Isolation of a CD8alphaalpha+ CD4- tumour T-cell clone with cytotoxic activity from a CD4+ CD8- cutaneous T-cell lymphoma.

UNLABELLED: Fingolimod, a sphingosine-1-phosphate (S1P) receptor modulator, has demonstrated neuroprotective and anti-inflammatory effects in experimental models of neurodegenerative diseases; however, its optimal therapeutic dose for Alzheimer's disease-like cognitive impairment remains unclear. This study investigated the dose-dependent effects of fingolimod on cognition, neuroinflammation, oxidative stress, neurotrophic factor expression, and hippocampal stereological changes in a rat model of streptozotocin (STZ)-induced memory impairment. Male Sprague-Dawley rats were assigned to control, STZ (3 mg/kg, intracerebroventricular), and STZ plus fingolimod (0.25, 0.5, or 1 mg/kg/day, intraperitoneal) groups. Behavioral performance was evaluated using the open-field, Morris water maze, and passive avoidance tests. Hippocampal expression of brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) was quantified by quantitative reverse-transcription polymerase chain reaction. Lipid peroxidation and hippocampal structural changes were assessed by malondialdehyde (MDA) measurement and stereological analysis, respectively. STZ induced cognitive impairment, increased hippocampal expression of pro-inflammatory cytokines, elevated MDA levels, and reduced CA1 neuronal number and volume. Fingolimod (0.25 mg/kg) improved spatial and fear- related memory performance while reducing neuroinflammatory and oxidative stress markers. The 0.5 mg/kg dose provided the greatest preservation of CA1 neuronal number and total volume. Animals receiving 1 mg/kg exhibited poor tolerability and were excluded. Fingolimod exerted dose-dependent, domain-specific effects, with lower doses improving functional outcomes and the intermediate dose providing greater preservation of hippocampal structure. These findings suggest beneficial effects within the doses examined, although additional dose-response studies are needed to determine the optimal therapeutic range.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13205-026-05015-3.