Sessions

As life expectancy continues to increase, age-related neurodegenerative disorders such as Alzheimer’s disease pose an ever-growing challenge to society and healthcare systems. Alzheimer’s disease is one of the most prevalent neurodegenerative disorders and is characterized primarily by progressive memory impairment and cognitive decline. Its pathogenesis is multifactorial: in addition to the pathological accumulation of amyloid-β and tau proteins, synaptic loss, mitochondrial dysfunction, and reactive glial alterations all contribute to the characteristic neuropathological changes. Autophagy represents an important protective mechanism against these processes; however, its activity gradually declines with aging.

Spermidine is an endogenous polyamine that is considered a caloric restriction mimetic. Through its ability to stimulate autophagy and reduce oxidative stress, spermidine may exert neuroprotective effects and has therefore emerged as a promising candidate for the treatment of Alzheimer’s disease. In the present study, we investigated the ultrastructural effects of spermidine treatment on neural tissue using quantitative electron microscopy, with particular emphasis on synapses, mitochondria, and glial cell morphology. Fixed brain tissue samples from 3xTg-AD mice and age-matched control animals were analyzed.

In the hippocampus, spermidine treatment induced a shift of several ultrastructural parameters toward control values, including postsynaptic density (PSD) length and mitochondrial density. In addition, alterations in the organization of the glial compartment were observed, reflected by an increased proportion of neuropil occupied by glial processes. In contrast, the cerebellum exhibited a more limited response to treatment: most synaptic and mitochondrial parameters remained largely unchanged, whereas glial morphological features showed trends suggestive of partial normalization.

Our findings indicate that spermidine induces modest but measurable ultrastructural changes in the 3xTg-AD mouse model. These effects were most prominent in the hippocampus, where synaptic, mitochondrial and glial parameters were all affected by treatment. The results suggest that the neuroprotective actions of spermidine may be region-specific and may contribute to the partial preservation of neuropil structural integrity in Alzheimer's disease.