Water-avoidance stress aggravates prostatic inflammation in a murine model of chronic prostatitis.

OBJECTIVES: To date, few studies have considered the influence of psychological factors on chronic prostatitis (PRO) models. Here, we aimed to refine a murine PRO model combining chemically induced prostatitis with psychological stress. METHODS: A total of 40 mice were randomly divided into four groups: normal control (NC) group, PRO group, water avoidance stress (WAS) group, and PRO + WAS group. Ten mice were assigned to each group: five for cystometrograms (CMGs) and five for von Frey testing and histological analysis. PRO was induced through a prostatic injection of 10% paraformaldehyde. The WAS mice were placed on the middle platform for 1 h per day for 10 consecutive days. RESULTS: The results of the von Frey test demonstrated that both WAS and PRO induced bladder hyperalgesia in mice, and the WAS + PRO group showed significant pelvic pain symptoms either. The CMG results suggested that the PRO group, the WAS group, and the PRO + WAS group all exhibited bladder overactivity, presented as a shortened micturition interval and decreased threshold pressure evoking bladder contraction. The symptoms of the PRO group and the PRO + WAS group were more severe than those of the WAS group. The tissue staining results indicated that WAS itself caused only mild prostatic inflammation but could significantly aggravate chemical-induced prostatic inflammation, as well as the total number of mast cells and proportion of activated mast cells. CONCLUSIONS: Our refined murine PRO model could manifest persistent bladder overactivity, pelvic hyperalgesia and prostatic inflammation. WAS could induce mild prostatic inflammation and aggravate primary prostatic inflammation.

The rapid change in mental health among college students after introduction of on-campus quarantine during the 2022 Shanghai COVID-19 lockdown.

Objectives: Among the various impacts of disasters in terms of emotions, quarantine has been proven to result in significant increases in mental health problems. Studies of psychological resilience during outbreaks of epidemics tend to focus on long-term social quarantine. In contrast, insufficient studies have been conducted examining how rapidly negative mental health outcomes occur and how these outcomes change over time. We evaluated the time course of psychological resilience (over three different phases of quarantine) among students at Shanghai Jiao Tong University to investigate the influence of unexpected changes on college students. Methods: An online survey was conducted from 5 to 7 April 2022. A structured online questionnaire was administered using a retrospective cohort trial design. Before 9 March (Period 1), individuals engaged in their usual activities without restrictions. From 9 to 23 March (Period 2), the majority of students were asked to remain in their dormitories on campus. From 24 March to early April (Period 3), restrictions were relaxed, and students were gradually allowed to participate in essential activities on campus. We quantified dynamic changes in the severity of students' depressive symptoms over the course of these three periods. The survey consisted of five sets of self-reported questions: demographic information, lifestyle/activity restrictions, a brief mental health history, COVID-19-related background, and the Beck Depression Inventory, second edition. Results: A total of 274 college students aged 18-42 years (mean = 22.34; SE = 0.24) participated in the study (58.39% undergraduate students, 41.61% graduate students; 40.51% male, 59.49% female). The proportion of students with depressive symptoms was 9.1% in Period 1, 36.1% in Period 2, and 34.67% in Period 3. Depressive symptoms increased notably with the introduction of the quarantine in Periods 2 and 3. Lower satisfaction with the food supplied and a longer duration of physical exercise per day were found to be positively associated with changes in depression severity in Periods 2 and 3. Quarantine-related psychological distress was more evident in students who were in a romantic relationship than in students who were single. Conclusion: Depressive symptoms in university students rapidly increased after 2 weeks of quarantine and no perceptible reversal was observed over time. Concerning students in a relationship, ways to take physical exercise and to relax should be provided and the food supplied should be improved when young people are quarantined.

Face-specific negative bias of aesthetic perception in depression: Behavioral and EEG evidence.

