Glial cells, including astrocytes and microglia, are pivotal in maintaining central nervous system (CNS) homeostasis and responding to pathological insults. This review elucidates the complex immunomodulatory functions of glial cells, with a particular focus on their involvement in inflammation cascades initiated by the accumulation of alpha-synuclein (α-syn), a hallmark of Parkinson’s disease (PD). Deriving insights from studies on both sporadic and familial forms of PD, as well as animal models of PD, we explore how glial cells contribute to the progression of inflammation triggered by α-syn aggregation. Additionally, we analyze the interplay between glial cells and the blood-brain barrier (BBB), highlighting the role of these cells in maintaining BBB integrity and permeability in the context of PD pathology. Furthermore, we delve into the potential activation of repair and neuroprotective mechanisms mediated by glial cells amidst α-syn-induced neuroinflammation. By integrating information on sporadic and familial PD, as well as BBB dynamics, this review aims to deepen our understanding of the multifaceted interactions between glial cells, α-syn pathology, and CNS inflammation, thereby offering valuable insights into therapeutic strategies for PD and related neurodegenerative disorders.

Deep-brain subthalamic nucleus stimulation (DBS-STN) has become a well-established therapeutic option for advanced Parkinson’s disease (PD). While the motor benefits of DBS-STN are widely acknowledged, the neuropsychiatric effects are still being investigated. Beyond its immediate effects on neuronal circuits, emerging research suggests that DBS-STN might also modulate the peripheral inflammation and neuroinflammation. In this work, we assessed the effects of DBS-STN on food-related motivation, food intake pattern, and the level of anxiety and compared them with markers of cellular and immune activation in nigrostriatal and mesolimbic areas in rats with the 6-OHDA model of early PD. To evaluate the potential mechanism of observed effects, we also measured corticosterone concentration in plasma and leukocyte distribution in peripheral blood. We found that DBS-STN applied during neurodegeneration has beneficial effects on food intake pattern and motivation and reduces anxiety. These behavioral effects occur with reduced percentages of IL-6-labeled cells in the ventral tegmental area and substantia nigra pars compacta in the stimulated brain hemisphere. At the same brain structures, the cFos cell activations were confirmed. Simultaneously, the corticosterone plasma concentration was elevated, and the peripheral blood lymphocytes were reduced after DBS-STN. We believe that comprehending the relationship between the effects of DBS-STN on inflammation and its therapeutic results is essential for optimizing DBS therapy in PD.

Minocycline (MINO), a classic antibiotic, may have psychotropic activity related to the modulation of the tryptophan-kynurenine pathway. In this study, we investigated the effects of MINO on (1) memory and anxiety behaviors, (2) the modulation of brain levels of amyloid precursor protein (APP) and 2,3-indoleamine dioxygenase (IDO1) levels, and (3) peripheral inflammatory markers in a streptozotocin (STZ)-induced rat model of sporadic Alzheimer’s disease (sAD). After repeated treatment with a dose of 35 mg/kg MINO for seven consecutive days, male Wistar rats with sAD showed (1) improvements in early (29 days after injection, probe test) reference memory (decreased latency to reach the platform, increased time in the critical quadrant of the Morris water maze) and anxiety disorders (increased time in the open arms of the elevated plus maze; increased exploration and entrances in the center of the white–light illuminated open field) 45–46 and 90–91 days after STZ injection; (2) reduced APP and IDO1 levels in the hippocampus and prefrontal cortex; and (3) induction of anti-inflammatory response in blood (increased TCD4⁺ lymphocyte number and interleukin-10 production). This suggests that MINO, due to its anti-inflammatory action, improves memory and anxiety behavior related to sAD, indicating its neuroprotective and psychotropic properties.