Pentylenetetrazole kindling impairs place recognition memory associated with suppressing proBDNF-mediated neural information flows at the hippocampal CA3-CA1 synapses.

Introduction: Mature brain-derived neurotrophic factor has long been known to as an epigenetic regulator. It is excessively secreted after status epilepticus, leading to a variety of permanent structural and functional changes in the brain. While its precursor forms proBDNF regulates nerve development, neural transmission and cognitive function, it is not fully known whether the expression of proBDNF is changed Methods: Here, we investigated changes in proBDNF levels in the hippocampus of the pentylenetetrazole (pentylenetetrazole)-induced epileptic rat model. Functional blocking of proBDNF singling and its related pathway in the hippocampal regions was conducted to explore the potential mechanisms. Meanwhile, local field potentials were recorded in the hippocampal CA3-CA1 pathway and the directionality of neural information flow (NIF) between two regions was evaluated. Results: We found that seizures were induced by PTZ-treated rats, which exhibited excessive proBDNF expression in the hippocampus only after undergoing behavioral training. Intra-hippocampal infusions of anti-proBDNF antibody into the CA1 but not the CA3 region could mitigate the PTZ-induced memory consolidation deficits and we confirmed the involvement of p75 Conclusion: Our findings are consistent with the hypothesis and provide the first direct evidence that the over-activation of proBDNF signaling represents a potential mechanism involved in neural dysfunction and NIF disruption leading to memory impairments in kindled animals.