Introduction: Symptoms of depression are associated with the dysfunction of neural systems such as the emotion, reward system, and the default mode network. These systems were suggested by the model of neuroaesthetics as key contributions to aesthetic experience, leading to the prediction of atypical aesthetic orientation in depression. Here we investigated the aesthetic characteristics of depression and the corresponding neural underpinnings. Methods: Fifty-two (25 depression patients, 27 healthy controls) participants were asked to make aesthetic judgments on faces and landscapes in an electroencephalographic (EEG) experiment. Results: Our results indicate that relative to the controls, the depression tended to give ugly judgments and refrained from giving beautiful judgments, which was observed only for faces but not for landscapes. We also found that the face-induced component N170 was more negative in the depression group than the control group for ugly and neutral faces. Moreover, the aesthetic evaluation of ugly faces was associated with decreased N200 negativity in the depression group than in the control group, while the evaluation of beautiful faces was associated with decreased brain synchronization at the theta band. Discussion: These results suggested a face-specific negative aesthetic bias in depression which can help to design and develop aesthetics-oriented schemes in assisting the clinical diagnosis and therapy of depression.

A natural marmoset model of genetic generalized epilepsy.

Epilepsy has been extensively studied as a common neurological disease. Efforts have been made on rodent and other animal models to reveal the pathogenic mechanisms of epilepsy and develop new drugs for treatment. However, the features of current epilepsy models cannot fully mimic different types of epilepsy in humans, hence non-human primate models of epilepsy are required. The common marmoset (Callithrix jacchus) is a New World monkey that is widely used to study brain function. Here, we present a natural marmoset model of generalized epilepsy. In this unique marmoset family, generalized epilepsy was successfully induced by handling operations in some individuals. We mapped the marmoset family with handling-sensitive epilepsy and found that the epileptic phenotype can be inherited. These marmosets were more sensitive to the epilepsy inducers pentylenetetrazol. Using electrocorticogram (ECoG) recordings, we detected epileptiform discharge in marmosets with a history of seizures. In summary, we report a family of marmosets with generalized seizures induced by handling operations. This epileptic marmoset family provides insights to better understand the mechanism of generalized epilepsy and helps to develop new therapeutic methods.

Nicotinamide, a vitamin B3 ameliorates depressive behaviors independent of SIRT1 activity in mice.

Sirtuin 1 (SIRT1), is a nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylase and a candidate gene for depression. Nicotinamide (NAM), a form of vitamin B3, is reported as a potential inhibitor of SIRT1. Our previous study found that the 24-h-restraint stress could induce long-term depressive-like phenotypes in mice. These mice displayed increased SIRT1 activity. Here, we studied whether NAM was capable of attenuating depressive behaviors through inhibiting SIRT1 activity. Surprisingly, the application of NAM significantly reversed the depressive behaviors but increased SIRT1 activity further. In contrast, the level of adenosine triphosphate (ATP) was reduced in the restraint model for depression, and recovered by the administration of NAM. Furthermore, the Sirt1flox/flox; Nestin-Cre mice exhibited antidepressant behaviors and increased ATP levels. These data suggest that ATP plays an important role in depression pathogenesis, and NAM could be a potential treatment method for depression by regulating ATP independent of SIRT1 activity.

Dysregulation of neuron differentiation in an autistic savant with exceptional memory.

Autism spectrum disorder (ASD) is a heterogeneous group of complex neurodevelopmental disorders without a unique or definite underlying pathogenesis. Although savant syndrome is common in ASD, few models are available for studying the molecular and cellular mechanisms of this syndrome. In this study, we generated urinary induced pluripotent stem cells (UiPSCs) from a 13-year-old male autistic savant with exceptional memory. The UiPSC-derived neurons of the autistic savant exhibited upregulated expression levels of ASD genes/learning difficulty-related genes, namely PAX6, TBR1 and FOXP2, accompanied by hypertrophic neural somas, enlarged spines, reduced spine density, and an increased frequency of spontaneous excitatory postsynaptic currents. Although this study involved only a single patient and a single control because of the rarity of such cases, it provides the first autistic savant UiPSC model that elucidates the potential cellular mechanisms underlying the condition.

Low-frequency stimulation of the primary focus retards positive transfer of secondary focus.

