Male , Neuroinflammatory Diseases/metabolism , Rats , Rats, WistarABSTRACT
Aging is often accompanied by exacerbated activation of cell death-related signaling pathways and decreased energy metabolism. We hypothesized that transcranial near-infrared laser may increase intracellular signaling pathways beneficial to aging brains, such as those that regulate brain cell proliferation, apoptosis, and energy metabolism. To test this hypothesis, we investigated the expression and activation of intracellular signaling proteins in the cerebral cortex and hippocampus of aged rats (20 months old) treated with the transcranial near-infrared laser for 58 consecutive days. As compared to sham controls, transcranial laser treatment increased intracellular signaling proteins related to cell proliferation and cell survival, such as signal transducer and activator of transcription 3 (STAT3), extracellular signal-regulated protein kinase (ERK), c-Jun N-terminal kinase (JNK), p70 ribosomal protein S6 kinase (p70S6K) and protein kinase B (PKB), also known as Akt that is linked to glucose metabolism. In addition, ERK is linked to memory, while ERK and JNK signaling pathways regulate glucose metabolism. Specifically, the laser treatment caused the activation of STAT3, ERK, and JNK signaling proteins in the cerebral cortex. In the hippocampus, the laser treatment increased the expression of p70S6K and STAT3 and the activation of Akt. Taken together, the data support the hypothesis that transcranial laser photobiomodulation improves intracellular signaling pathways linked to cell survival, memory, and glucose metabolism in the brain of aged rats.
ABSTRACT
As malformações linfáticas são distúrbios do desenvolvimento caracterizados pelo crescimento excessivo de vasos linfáticos. Essa condição acontece principalmente em região de cabeça e pescoço devido à presença fisiológica de grande concentração de vasos linfáticos na região. As malformações linfáticas podem ocorrer de maneira isolada ou associadas a síndromes como de CLOVES e Klippel-Trènaunay. A presença de mutações no gene PIK3CA e a ativação das vias PI3K/AKT e MAPK/ERK pode ocorrer tanto nas malformações linfáticas esporádicas, como naquelas associadas a síndromes. As mutações em PIK3CA ocorrem nos éxons 10 e 20, sendo as mutações no códon 1047 (éxon 20) as mais frequente nas malformações linfáticas esporádicas. No entanto, em malformações linfáticas orais não se sabe se estes fenômenos ocorrem. O objetivo deste estudo foi avaliar a presença de mutações no códon 1047 do gene PIK3CA e avaliar a ativação das vias PI3K/AKT e MAPK/ERK em amostras de malformações linfáticas orais. Uma amostra de conveniência de 14 tecidos de malformações linfáticas orais fixados em formol e embebidos em parafina foram submetidas a reações de imuno-histoquímica para as formas fosforiladas de AKT1 (pAKT-Ser473) e ERK1/2 (pERK1/2-Thr202/Tyr204), marcadores de ativação das vias PI3K/AKT e MAPK/ERK, respectivamente. Quatro destas amostras foram submetidas a Sequenciamento de Sanger para o códon 1047 do gene PIK3CA. Foram observados padrões de marcação positivas para pAKT1 e pERK1/2 nas células endoteliais de todas as amostras de malformações linfáticas orais avaliadas. Todas as amostras submetidas ao Sequenciamento de Sanger apresentaram sequência selvagem para a região de interesse. Com os resultados obtidos sugere-se que as vias PI3K/AKT e MAPK/ERK estão envolvidas na patogênese das malformações linfáticas orais.
Lymphatic malformations are developmental disorders characterized by excessive growth of lymphatic vessels. This condition occurs mainly in the head and neck region due to the physiological presence of high concentration of lymphatic vessels in the region. Lymphatic malformations may occur in isolation or associated with syndromes such as CLOVES and Klippel-Trènaunay. Mutations in the PIK3CA gene and activation of the PI3K/AKT and MAPK/ERK pathways may occur both in sporadic lymphatic malformations and in those associated with syndromes. Mutations in hotspot 1047 are the most frequently found in isolated lymphatic malformation. However, in oral lymphatic malformations it is not known whether these mutations occur. The aim of this study was to evaluate the presence of mutations in codon 1047 of the PIK3CA gene and to evaluate the activation of PI3K/AKT and MAPK/ERK pathways in samples of oral lymphatic malformations. A convenience sample of 14 tissues of oral lymphatic malformations formalin fixed paraffin embedded were submitted to immunohistochemistry reactions to the phosphorylated forms of AKT1 (pAKT-Ser473) and ERK1/2 (pERK1/2-Thr202/Tyr204), activation markers of PI3K/AKT and MAPK/ERK pathways, respectively. Four of these samples were submitted to Sanger Sequencing for codon 1047 of the PIK3CA gene. Positive marking patterns for pAKT1 and pERK1/2 were observed in the endothelial cells of all samples of oral lymphatic malformations evaluated. All samples submitted to Sanger Sequencing were wild type for the region of interest. With the results obtained it is suggested that the PI3K/AKT and MAPK/ERK pathways are involved in the pathogenesis of oral lymphatic malformations.