SPINAL CORD INJURY DRIVES CHRONIC HIPPOCAMPAL CHANGES

IGNACIO JURE; FLORENCIA LABOMBARDA; ALEJANDRO F. DE NICOLA; JUAN MANUEL ENCINAS

Mar del Plata

Congreso; Reunion Anual de Sociedades de Biociencia 2019; 2019

Sociedad Argentinad e Investigacion Clinica

Abstract/Resumen: After spinal cord injury (SCI), patientsexhibit cognitive deficits that could be related to hippocampalalterations. The objectives of this work were:1) to determinewhich step in the neurogenic process was altered after chronicSCI; 2) to explore the role of acute glucocorticoids (GC) andtransneuronal degeneration in chronic neurogenesis reductionafter SCI; 3) To evaluate cognitive hippocampal dependent-tasksafter chronic SCI. In order to perform the first objective, we usedNestin-GFP mice combined with multiple immunolabeling (BrdU,GFAP, doublecortin DCX) and confocal microscopy. Survival andmitotic capability of neural stem cells (NSCs, Nestin-GFP+/GFAP+) and amplifying progenitors (ANP, Nestin-GFP+/GFAP-) were assessed by labeling these cells with BrdU.The number of DCX + cells together with mitotic NSCs and ANPswas downregulated after 60 days post-injury (dpi) (p<0.05, SCIvs. sham). To comply with the second objective, GC action wasblocked using the GC receptor antagonist, RU-486 during theacute phase and neurogenesis was measured 60dpi. This resultimplied acute GC in chronic neurogenesis reduction since thenumber of DCX + cells was restored after RU-486-treatment(p<0.01, SCI vs. SCI+RU486). On the other hand, spinal cordhemisection was performed in order to lacerate axons of only oneside. Afterwards, neurogenesis 60 dpi was measured in theipsilateral and contralateral hippocampus. Neurogenesisdecreased in the contralateral side with respect to the ipsilateralside (p<0.05), which would involve transneuronal degenerationin this downregulation. To achieve the last objective, cognitivehippocampal dependent-tasks were evaluated using the novelobject recognition and Y-maze test. After SCI, animals showeddeficits in recognition (p<0.01, SCI vs. Sham) and spatialworking memory (p<0.01, SCI vs. sham) 60 dpi. These resultssupport that acute GC and transneuronal degeneration causedchronic neurogenesis reduction that could lead to cognitiveimpairments