Parkinson’s disease (PD) is the second most common neurodegenerative disorder characterized by the progressive degeneration of the dopaminergic system, leading to a variety of motor and nonmotor symptoms. The currently available symptomatic therapy loses efficacy over time, indicating the need for new therapeutic approaches. Repetitive transcranial magnetic stimulation (rTMS) has emerged as one of the potential candidates for PD therapy. Intermittent theta burst stimulation (iTBS), an excitatory protocol of rTMS, has been shown to be beneficial in several animal models of neurodegeneration, including PD. The aim of this study was to investigate the effects of prolonged iTBS on motor performance and behavior and the possible association with changes in the NMDAR subunit composition in the 6-hydroxydopamine (6-OHDA)-induced experimental model of PD. Two-month-old male Wistar rats were divided into four groups: controls, 6-OHDA rats, 6-OHDA + iTBS protocol (two times/day/three weeks) and the sham group. The therapeutic effect of iTBS was evaluated by examining motor coordination, balance, spontaneous forelimb use, exploratory behavior, anxiety-like, depressive/anhedonic-like behavior and short-term memory, histopathological changes and changes at the molecular level. We demonstrated the positive effects of iTBS at both motor and behavioral levels. In addition, the beneficial effects were reflected in reduced degeneration of dopaminergic neurons and a subsequent increase in the level of DA in the caudoputamen. Finally, iTBS altered protein expression and NMDAR subunit composition, suggesting a sustained effect. Applied early in the disease course, the iTBS protocol may be a promising candidate for early-stage PD therapy, affecting motor and nonmotor deficits.

Multiple sclerosis (MS) is a chronic neurodegenerative disease caused by autoimmune-mediated inflammation in the central nervous system. Purinergic signaling is critically involved in MS-associated neuroinflammation and its most widely applied animal model—experimental autoimmune encephalomyelitis (EAE). A promising but poorly understood approach in the treatment of MS is repetitive transcranial magnetic stimulation. In the present study, we aimed to investigate the effect of continuous theta-burst stimulation (CTBS), applied over frontal cranial bone, on the adenosine-mediated signaling system in EAE, particularly on CD73/A_2AR/A₁R in the context of neuroinflammatory activation of glial cells. EAE was induced in two-month-old female DA rats and in the disease peak treated with CTBS protocol for ten consecutive days. Lumbosacral spinal cord was analyzed immunohistochemically for adenosine-mediated signaling components and pro- and anti-inflammatory factors. We found downregulated IL-1β and NF- κB-ir and upregulated IL-10 pointing towards a reduction in the neuroinflammatory process in EAE animals after CTBS treatment. Furthermore, CTBS attenuated EAE-induced glial eN/CD73 expression and activity, while inducing a shift in A_2AR expression from glia to neurons, contrary to EAE, where tight coupling of eN/CD73 and A_2AR on glial cells is observed. Finally, increased glial A₁R expression following CTBS supports anti-inflammatory adenosine actions and potentially contributes to the overall neuroprotective effect observed in EAE animals after CTBS treatment.

Chronic benzodiazepine exposure promotes dependence and withdrawal-associated neuroadaptations, yet the underlying neurochemical mechanisms remain insufficiently defined. Here, we examined alterations in dopamine and serotonin levels in the prefrontal cortex (PFC) following alprazolam withdrawal in adult female Wistar rats. Animals received escalating doses of alprazolam over 8 days, followed by abrupt cessation and assessment at 36 h withdrawal time point. Neuromodulator concentrations were quantified using high-performance liquid chromatography (HPLC). Withdrawal induced a significant increase in dopamine levels and a significant decrease in serotonin levels in the PFC. These findings indicate a disruption of neurochemical balance, suggesting that alterations in PFC monoamines may contribute to withdrawal-associated behavioral changes.

Background: Trimethyltin (TMT)-induced neurodegeneration leads to molecular and behavioral changes resembling those of Alzheimer’s disease (AD), making it a relevant model for investigating potential therapeutic interventions. Continuous theta burst stimulation (cTBS) has shown promise in psychiatric and neurological disorders but remains largely unexplored in AD models. Methods: Adult male Wistar rats were divided into four experimental groups: intact, TMT (8 mg/kg, ip) and TMT treated with cTBS or a sham protocol for three weeks. The open field test and novel object recognition test were used to assess anxiety-like behavior, memory, and learning, respectively. The extent of microgliosis in the hippocampus was assessed by immunohistochemistry, while protein expression was estimated by Western blot. Results: cTBS improved TMT-mediated changes in anxiety-like behavior, learning, and memory and reduced microgliosis in the CA1 hippocampal region. Both TMT and cTBS affected NMDAR subunits, with the most significant finding being a cTBS-mediated decrease in NR2B, which was previously increased by TMT. Conclusions: These are the first data on the beneficial effects of cTBS on behavioral and molecular changes in a model of neurodegeneration that mimics some of the key aspects of AD pathology. Further research is needed to clarify the therapeutic potential of cTBS in AD treatment.