Positive transfer of secondary focus (PTS) refers to new epileptogenesis outside the primary focus and is minimally controlled by existing treatments. Low-frequency stimulation (LFS) has benefits on the onset of epilepsy and epileptogenesis. However, it's unclear whether LFS can retard the PTS in epilepsy. Here we found that PTS at both contralateral amygdala and ipsilateral hippocampus were promoted after the primary focus was fully kindled in rat kindling model. The promotion of PTS at the mirror focus started when the primary kindling acquisition reached focal seizures. LFS retarded the promotion of PTS when it was applied at the primary focus during its kindling acquisition, while it only slightly retarded the promotion of PTS when applied after generalized seizures. Meanwhile, we found the expression of potassium chloride cotransporter 2 (KCC2) decreased during PTS, and LFS reversed this. Further, the decreased expression of KCC2 was verified in patients with PTS. These findings suggest that LFS may be a potential therapeutic approach for PTS in epilepsy.

Klotho protects against LPS-induced inflammation injury by inhibiting Wnt and NF-κB pathways in HK-2 cells.

AIM: This study aimed to investigate the effect and mechanism of Klotho in lipopolysaccharide (LPS)-induced inflammation injury in HK-2 cells. METHODS: We established LPS-induced inflammation injury model in HK-2 cells. The LPS-induced HK-2 cells were transfected with pc-Klotho, pcDNA3.1, siKlotho or siNC. Cell viability, apoptosis and reactive oxygen species (ROS) level were detected by MTT assay, Annexin V-FITC/PI Apoptosis Detection kit and 2,7-dichlorofluorescein diacetate, respectively. The levels of inflammatory factors and the expressions of proteins related to Wnt and nuclear factor-κB (NF-κB) signaling pathway were detected by RT-qPCR and western blotting, respectively. RESULTS: Compared with cells transfected with pcDNA 3.1, cell viability was remarkably increased and cell apoptosis rate was decreased in LPS-induced cells with pc-Klotho (p < 0.05). Conversely, LPS-induced cells with siKlotho showed lower cell viability and higher cell apoptosis rate than cells with siNC (p < 0.05). The levels of ROS, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) was significantly reduced in LPS-induced cells with pc-Klotho compared with cells with pcDNA3.1 (p < 0.05). Consistently, LPS-induced cells with siKlotho showed increased levels of ROS, TNF-α and IL-6 compared with cells with siNC (p < 0.05). Wnt signaling pathway related protein Wnt3a and NF-κB signaling pathway related to proteins p-IκBα were significantly down-regulated in LPS-induced cells with pc-Klotho compared with cells with pcDNA3.1, while up-regulated in LPS-induced cells with pc-Klotho compared with cells with pcDNA3.1 (p < 0.05). CONCLUSIONS: Klotho may play an inhibiting role in LPS-induced inflammation injury by inhibiting NF-κB and Wnt signaling pathways in HK-2 cells.

Low-frequency stimulation in anterior nucleus of thalamus alleviates kainate-induced chronic epilepsy and modulates the hippocampal EEG rhythm.

High-frequency stimulation (HFS) of the anterior nucleus of thalamus (ANT) is a new and alternative option for the treatment of intractable epilepsy. However, the responder rate is relatively low. The present study was designed to determine the effect of low-frequency stimulation (LFS) in ANT on chronic spontaneous recurrent seizures and related pathological pattern in intra-hippocampal kainate mouse model. We found that LFS (1 Hz, 100 µs, 300 µA), but not HFS (100 Hz, 100 µs, 30 µA), in bilateral ANT significantly decreased the frequency of spontaneous recurrent seizures, either non-convulsive focal seizures or tonic-clonic generalized seizures. The anti-epileptic effect persisted for one week after LFS cessation, which manifested as a long-term inhibition of the frequency of seizures with short (20-60 s) and intermediate duration (60-120 s). Meanwhile, LFS decreased the frequency of high-frequency oscillations (HFOs) and interictal spikes, two indicators of seizure severity, whereas HFS increased the HFO frequency. Furthermore, LFS decreased the power of the delta band and increased the power of the gamma band of hippocampal background EEG. In addition, LFS, but not HFS, improved the performance of chronic epileptic mice in objection-location task, novel objection recognition and freezing test. These results provide the first evidence that LFS in ANT alleviates kainate-induced chronic epilepsy and cognitive impairment, which may be related to the modulation of the hippocampal EEG rhythm. This may be of great therapeutic significance for clinical treatment of epilepsy with deep brain stimulation.

