Neuropeptide W30 improves hippocampal-dependent memory and synaptic transmission by promoting NOS1 and CREB expression

SANTIAGO BIANCONI; VERÓNICA DÍAZ; MARIA BELEN PORETTI; EMILSE ARTUR DE VILLARMOIS; ANA CAROLINA MARTINI; HELGI B. SCHIOTH; MARIELA F PEREZ; VALERIA PAOLA CARLINI

Buenos Aires

Congreso; Reunión Conjunta de Sociedades de Biociencias (SAIC, SAIB, SAI, SAFE, SAH, SAP, SAB, SAFIS, SAA, SAB); 2017

SAIC

Homeostatic regulation of feeding and energy balance involvescognitive, emotional, sensorial and autonomic events, as well as theactivity of a highly integrated and redundant neurohumoral system.Neuropeptide W (NPW) is part of this complex net. There are twomature forms derived from a common precursor peptide, pro-NPW,by proteolytic processing: NPW30 (the 30 amino acids form) andNPW23 (consisting of 23 amino acids). The peptide and its receptorsare present in the rat hippocampus, amygdala, hypothalamus,and pituitary. We have previously found that hippocampal administrationof NPW30 increased latency time in the step-down test.Objective: to assess the effect of hippocampal NPW30 acute administrationon neuroplasticity and expression of several genes relatedto the molecular cascade of memory in rat hippocampus. Male adultrats were infused into the hippocampus with artificial cerebrospinalfluid (Control group) or NPW30 (0.3 and 3 nmol/μl) and 24h later,the hippocampus was dissected to perform electrophysiological procedure(n=5/each group) or RT-PCR (n=10/each group). Statistics:Student?s t-test or ANOVA followed by Bonferroni. The highest doseof NPW30 reduced the threshold to generate long term potentiation(LTP) (NPW30, 3 nmol/μl: 31.67±5.43 Hz vs. Control: 90.00±17.32Hz; P<0.05) and increased the relative expression of cyclic AMP responseelement binding protein (CREB) 1b (F(27,2)=8.07; P<0.05)and neuronal nitric oxide synthase (NOS1) (F(23,2)=9.31; P<0.05).It has been demonstrated that NOS1 activity is relevant in earlystages of memory formation, and CREB is a transcription factor thatplays a key role in the hippocampal plasticity, especially in LTP inductionand maintenance and long term memory establishment. Inconclusion, these findings suggest that NOS1 and CREB participatein the mechanism by which NPW30 can modulate neuroplasticityand behavioral expression of memory