Photobiomodulation attenuates oligodendrocyte dysfunction and prevents adverse neurological consequences in a rat model of early life adversity

Abstract

Rationale: Adverse experiences in early life including abuse, trauma and neglect, have been linked to poor physical and mental health outcomes. Emerging evidence implies that those who experienced early life adversity (ELA) are more likely to develop cognitive dysfunction and depressive-like symptoms in adulthood. The molecular mechanisms responsible for the negative consequences of ELA, however, remain unclear. In the absence of effective management options, anticipatory guidance is the mainstay of ELA prevention. Furthermore, there is no available treatment that prevents or alleviates the neurologic sequelae of ELA, especially traumatic stress. Hence, the present study aims to investigate the mechanisms for these associations and evaluate whether photobiomodulation (PBM), a non-invasive therapeutic procedure, can prevent the negative cognitive and behavioral manifestations of ELA in later life. Methods: ELA was induced by repeated inescapable electric foot shock of rats from postnatal day 21 to 26. On the day immediately following the last foot shock, 2-min daily PBM treatment was applied transcranially for 7 consecutive days. Cognitive dysfunction and depression-like behaviors were measured by a battery of behavioral tests in adulthood. Subsequently, oligodendrocyte progenitor cells (OPCs) differentiation, the proliferation and apoptosis of oligodendrocyte lineage cells (OLs), mature oligodendrocyte, myelinating oligodendrocyte, the level of oxidative damage, reactive oxygen species (ROS) and total antioxidant capacity were measured and analyzed using immunofluorescence staining, capillary-based immunoassay (ProteinSimple®) and antioxidant assay kit. Results: The rats exposed to ELA exhibited obvious oligodendrocyte dysfunction, including a reduction in OPCs differentiation, diminished generation and survival of OLs, decreased OLs, and decreased matured oligodendrocyte. Furthermore, a deficit in myelinating oligodendrocytes was observed, in conjunction with an imbalance in redox homeostasis and accumulated oxidative damage. These alternations were concomitant with cognitive dysfunction and depression-like behaviors. Importantly, we found that early PBM treatment largely prevented these pathologies and reversed the neurologic sequelae resulting from ELA. Conclusions: Collectively, these findings provide new insights into the mechanism by which ELA affects neurological outcomes. Moreover, our findings support that PBM may be a promising strategy to prevent ELA-induced neurologic sequelae that develops later in life.

Early life adversity as a risk factor for cognitive impairment and Alzheimer’s disease

“…Paradigms that cause chronic early life stress involve exposing pups to multiple stressors or repetitive, prolonged stressors. In some paradigms, the pups are exposed to 3 to 4 distinct types of stressors, generally comprising forced swimming, physical restriction, placement on an elevated platform, and foot shock exposure in early postnatal days (PND) [ 41 , 42 ]. These combined factors can lead to significant physical and psychological stress [ 41 ].…”

“…In addition, a study by Park and colleagues found that two weeks of treadmill exercise from PND 21 to 35 significantly ameliorated cognitive impairment induced by maternal separation [ 203 ]. Furthermore, our recent work demonstrated that photobiomodulation, a non-invasive therapy, alleviated oligodendrocyte dysfunctions induced by early unpredictable electric foot shock and prevented adverse outcomes, indicating the therapeutic potential of this treatment for ELA [ 42 ].…”

Photobiomodulation of Neurogenesis through the Enhancement of Stem Cell and Neural Progenitor Differentiation in the Central and Peripheral Nervous Systems

“…PBM also influences astrocyte migration and protects astrocytes by maintaining astrocyte proliferation or differentiation; the increased co-expression of GFAP and BrdU/Ki67 indirectly supported this theory [64]. PBM also attenuated oligodendrocyte dysfunction and prevented adverse neurological consequences in a rat model of early life adversity [65].…”

Oligodendrocyte progenitor cells in Alzheimer’s disease: from physiology to pathology

“…A recent study revealed that in a rat model of early-life adversity, there is a decrease of OPC proliferation and differentiation, an increase of myelin loss, and elevated levels of oxidative damage. However, these changes can be reversed through early PBM treatment [266]. Unfortunately, no reported evidence regarding PBM therapy has been shown to specifically target OPCs in AD.…”