Alzheimer’s disease (AD) is characterized by impaired neurotrophic support, oxidative stress, and metabolic dysfunction. Using the intracerebroventricular streptozotocin (ICV-STZ) rat model of sporadic AD, we investigated whether vitamin D3 (VitD3) and dimethyl fumarate (DMF), administered alone or in combination, modulate hippocampal neurotrophin-related signaling and redox balance. Animals were assigned to SHAM, STZ, VITD, DMF, and COMBO groups, representing control, ICV-STZ, VitD3-treated ICV-STZ, DMF-treated ICV-STZ, and combined VitD3 + DMF-treated ICV-STZ animals, respectively. Hippocampal neurotrophin processing (proBDNF and mature BDNF), downstream signaling (Akt and pAkt), IGF-1 content, mitochondrial oxoglutarate dehydrogenase (OGDH) content, citrate synthase (CS) activity, and glutathione peroxidase (GPx) activity were assessed. STZ administration showed a trend toward reduced mature BDNF content compared with the SHAM group (p = 0.07), whereas combined VitD3 and DMF treatment significantly increased mature BDNF content compared with the STZ group. The mature BDNF/proBDNF ratio was reduced in the STZ group compared with the SHAM group and tended to be higher in the COMBO group compared with the STZ group (p = 0.09). proBDNF content remained unchanged. IGF-1, pTrkB, total Akt, and pAkt content did not differ significantly between groups. The pAkt/Akt ratio showed a trend toward reduction in the STZ group compared with SHAM group (p = 0.09). GPx activity increased in the STZ group, while CS activity and OGDH content were not significantly altered. These findings indicate that STZ-induced neurodegeneration is characterized by redox-associated uncoupling of neurotrophic signaling rather than mitochondrial disruption. Combined VitD3 and DMF treatment partially modulated neurotrophic signaling, supporting a limited but measurable neuroprotective effect.
Piekarczyk et al. (Fri,) studied this question.