Systemic Thymulin gene therapy reverses memory and behavioral impairments and reduces neuroinflammation in a rat model of sporadic Alzheimer’s disease

ANA ABRIL VIDAL ESCOBEDO; JULIETTE LÓPEZ HANOTTE; FACUNDO PERALTA; JULIA DIAZ BALEIRO; MARIA FLORENCIA ZAPPA VILLAR; JOAQUIN PARDO; PAULA CECILIA REGGIANI

San Luis

Congreso; SAN 2023; 2023

Sociedad Argentina de Neurociencias (SAN)

To investigate Sporadic Alzheimer’s disease (sAD) therapies, we used an sAD model in rats based on a single intracerebroventricular (icv) streptozotocin (STZ) injection, resulting in increased hippocampal microglia and astrocytes 3 months after icv-STZ administration. Thymulin (FTS), a thymic peptide, has demonstrated anti-inflammatory effects. We employed an adenoviral vector (RAd-FTS) for systemic overexpression of FTS through intramuscular (IM) injections. Rats were divided into 3 groups: SHAM, STZ, and FTS. Animals received bilateral icv injections of artificial cerebrospinal fluid (SHAM) or STZ (STZ and FTS groups) (3mg/kg). At weeks 1 and 6 post STZ, FTS animals received IM injections of RAd-FTS. Before sacrifices (13 week), we are performed behavioral tests to evaluate species-typical, exploratory, anxiety and depressive-like behaviors, and recognition memory. Through immunohistochemistry experiments, we assessed immature neurons and microglia in the hippocampus. STZ-treated animals exhibited impaired exploratory activity, and recognition memory. However, FTS group showed no significant differences compared to the SHAM group in all evaluated behaviors. Although FTS did not recover immature neurons affected by STZ, it did have a central anti-inflammatory effect by reducing microglial reactivity. Therefore, systemic thymulin overexpression effectively reversed altered behavioral changes caused by STZ, and had an anti-inflammatory impact in the sAD rat model.