Daria Korewo-Labelle

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.

Chronic cold exposure is a stressor that may adversely affect the hippocampal structure and cognitive function. Critical for memory formation and learning processes, the hippocampus is particularly susceptible to hypothalamic–pituitary–adrenal (HPA) axis activity and elevated glucocorticoid levels. Vitamin D plays a complex role in regulating mitochondrial function and may provide neuroprotection. This study aimed to investigate the effects of chronic cold exposure on proteins associated with signaling pathways, mitochondrial function, and oxidative stress in the hippocampus of rats and to evaluate the neuroprotective potential of vitamin D3 supplementation. Male Wistar rats (n = 26) were assigned to four groups: control (CON; n = 4), sham stress (WW; n = 6), chronic cold water immersion (CCWI) (CW group; n = 8), and CCWI with 600 IU/kg/day vitamin D3 (VD3) supplementation (CW + D group; n = 8). Exposure to CCWI significantly reduced the hippocampal mass of rats, an effect not reversed by vitamin D3 supplementation. However, vitamin D3 improved mitochondrial function and exhibited antioxidant effects, partially reducing markers of protein and lipid free radicals damage in neural tissue. Our findings demonstrate the antioxidant properties of VD3 and its potential role in mitigating hippocampal damage during prolonged cold exposure, although its neuroprotective effects remain limited.

This review offers a comprehensive evaluation of current aspects related to nutritional strategies, brain modulation, and muscle recovery, focusing on their applications and the underlying mechanisms of physiological adaptation for promoting a healthy brain, not only in athletes but also for recreationally active and inactive individuals. We propose that applying the rule, among others, of good sleep, regular exercise, and a properly balanced diet, defined as “SPARKS”, will have a beneficial effect on the function and regeneration processes of the gut–brain–muscle axis. However, adopting the formula, among others, of poor sleep, stress, overtraining, and dysbiosis, defined as “SMOULDER”, will have a detrimental impact on the function of this axis and consequently on human health as well as on athletes. Understanding these dynamics is crucial for optimizing brain health and cognitive function. This review highlights the significance of these factors for overall well-being, suggesting that adopting the “SPARKS” approach may benefit not only athletes but also older adults and individuals with health conditions.

Dexamethasone (DEXA) is a commonly used steroid drug with immunosuppressive and analgesic properties. Unfortunately, long-term exposure to DEXA severely impairs brain function. This study aimed to investigate the effects of vitamin D₃ supplementation during chronic DEXA treatment on neurogenesis, mitochondrial energy metabolism, protein levels involved in the BDNF-mediated Akt activity, and specific receptors in the hippocampus. We found reduced serum concentrations of 25-hydroxyvitamin D₃ (25(OH)D₃), downregulated proBDNF and pAkt, dysregulated glucocorticosteroid and mineralocorticoid receptors, impaired mitochondrial biogenesis, and dysfunctional mitochondria energy metabolism in the DEXA-treated group. In contrast, supplementation with vitamin D₃ restored the 25(OH)D₃ concentration to a value close to that of the control group. There was an elevation in neurotrophic factor protein level, along with augmented activity of pAkt and increased citrate synthase activity in the hippocampus after vitamin D₃ administration in long-term DEXA-treated rats. Our findings demonstrate that vitamin D₃ supplementation plays a protective role in the hippocampus and partially mitigates the deleterious effects of long-term DEXA administration. The association between serum 25(OH)D₃ concentration and BDNF level in the hippocampus indicates the importance of applying vitamin D₃ supplementation to prevent and treat pathological conditions.

The current study aimed to investigate whether a 12-week Body Mass Index (BMI)-based (the higher the BMI, the higher the dosage) vitamin D₃ administration may affect both the kynurenine pathway (KP) and the inflammatory state in Parkinson’s disease (PD) patients with deep brain stimulation (DBS) and may be useful for developing novel therapeutic targets against PD. Patients were randomly assigned to two groups: supplemented with vitamin D₃ (VitD, n = 15) and treated with vegetable oil (PL, n = 21). Administration lasted for 12 weeks. The isotope dilution method by LC-MS/MS was applied to measure KP and vitamin D metabolites. Serum concentrations of cytokines such as IL-6 and TNF-α were measured using ELISA kits. After administration, the serum concentration of TNF-α decreased in PD patients with DBS. Moreover, in KP: 3-hydroksykynurenine (3-HK) was increased in the PL group, picolinic acid was decreased in the PL group, and kynurenic acid tended to be higher after administration. Furthermore, a negative correlation between 3-HK and 25(OH)D₃ and 24,25(OH)₂D₃ was noticed. Our preliminary results provide further evidence regarding a key link between the KP substances, inflammation status, and metabolites of vitamin D in PD patients with DBS. These findings may reflect the neuroprotective abilities of vitamin D₃ in PD patients with DBS.

