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.

Background/Objectives: Benzodiazepine (BZD) withdrawal is frequently associated with altered emotional reactivity and behavior. Given the higher prevalence of anxiety disorders and the more frequent use of BZDs among women, understanding the neurobiology of BZD withdrawal in females is particularly important as it remains elusive. Methods: Adult female Wistar rats received 8 days of chronic, escalating-dose alprazolam (ALP) treatment followed by spontaneous withdrawal assessed at 36 h and 96 h from the last dose. Behavioral assessment was performed using the Open Field Test. Synaptic protein expression was analyzed by Western blot; neurotransmitter and neuromodulator levels were determined using high-performance liquid chromatography (HPLC) and commercial assay kits; and dendritic spine density and morphology were evaluated by Golgi–Cox staining. Results: ALP withdrawal significantly increased levels of anxiety-like behavior while reducing locomotor and exploratory activity. These behavioral changes were accompanied by increased glutamate levels and protein expression of vGluT1, GluR1, NR1, NR2B, and PSD-95, followed by delayed upregulation of EAAT1 and EAAT2. The GABAergic system exhibited heterogeneous remodeling, characterized by increased GAD65, α1-containing GABA_A receptors, and gephyrin, and reduced vGAT expression. Dopamine and serotonin levels remained unchanged, whereas D1 receptor levels were transiently reduced during 36 h withdrawal. The discontinuation of ALP was further associated with temporally selective dendritic spine remodeling, characterized by an early, sustained reduction in branched spine density, a transient increase in filopodia at 36 h, and a reduction in total spine density at 96 h. Conclusions: These findings demonstrate that ALP withdrawal leads to coordinated neurochemical, molecular, and structural remodeling within the amygdala, involving both excitatory and inhibitory synaptic compartments.

Benzodiazepine (BZD) withdrawal is associated with neurochemical adaptations that contribute to withdrawal symptoms; however, monoaminergic alterations within the caudate-putamen (CPu) remain poorly understood. This study investigated dopamine and serotonin concentrations in the CPu following early alprazolam withdrawal in adult female Wistar rats. Animals received an escalating alprazolam treatment regimen (3–9 mg/kg, i.p.) followed by a 36 h withdrawal period. Monoamine concentrations were determined using high-performance liquid chromatography (HPLC). Compared with vehicle-treated animals, the withdrawal group exhibited significantly reduced dopamine and increased serotonin concentrations, suggesting that alprazolam withdrawal disrupts dopaminergic-serotonergic balance within CPu.