Light-at-night exposure affects brain development through pineal allopregnanolone-dependent mechanisms
Shogo Haraguchi1,2, Masaki Kamata1, Takuma Tokita1
1Laboratory of Integrative Brain Sciences, Department of Biology, Waseda University, Tokyo, Japan.
Elife
|October 1, 2019
Summary
Environmental light disrupts chick cerebellar development by altering pineal allopregnanolone (ALLO) synthesis, leading to Purkinje cell death. Restoring ALLO levels protected against this light-induced neurodegeneration.
Area of Science:
- Neuroscience
- Developmental Biology
- Chronobiology
Background:
- Environmental light, particularly light at night, is known to affect biological processes.
- The specific molecular pathways linking light exposure to cerebellar development remain unclear.
- Circadian rhythms play a crucial role in development and neuroprotection.
Purpose of the Study:
- To elucidate the molecular mechanisms by which light-at-night affects cerebellar development in early life.
- To investigate the role of pineal allopregnanolone (ALLO) in mediating these effects.
- To identify potential therapeutic targets for light-induced neurodevelopmental issues.
Main Methods:
- Utilized a chick model to study the effects of light-at-night on cerebellar development.
- Measured pineal allopregnanolone (ALLO) synthesis and its diurnal variations.
- Assessed Purkinje cell survival and the expression of neuroprotective factors like PACAP.
- Administered exogenous ALLO to evaluate its protective effects.
Main Results:
- Light-at-night disrupted the diurnal rhythm of pineal ALLO synthesis during early development.
- This disruption led to significant Purkinje cell death in the cerebellum.
- Exogenous ALLO administration successfully prevented light-induced Purkinje cell death.
- Reduced pineal ALLO synthesis correlated with decreased pituitary adenylate cyclase-activating polypeptide (PACAP) and repression of the cerebellar Adcyap1 gene.
Conclusions:
- Pineal allopregnanolone (ALLO) acts as a critical mediator linking environmental light conditions to cerebellar development.
- Disruption of diurnal ALLO synthesis by light-at-night causes neurodevelopmental deficits, specifically Purkinje cell death.
- Targeting pineal ALLO synthesis or its downstream pathways may offer neuroprotective strategies against environmental light disturbances.
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