Parkinson’s disease (PD) is the second most common neurodegenerative disease. To manage motor symptoms not controlled adequately with medication, deep brain stimulation (DBS) is used. PD patients often manifest vitamin D deficiency, which may be connected with a higher risk of falls. We administered a 12-week vitamin D₃ supplementation based on BMI (with higher doses given to patients with higher BMI) to investigate its effects on physical performance and inflammation status in PD patients with DBS. Patients were randomly divided into two groups: treated with vitamin D₃ (VitD, n = 13), and supplemented with vegetable oil as the placebo group (PL, n = 16). Patients underwent functional tests to assess their physical performance three times during this study. The serum 25(OH)D₃ concentration increased to the recommended level of 30 ng/mL in the VitD group, and a significant elevation in vitamin D metabolites in this group was found. We observed significant improvement in the Up and Go and the 6 MWT in the VitD group. In inflammation status, we noticed a trend toward a decrease in the VitD group. To conclude, achieving the optimal serum 25(OH)D₃ concentration is associated with better functional test performance and consequently may have a positive impact on reducing falling risk in PD.

Elderberry fruits contain valuable components that are beneficial to human health. Owing to the high content of anthocyanins, elderberry extracts can be used as natural food colorants with health-promoting properties. Moreover, the development of new natural food dyes enables the reduction in the use of synthetic ones. Anthocyanins-rich elderberry dry extracts (EDE) were prepared from the same batch of frozen fruits applying water extraction, followed by membrane separation (batch B1) or purification by column chromatography (batch B2) and then spray-dried. Subsequently, the content of anthocyanins, flavonols, and polyphenols was determined. The extract obtained with the application of column chromatography (B2) contained 33% anthocyanins, which is more than typical market standards, whereas the extract B1 contained 14% anthocyanins. The color properties of both extracts were also determined. Since water was used as an extractant, the extracts are well soluble in water and can therefore be used as a natural food colorant. The cytotoxic activity of both extracts was additionally determined using the MTT test and the tumor cells of the A-549, A-2780, MCF-7, Caco-2 line, and Peripheral blood mononuclear cells. It was revealed that both EDEs inhibit the proliferation of cancer cells, except those of the lung cancers. Extract B2 showed a much stronger cytotoxic effect. Additionally, both extracts stimulate the proliferation of peripheral blood mononuclear cells since they may have immunostimulatory properties.

(1) The study aimed to investigate whether vitamin D₃ supplementation would positively affect rats with glucocorticoids-induced muscle atrophy as measured by skeletal muscle mass in two experimental conditions: chronic dexamethasone (DEX) administration and a model of the chronic stress response. (2) The study lasted 28 consecutive days and was performed on 45 male Wistar rats randomly divided into six groups. These included two groups treated by abdominal injection of DEX at a dose of 2 mg/kg/day supplemented with vegetable oil (DEX PL; n = 7) or with vitamin D₃ 600 IU/kg/day (DEX SUP; n = 8), respectively, and a control group treated with an abdominal injection of saline (CON; n = 6). In addition, there were two groups of rats chronically stressed by cold water immersion (1 hour/day in a glass box with 1-cm-deep ice/water mixture; temperature ~4 °C), which were supplemented with vegetable oil as a placebo (STR PL; n = 9) or vitamin D₃ at 600 IU/kg/day (STR SUP; n = 9). The last group was of sham-stressed rats (SHM; n = 6). Blood, soleus, extensor digitorum longus, gastrocnemius, tibialis anterior, and quadriceps femoris muscles were collected and weighed. The heart, liver, spleen, and thymus were removed and weighed immediately after sacrifice. The plasma corticosterone (CORT) and vitamin D₃ metabolites were measured. (3) We found elevated CORT levels in both cold water-immersed groups; however, they did not alter body and muscle weight. Body weight and muscle loss occurred in groups with exogenously administered DEX, with the exception of the soleus muscle in rats supplemented with vitamin D₃. Decreased serum 25(OH)D₃ concentrations in DEX-treated rats were observed, and the cold water immersion did not affect vitamin D₃ levels. (4) Our results indicate that DEX-induced muscle loss was abolished in rats supplemented with vitamin D₃, especially in the soleus muscle.