The disorder of adult neurogenesis is considered an important mechanism underlying the learning and memory impairment observed in Alzheimer’s disease (AD). The sporadic nonhereditary form of AD (sAD) affects over 95% of AD patients and is related to interactions between genetic and environmental factors. An intracerebroventricular injection of streptozotocin (STZ-ICV) is a representative and well-established method to induce sAD-like pathology. Dimethyl fumarate (DMF) has antioxidant and anti-inflammatory properties and is used for multiple sclerosis treatment. The present study determines whether a 26-day DMF therapy ameliorates the disruption of adult neurogenesis and BDNF-related neuroprotection in the hippocampus and olfactory bulb (OB) in an STZ-ICV rat model of sAD. Considering age as an important risk factor for developing AD, this study was performed using 3-month-old (the young group) and 22-month-old (the aged group) male Wistar rats. Spatial cognitive functions were evaluated with the Morris water maze task. Immunofluorescent labelling was used to assess the parameters of adult neurogenesis and BDNF-related neuroprotection in the hippocampus and OB. Our results showed that the STZ-ICV evoked spatial learning and memory impairment and disturbances in adult neurogenesis and BDNF expression in both examined brain structures. In the aged animals, the deficits were more severe. We found that the DMF treatment significantly alleviated STZ-ICV-induced behavioural and neuronal disorders in both age groups of the rats. Our findings suggest that DMF, due to its beneficial effect on the formation of new neurons and BDNF-related neuroprotection, may be considered as a promising new therapeutic agent in human sAD.

The amygdala, especially its central nucleus (CeA), is one of the key brain structures regulating fear, anxiety and stress responses and is also involved in gut microbiota signal processing. Amygdala hyperactivity, as well as microbiota alterations, plays an important role in the pathophysiology of anxiety disorders, depression or post-traumatic stress disorder (PTSD). The present study determines whether 3 weeks of galactooligosaccharide (GOS) supplementation alleviates behavioural, haematological, immunological and gut microbiota disturbances induced by long-term electrical stimulation of the CeA in rats (Stim). The unsupplemented Stim group showed locomotor hyperactivity and higher anxiety (measured with an actometer and the elevated plus maze, respectively), as well as a decrease in white blood cells (WBCs), lymphocytes (LYMs), red blood cells (RBCs) and platelets (PLTs); an elevation of TNFα; a reduction in IL-10 concentration in plasma; and microbiota alterations as compared to the control (Sham) group. GOS supplementation alleviated all these Stim-induced adverse effects or even normalised them to the sham group level. The effect of GOS was comparable to citalopram and even more effective in WBC and PLT normalisation and IL-10 induction. The obtained results indicate the high therapeutic potential of GOS in anxiety and stress-related disorders. GOS supplementation may support conventional therapy or the prevention of PTSD, depression and anxiety disorders.

Non-motor symptoms of PD impair quality of life and remain challenging to treat. Here, we examined the effects of short- (38 days) and long-term (178 days) supplementation with the natural polyamine spermidine on anhedonia and anxiety-like behaviours in a 6-hydroxydopamine-induced rat model of PD and linked them with spermidine’s anti-inflammatory properties. Behavioural assessments (cylinder, sucrose preference, elevated plus-maze tests) were conducted during progressive neurodegeneration and after oral treatment. Under the same conditions, peripheral inflammation was evaluated by the total leukocytes and their subpopulation numbers (hematological analysis) and by CD4⁺ and CD8⁺ T lymphocyte percentages (imaging flow cytometry); the plasma levels of interleukins 4 and 10 and corticosterone (enzyme-linked immunosorbent assay) were also evaluated. The safety of long-term supplementation was assessed using standard biochemical markers (chemistry analyser). Both treatment regimens reversed 6-hydroxydopamine-induced lymphopenia. Long-term spermidine treatment increased the number of TCD4⁺ lymphocytes and monocytes and elevated the plasma concentrations of IL-4 and IL-10, while reducing corticosterone levels. These immunomodulatory effects were associated with reduced anhedonia and anxiety. All of the biochemical safety parameters remained within normal ranges. Spermidine alleviates neuropsychiatric symptoms in a rat model of progressive neurodegeneration in the nigrostriatal system through its regulatory influence on peripheral immune responses. Exploring the systemic mechanisms underlying spermidine’s effects could unveil innovative supplementation strategies and expand treatment options for managing symptoms in PD.