IGF-1 GENE THERAPY REVERSES HIPPOCAMPAL ALTERATIONS AFTER SPINAL CORD INJURY

IGNACIO JURE; MARIA JOSE BELLINI; CONSTANZA SPOTORNO; ALEJANDRO F. DE NICOLA; EUGENIA FALOMIR; FLORENCIA LABOMBARDA

Mar del Plata

Congreso; Reunion Anual de Sociedades de Biociencia 2019; 2019

Sociedad Argentina de Investigacion Clinica

Abstract/Resumen: After spinal cord injury (SCI), patients exhibit cognitive deficits that could be related to hippocampal alterations. We have previously described hippocampal neuroinflammation, neurogenesis reduction and cognitive impairments in rats after chronic SCI. Since insulin-like growth factor 1 (IGF-1) enhances neurogenesis and IGF1 gene therapy modifies the inflammatory response and ameliorates cognitive impairments in other models, we decided to evaluate whether an adenoviral vector expressing IGF-1 could reverse hippocampal alterations and cognitive deficits observed in rats after SCI. Sixty days post-injury (dpi), rats were injected in the lateral ventricles with a recombinant adenoviral constructed harboring the cDNA of rat IGF-1 as a therapeutic virus 1 (RAd-IGF-1) or the cDNA of red fluorescent protein, as a control virus (RAd-DsRed) or saline solution. Neurogenesis and cognitive hippocampal dependenttasks were evaluated 15 dpi. As expected, the number of neuroblasts (doublecortin + cells) decreased after chronic SCI (p<0.01, SCI vs. sham). After the treatment with RAd-IGF1, neurogenesis increased in lesioned rats (p<0.05, SCI+RAdDsRed control vs. SCI+Rad-IGF-1). Regarding cognitive performance, recognition and spatial working memory were assayed 60 dpi using the novel object recognition and Y-maze test respectively. The discrimination index decreased 24 h after the familiarization phase in the lesioned group (p<0.001 SCI vs Sham), while IGF-1 treatment increased the mentioned index in lesioned rats (p<0.05, SCI+RAd-DsRed vs. SCI+RAd-IGF-1). The percentage of spontaneous alternations decreased in lesionedrats (p<0.01 SCI vs Sham) while injured rats treated with the adenoviral IGF-1 injection increased the percentage of spontaneous alternation (p<0.05, SCI+RAd-DsRed vs. SCI+RAdIGF-1). These results support that therapies which enhance endogenous IGF-1 expression might be a possible treatment for the encephalopathy developed by SCI.