Stress　is　considered　as　a　major　cause　of　depression.　C-Jun　N-terminal　kinase　(JNK)　is　a　member　of　the　stress-induced　mitogen　activated　protein　(MAP)　kinase　family　which　is　often　activated　through　phosphorylation.　Clinical　studies　and　animal　experiments　have　found　that　abnormal　phosphorylation/activation　of　JNK　exists　in　the　occurrence　of　various　psychiatric　diseases.　Recently,　several　studies　linked　JNK　kinase　activity　to　depression.　However,　whether　excessive　activation　of　JNK　activity　is　directly　responsible　for　the　occurrence　of　depression　and　the　underlying　mechanisms　remain　unclear.　Here,　we　constructed　a　conditional　transgenic　mouse　which　is　specifically　expressing　MKK7-JNK1　(CAJNK1)　in　the　central　nervous　system.　CAJNK1　mice　showed　activation　of　JNK　and　lead　to　depression-like　behavior　in　mice.　Transcriptome　analysis　indicates　reduced　expression　of　synaptic-associated　genes　in　CAJNK1　mice　brains.　Consistently,　we　found　abnormal　dendritic　spine　development　and　PSD95　downregulation　in　CAJNK1　hippocampal　neurons.　Our　studies　provide　compelling　evidence　that　activation　of　JNK　as　an　intrinsic　factor　leading　to　depression-like　behavior　in　mice　provides　direct　clues　for　targeting　the　JNK　activity　as　a　potential　therapeutic　strategy　for　depression.