Background: Paroxetine, a selective serotonin reuptake inhibitor for counteracting depression, has been recently suggested as having a role in prevention of dopaminergic neuronal degeneration in substantia nigra, a hallmark of Parkinson's disease (PD). The pathogenesis of this type of neurological disorders often involves the activation of microglia and associated inflammatory processes. Thus in this study we aimed to understand the role of paroxetine in microglia activation and to elucidate the underlying mechanism(s). Methods: BV2 and primary microglial cells were pretreated with paroxetine and stimulated with lipopolysaccharide (LPS). Cells were assessed for the responses of pro-inflammatory mediator and cytokines, and the related signaling pathways were evaluated and analyzed in BV2 cells. Results: Paroxetine significantly inhibited LPS-induced production of nitric oxide (NO) and pro-inflammatory cytokines such as TNF-α and IL-1β. Further analysis showed inducible nitric oxide synthase (iNOS) and mRNA expression of TNF-α and IL-1β were attenuated by paroxetine pretreatment. Analyses in signaling pathways demonstrated that paroxetine led to suppression of LPS-induced JNK1/2 activation and baseline ERK1/2 activity, but had little effect on the activation of p38 and p65/NF-κB. Interference with specific inhibitors revealed that paroxetine-mediated suppression of NO production was via JNK1/2 pathway while the cytokine suppression was via both JNK1/2 and ERK1/2 pathways. Furthermore, conditioned media culture showed that paroxetine suppressed the microglia-mediated neurotoxicity.

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Nitrogen-enriched porous carbon fibers were successfully prepared by one-step carbonization–activation treatment of oxidized polyacrylonitrile fibers. Utilizing the low-temperature carbonization and air activation, lots of narrow micropores were developed, and the volume of pores with a size below 0.8 nm was in the range of 0.110–0.122 g/cm3. Meanwhile, nitrogen preserved in the fibers exceeded 20.8 wt % in content. The porous carbon fiber exhibited an optimal CO2 uptake of 99 mg/g at 25 °C and 1 bar. More importantly, an incomparable Henry’s law CO2/N2 selectivity of 183 was achieved, which was primarily attributed to the prominent nitrogen-containing functionalities. Additionally, the sample had a low isosteric heat of adsorption, between 26.65 and 30.84 kJ/mol. This work provides a convenient strategy for the construction of CO2 adsorbent with high selectivity from nitrogen-containing starting materials.

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Introduction: Autonomic dysfunction is a common and disabling non-motor symptom of Parkinson's disease (PD). We aimed to understand autonomic dysfunction in PD motor subtypes, the pattern of sympathetic skin response (SSR) to motor asymmetry, and the association of SSR with autonomic and motor dysfunctions. Methods: A total of 101 PD patients of Han Chinese were included. Unified PD rating scale (UPDRS), scales for outcomes in PD-autonomic symptoms (SCOPA-AUT), orthostatic hypotension, and SSR were evaluated. Results: SCOPA-AUT and incidences of orthostatic hypotension and absent SSR were worse in the subtype of postural instability gait disorder (PIGD) than the subtypes of tremor dominant and intermediate. SSR latency and amplitude were asymmetrical corresponding to the accentuation of motor severity. Patients with absent SSR had worse UPDRS and SCOPA-AUT scores. SSR parameters of the severe side in patients with SSR showed no independent association with the scores. Conclusion: Our results support that autonomic dysfunction is more severe in the PIGD than other subtypes and demonstrate an asymmetry of SSR in PD patients. Absent SSR may indicate worse autonomic and motor symptoms, but SSR parameters are not sufficient to evaluate the severity of the dysfunctions.

Background Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) are commonly used new-generation drugs for depression. Depressive symptoms are thought to be closely related to neuroinflammation. In this study, we used up-to-date protocols of culture and stimulation and aimed to understand how astrocytes respond to the antidepressants. Methods Primary astrocytes were isolated and cultured using neurobasal-based serum-free medium. The cells were treated with a cytokine mixture comprising complement component 1q, tumor necrosis factor α, and interleukin 1α with or without pretreatments of antidepressants. Cell viability, phenotypes, inflammatory responses, and the underlying mechanisms were analyzed. Results All the SSRIs, including paroxetine, fluoxetine, sertraline, citalopram, and fluvoxamine, show a visible cytotoxicity within the range of applied doses, and a paradoxical effect on astrocytic inflammatory responses as manifested by the promotion of inducible nitric oxide synthase (iNOS) and/or nitric oxide (NO) and the inhibition of interleukin 6 (IL-6) and/or interleukin 1β (IL-1β). The SNRI venlafaxine was the least toxic to astrocytes and inhibited the production of IL-6 and IL-1β but with no impact on iNOS and NO. All the drugs had no regulation on the polarization of astrocytic A1 and A2 types. Mechanisms associated with the antidepressants in astrocytic inflammation route via inhibition of JNK1 activation and STAT3 basal activity. Conclusions The study demonstrated that the antidepressants possess differential cytotoxicity to astrocytes and function differently, also paradoxically for the SSRIs, to astrocytic inflammation. Our results provide novel pieces into understanding the differential efficacy and tolerability of the antidepressants in treating patients in the context of astrocytes.

Parkinsonism-hyperpyrexia syndrome (PHS) and dyskinesia-hyperpyrexia syndrome (DHS) are rare but exhibit life-threatening complications in Parkinson’s disease (PD). We herein presented two cases of PD patients and performed a comprehensive and comparative literature review for these two syndromes. The first case was diagnosed as PHS with cerebral salt wasting syndrome caused by abrupt withdrawal of antiparkinsonian medication. Her symptoms were gradually remitted with reinstitution of the medication. The second one was an early-stage PD patient diagnosed as DHS in association with abuse of antiparkinsonian drugs. Her symptoms were gradually remitted with reduced dosage of dopaminergic drugs. Results of literature reviews revealed a total of 56 and 13 cases of PHS and DHS, respectively, and they were more likely to occur in elderly and long-term PD patients. These two syndromes showed different female-to-male ratio, similar mortality, and different recovery time. There were stark differences between PHS and DHS, including triggers (abrupt drug stoppage versus drug abuse), symptoms (worsened tremor and rigidity versus continuous dyskinesia), and treatment (drug reinstitution versus drug reduction). In summary, our reports and the review provide new insights into PHS and DHS in association with PD and may facilitate rapid discrimination of the syndromes for timely and proper treatment to reduce mortality.

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