Lower GDNF Serum Level Is a Possible Risk Factor for Constipation in Patients With Parkinson Disease: A Case–Control Study

Background: Constipation is a significant symptom of Parkinson's disease (PD). Glial-derived neurotrophic factor (GDNF) is important for the morphogenesis of the enteric nervous system and plays a critical role in the preservation of mucosal integrity under enteric glia surveillance. The aim of this work was to evaluate the serum levels of GDNF in patients with PD with and without constipation.Methods: This work included 128 patients with PD. The patients were classified into three groups: those with PD but no constipation (nCons-PD) (n = 49), those with prodromal stage constipation (Cons-Pro-PD) (n = 48), and those with clinical stage constipation (Cons-Clinic-PD) (n = 31). The association between serum GDNF concentration and constipation was explored using logical regression.Results: The nCons-PD group's mean GDNF levels were 528.44 pg/ml, which was higher than the Cons-Pro-PD group's 360.72 pg/ml and the Cons-Clinic-PD group's 331.36 pg/ml. The results of binary logistic regression indicated that GDNF was a protective factor in the prevention of constipation. Cons-Clinic-PD group had a higher score of MDS-UPDRS-II, MDS-UPDRS-III, MDS-UPDRS-IV, and a higher H-Y staging as compared with nCons-PD group. Relative to the nCons-PD group, Cons-Clinic-PD had higher NMSS scores, lower MoCA and PDSS scores, and were more likely to have RBD.Conclusions: GDNF serum levels are lower in patients with PD who are constipated. A low GDNF level is a potential risk factor for constipation in patients with PD.

How Antidepressant Drugs Affect the Antielectroshock Action of Antiseizure Drugs in Mice: A Critical Review

Depression coexists with epilepsy, worsening its course. Treatment of the two diseases enables the possibility of interactions between antidepressant and antiepileptic drugs. The aim of this review was to analyze such interactions in one animal seizure model—the maximal electroshock (MES) in mice. Although numerous antidepressants showed an anticonvulsant action, mianserin exhibited a proconvulsant effect against electroconvulsions. In most cases, antidepressants potentiated or remained ineffective in relation to the antielectroshock action of classical antiepileptic drugs. However, mianserin and trazodone reduced the action of valproate, phenytoin, and carbamazepine against the MES test. Antiseizure drug effects were potentiated by all groups of antidepressants independently of their mechanisms of action. Therefore, other factors, including brain-derived neurotrophic factor (BDNF) and glial-derived neurotrophic factor (GDNF) modulation, should be considered as the background for the effect of drug combinations.

Expression of Selected Genes Involved in Neurogenesis in the Etiopathogenesis of Depressive Disorders

(1) Background: The neurogenic theory suggests that impaired neurogenesis within the dentate gyrus of the hippocampus is one of the factors causing depression. Immunology also has an impact on neurotrophic factors. The aim of the study was to assess the importance of selected genes involved in the process of neurogenesis i.e., nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), glial-derived neurotrophic factor (GDNF) and neuron-restrictive silencer factor (REST gene) in the etiopathogenesis of depressive disorders. (2) Methods: A total of 189 subjects took part in the study (95 depressed patients, 94 healthy controls). Sociodemographic data were collected. The severity of depressive symptoms was assessed using the Hamilton Depression Rating Scale (HDRS). RT-PCR was used to assess gene expression at the mRNA levels, while Enzyme-Linked Immunosorbent Assay (ELISA) was used to assess gene expression at the protein level. (3) Results: Expression of NGF, BDNF, REST genes is lower in depressed patients than in the control group, whereas the expression of GDNF gene is higher in patients with depressive disorders than in the group of healthy volunteers. (4) Conclusions: The expression of selected genes might serve as a biomarker of depression.

Macrophage-Derived Inflammation Induces a Transcriptome Makeover in Mesenchymal Stromal Cells Enhancing Their Potential for Tissue Repair

Pre-clinical and clinical studies revealed that mesenchymal stromal cell (MSC) transplants elicit tissue repair. Conditioning MSC prior to transplantation may boost their ability to support repair. We investigated macrophage-derived inflammation as a means to condition MSC by comprehensively analyzing their transcriptome and secretome. Conditioning MSC with macrophage-derived inflammation resulted in 3208 differentially expressed genes, which were annotated with significantly enriched GO terms for 1085 biological processes, 85 cellular components, and 79 molecular functions. Inflammation-mediated conditioning increased the secretion of growth factors that are key for tissue repair, including vascular endothelial growth factor, hepatocyte growth factor, nerve growth factor and glial-derived neurotrophic factor. Furthermore, we found that inflammation-mediated conditioning induces transcriptomic changes that challenge the viability and mobility of MSC. Our data support the notion that macrophage-derived inflammation stimulates MSC to augment their paracrine repair-supporting activity. The results suggest that inflammatory pre-conditioning enhances the therapeutic potential of MSC transplants.