
FGF1 knockout mice exhibit impaired cognitive function. (1) Spontaneous alternation rate and total arm entries in the Y-maze test were significantly decreased in FGF1-/- mice. In the passive avoidance test, the time spent in the dark chamber on the second day was significantly reduced in FGF1-/- mice. The novel object recognition test indicated impaired short-term memory in FGF1-/- mice. Behavioral experiments demonstrated a decline in cognitive abilities in FGF1-/- mice compared to the wild-type group. (2) Transcriptomic analysis of the hippocampus revealed that FGF1 knockout leads to complex disorders in the nervous system, immune system, and lipid metabolism. (3) Lipidomic analysis of the hippocampus suggested lipid remodeling after FGF1 knockout, and related network analysis indicated that ceramide Cer(d18:1/22:0) plays a central role in related glycolipid metabolic pathways. (4) FGF1-/- mice showed activation of brain inflammatory responses, activation of the NF-κB/NLRP3 neuroinflammatory pathway, increased expression of brain inflammatory factors (IL-1β, TNF-α, IL-6), and impaired antioxidant stress function. Simultaneously, the blood-brain barrier was damaged, and peripheral immune cells invaded the central nervous system. (5) Neuronal expression was decreased and neuronal synaptic function was impaired in FGF1-/- mice. (6) Myelin regeneration function was impaired in FGF1-/- mice.
Schematic representation of four key genes involved in detox...