SHORT AND LONG TERM MODIFICATIONS IN CENTRAL NERVOUS SYSTEM INDUCED BY PERINATAL ASPHYXIA

RODOLFO KOLLIKER-FRERS , CARLOS KUSNIER(1) , PAULA ABBAS(1), LUCAS UDOVIN(1), NICOLAS TORO-URREGO(1), TAMARA KOBIEC(1,2), CLAUDIA MARDARAZ(1) , MATILDE OTERO-LOSADA (1), FRANCISCO CAPANI

Congreso; Interamerican Cnngress of Microscopy; 2022

SHORT AND LONG TERM MODIFICATIONS IN CENTRAL NERVOUS SYSTEM INDUCED BY PERINATAL ASPHYXIA Rodolfo Kolliker-Frers (1,2), Juan Pablo Luaces (1) , Maria Inés Herrera (1, 2), , Sofia Bordet (1,2) , Guenson Chevallier(1), Carlos Kusnier(1) , Paula Abbas(1), Lucas Udovin(1), Nicolas Toro-Urrego(1), Tamara Kobiec(1,2), Claudia Mardaraz(1) , Matilde Otero-Losada (1), Francisco Capani (1, 2, 3).(1)Centro de Altos Estudios en Ciencias Humanas y de la Salud, Universidad Abierta Interamericana, Consejo Nacional de Investigaciones Científicas y Técnicas, CAECIHS.UAI-CONICET, Buenos Aires, Argentina.(2)Centro de Investigaciones en Psicología y Psicopedagogía (CIPP), Facultad de Psicología y Psicopedagogía, Pontificia Universidad Católica Argentina (UCA), Buenos Aires, Argentina.(3)Departmento de Biologia, Facultad de Ciencias de la Salud, Universidad Argentina J F KennedyPerinatal asphyxia (PA) is a neurodevelopmental impairment that leads to neonatal mortality and is a determinant factor for short- and long-term disorders. Since pathophysiological mechanisms triggered by PA are not still totally unveiled, we investigated the changes in the cytoskeleton organization, synapse, and astrocytes in the nervous tissue along the time. For this study, we used a well-established murine model of PA [1]. After one, 2, 4 and 6 months of severe PA (21 min) rats were sacrificed and their brains were analyzed by combining photooxidation, conventional electron microscopy and electron tomography 3-D reconstruction techniques in two areas hypoxia sensible: neostriatum and hippocampus [1]. Findings: Sligthy modifications we observed at at 21 dyas of PA [2]. After one month of PA, we found an increase in the F-actin staining in neostriatal and hippocampal dendritic spines together with some filopodia-likes structures, a typical embryonic type of spines in photooxidated tissue [3] [Fig 1 A). In contrast, after second month of PA, spines were less consistent stained. In addition, we observed an increment of marker for neuronal and glial dysfunction such as GFAP, neurofilament and MAP-2 [3]. These modifications were more clearly defined after 4 months of PA [4]. After 6 months of PA postsynaptic densities (PSDs) in neostriatum were highly modified. Using three-D reconstructions and electron tomography we were able to find clear signs of degeneration in the asphyctic PSDs (Fig 1 B and C) Conclusion & Significance: Therefore, we hypothesize that the cytoskeletal changes induced by PA in the rat CNS could lead to the severe modifications in synapse and related structures that trigger neuronal damage. In addition, electron tomography, 3-D reconstruction and photooxidation contributed to dissect critical alterations generated by PA that are not easily displayed using conventional microscopic techniques. These findings might contribute to generate new therapeutic tools.References1Udovin LD et al (2021). Front Neurosci.13:1345. doi: 10.3389/fnins.2019.01345.2.Herrera MI et al ( 2022 Fron Neurosci https://doi.org/10.3389/fnbeh.2022.9531573- Saraceno GE et al (2016) Exp Neurol. 286:116-123. doi: 10.1016/j.expneurol.2016.08.017. 4--Herrera MI, Kobiec T, Kölliker-Frers R, Otero-Losada M, Capani F (2020. Front Synaptic Neurosci. 23; 12:35. doi: 10.3389/fnsyn.2020.00035.