Low-frequency stimulation of the external globus palladium produces anti-epileptogenic and anti-ictogenic actions in rats.

AIM: To investigate the anti-epileptic effects of deep brain stimulation targeting the external globus palladium (GPe) in rats. METHODS: For inducing amygdala kindling and deep brain stimulation, bipolar stainless-steel electrodes were implanted in SD rats into right basolateral amygdala and right GPe, respectively. The effects of deep brain stimulation were evaluated in the amygdala kindling model, maximal electroshock model (MES) and pentylenetetrazole (PTZ) model. Moreover, the background EEGs in the amygdala and GPe were recorded. RESULTS: Low-frequency stimulation (0.1 ms, 1 Hz, 15 min) at the GPe slowed the progression of seizure stages and shortened the after-discharge duration (ADD) during kindling acquisition. Furthermore, low-frequency stimulation significantly decreased the incidence of generalized seizures, suppressed the average stage, and shortened the cumulative ADD and generalized seizure duration in fully kindled rats. In addition, low-frequency stimulation significantly suppressed the average stage of MES-induced seizures and increased the latency to generalized seizures in the PTZ model. High-frequency stimulation (0.1 ms, 130 Hz, 5 min) at the GPe had no anti-epileptic effect and even aggravated epileptogenesis induced by amygdala kindling. EEG analysis showed that low-frequency stimulation at the GPe reversed the increase in delta power, whereas high-frequency stimulation at the GPe had no such effect. CONCLUSION: Low-frequency stimulation, but not high-frequency stimulation, at the GPe exerts therapeutic effect on temporal lobe epilepsy and tonic-colonic generalized seizures, which may be due to interference with delta rhythms. The results suggest that modulation of GPe activity using low-frequency stimulation or drugs may be a promising epilepsy treatment.

Serotonin 1A receptor inhibits the status epilepticus induced by lithium-pilocarpine in rats.

Status epilepticus (SE) is a life-threatening neurological emergency associated with a high mortality rate. The serotonin 1A (5-HT1A) receptor is a possible target for the treatment of SE, but its role in animal models and the precise area of brain involved remain controversial. The hippocampus is a candidate site due to its key role in the development of SE and the existence of a high density of 5-HT1A receptors. Therefore, we investigated the effects of subcutaneous and intrahippocampal activation of 5-HT1A receptors in lithium-pilocarpine-induced SE, and tested whether the hippocampus is a true effector site. We developed SE in male Sprague-Dawley rats by giving lithium chloride (LiCl; 3 meq/kg, i.p.) 22-24 h prior to pilocarpine (25 mg/kg, i.p.), and found that 8-OH-DPAT, a 5-HT1A receptor agonist administered subcutaneously (s.c.) at 0.5 or 1.0 mg/kg 1 h before pilocarpine injection increased the latency to the first epileptiform spikes, the electrographic SE, and the behavioral generalized seizures (GS), while reducing the total EEG seizure time (P <0.01). The duration of GS was shortened only by 1.0 mg/kg 8-OH-DPAT s.c. (P <0.05). All these effects were inhibited by combined administration of WAY-100635 (1.0 mg/kg, s.c.) (P <0.05), an antagonist of the 5-HT1A receptor, but WAY-100635 alone and low doses of 8-OHDPAT (0.01 and 0.1 mg/kg) did not alter seizure activity. Furthermore, intrahippocampal 8-OH-DPAT only shortened the GS duration (P <0.05). These findings imply that the 5-HT1A receptor is a promising therapeutic target against the generation and propagation of SE, and hippocampal receptors are involved in reducing the seizure severity.