Major depressive disorder (MDD) is one of the leading forms of
psychiatric disorders, characterized by aversion to mobility,
neurotransmitter deficiency, and energy metabolic decline.
Low-level laser therapy (
LLLT) has been investigated in a variety of
neurodegenerative disorders associated with
mitochondrial dysfunction and functional impairments. The goal of this study was to examine the effect of
LLLT on depression-like behaviors and to explore the potential mechanism by detecting mitochondrial function following
LLLT. Depression models in space restriction mice and Abelson helper integration site-1 (Ahi1) knockout (KO) mice were employed in this work. Our results revealed that
LLLT effectively improved depression-like behaviors, in the two depression mice models, by decreasing immobility duration in behavioral despair tests. In addition,
ATP biosynthesis and the level of mitochondrial complex IV expression and activity were significantly elevated in prefrontal cortex (PFC) following
LLLT. Intriguingly,
LLLT has no effects on
ATP content and mitochondrial complex I-IV levels in other tested brain regions, hippocampus and hypothalamus. As a whole, these findings shed light on a novel strategy of transcranial
LLLT on depression improvement by ameliorating
neurotransmitter abnormalities and promoting mitochondrial function in PFC. The present work provides concrete groundwork for further investigation of
LLLT for depression treatment.