Abstract

Recent evidence has established that consumption of High-fat diet (HFD)-induced obesity is associated with deficits in hippocampus-dependent memory/learning and mood states. Nevertheless the link between obesity and emotional disorders still remains to be elucidated. This issue is of particular interest during adolescence, which is important period for shaping learning/memory and mood regulation that can be sensitive to the detrimental effects of HFD. Our present study is focused to investigate behavioral and metabolic influences of short-term HFD intake in adolescent C57BL/6 mice. HFD caused weight gain, impaired glucose tolerance (IGT) and depression-like behavior as early as after 3weeks which was clearly proved by a decrease in number of groomings in the open field test (OFT) and an increase in immobility time in the tail suspension test (TST). In the 4th week HFD induced obese model was fully developed and above behavioral symptoms were more dominant (decrease in number of crossings and groomings and increase in immobility time in both FST and TST). At the end of 6th week hippocampal analysis revealed the differences in morphology (reduced Nissl positive neurons and decreased the 5-HT1A receptor expression), neuronal survival (increased cleaved caspase-3 expression), synaptic plasticity (down regulation of p-CREB and BDNF), and inflammatory responses (increase in expression of pro-inflammatory cytokines and decrease in expression of anti-inflammatory cyokines) in HFD mice. Our results demonstrate that, high-fat feeding of adolescent mice could provoke "depression-like" behavior as early as 3weeks and modulate structure, neuron survival and neuroinflammation in hippocampus as early as 6weeks proving that adolescent age is much prone to adverse effects of HFD, which causes obesity, behavioral differences, memory and learning deficiencies.

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