Palmitoylethanolamide prevents neurodevelopmental delay and early hippocampal damage after perinatal asphyxia

MARÍA INÉS HERRERA (PRIMERA AUTORÍA COMPARTIDA); UDOVIN LUCAS (PRIMERA AUTORÍA COMPARTIDA) ; KOBIEC TAMARA; CAMILA MENENDEZ-MAISSONAVE; NICOLÁS TORO URREGO; CARLOS F KUSNIER; KÖLLIKER FRERS, RODOLFO A.; MATILDE OTERO LOSADA; JUAN P LUACES; CAPANI FRANCISCO

Congreso; Neuroscience 2021 virtual congress, Participate Online, November 8-11; 2021

Perinatal asphyxia (PA) is a clinical condition brought by a birth temporary oxygen deprivation. This health problem continues to be a morbidity factor in neurodevelopment. Palmitoylethanolamide (PEA) is a neuromodulator well known for its protective effects in neurodevelopmental disorders, such as autism, albeit not deeply studied regarding its particular effects following PA. Recent evidence from our laboratory revealed perinatal treatment with PEA (10 mg/kg) could attenuate cytoskeletal alterations in CA1 hippocampal neurons and improve behavioral outcomes 1 month after PA induction (Herrera et al., 2018). In order to extend these findings, we intended to elucidate whether PEA might exert protective effects earlier on neurodevelopment. Pups (N=75) were tested daily for several reflexes and signs that indicate the maturation of the nervous system. Vulnerability of CA1 neurons was analyzed with Electron Microscopy. Microtubule associated protein-2 (MAP-2) was assessed by Immunohistochemistry and Western Blot at P21. During the first 3 weeks of life, asphyctic rats displayed a significant delay in the appearance of air righting, auditory startle, sensory eyelid, placing and grasp reflexes. A late onset of gait, negative geotaxis and eye opening was also observed. In addition, a slower performance of negative geotaxis was encountered in PA rats from postnatal day 11 (P11) to postnatal day 14 (P14). At P21, ultrastructural signs of neurodegeneration and MAP-2 deficit were found on CA1 hippocampal region. PEA treatment could ameliorate hippocampal damage and reverse the delay in the appearance of gait and motor reflexes. Therefore, PEA appears as a promising neuroprotective agent for the developing injured brain.*Herrera MI and Udovin LD have contributed equally to this work.