FGF2 gene's antisense protein, NUDT6, plays a depressogenic role by promoting inflammation and suppressing neurogenesis without altering FGF2 signalling.

Fibroblast growth factor-2 (FGF2) is involved in the regulation of affective behaviour and shows antidepressant effects through the Akt and extracellular signal regulated kinase (ERK) 1/2 pathways. Nudix hydrolase 6 (NUDT6) protein is encoded from FGF2 gene's antisense strand and its role in the regulation of affective behaviour is unknown. Here, we overexpressed NUDT6 in the hippocampus and investigated its behavioural effects and the underlying molecular mechanisms affecting the behaviour. We showed that increasing hippocampal NUDT6 results in depression-like behaviour in rats without changing FGF2 levels or activating its downstream effectors, Akt and ERK1/2. Instead, NUDT6 acted by inducing inflammatory signalling, specifically by increasing S100 calcium binding protein A9 (S100A9) levels, activating nuclear factor-kappa B-p65 (NF-κB-p65), and elevating microglia numbers along with a reduction in neurogenesis. Our results suggest that NUDT6 could play a role in major depression by inducing a proinflammatory state. This is the first report of an antisense protein acting through a different mechanism of action than regulation of its sense protein. The opposite effects of NUDT6 and FGF2 on depression-like behaviour may serve as a mechanism to fine-tune affective behaviour. Our findings open up new venues for studying the differential regulation and functional interactions of sense and antisense proteins in neural function and behaviour, as well as in neuropsychiatric disorders. KEY POINTS: Hippocampal overexpression of nudix hydrolase 6 (NUDT6), the antisense protein of fibroblast growth factor-2 (FGF2), increases depression-like behaviour in rats. Hippocampal NUDT6 overexpression triggers a neuroinflammatory cascade by increasing S100 calcium binding proteinA9 (S100A9) expression and nuclear NF-κB-p65 translocation in neurons, in addition to microglial recruitment and activation. Hippocampal NUDT6 overexpression suppresses neurogenesis. NUDT6 exerts its actions without altering the levels or downstream signalling pathways of FGF2.

Repeated Collection of Vaginal Smear Causes Stress in Mice.

Introduction: Women are more likely to be misdiagnosed in many neuropsychiatric disorders than men. One of the possible underlying reasons for this disparity may be more frequent use of male mice than female mice in neuroscience studies. With the increasing realization of the shortcomings of this approach in understanding the neurobiological basis of these disorders, many funding agencies mandate the inclusion of both male and female subjects in study design. As the behaviors vary with the stage of the estrous cycle, the collection of vaginal smears to identify the estrous stage becomes a widely used procedure. Here we tested whether vaginal smear collection causes similar effects to that of stress by evaluating an increase in depression-like behavior and impairment in memory. Method: Vaginal smear was collected from Swiss albino mice twice a day for 10 days. In order to test depression-like behavior tail suspension, sucrose preference and splash tests were conducted. Novel object recognition and novel object location tests were performed 1 hour and 24 hours after training to evaluate short-and long-term memory respectively. Results: The female mice whose vaginal smears were collected demonstrated increased behavioral despair and anhedonia. Vaginal smear group showed deficits in both short-term and long-term memory when compared to the control group. Conclusion: Our results indicate that the collection of vaginal smear not only increased depression-like behaviors in mice, but also impaired short-term and long-term memory, indicating that the procedure of vaginal smear collection was stressful. We recommend to consider other ways of estrous cycle staging when studying behavior.

The relationship between premature ejaculation and the timing of pre-adult circumcision.

We aimed to investigate the relationship between premature ejaculation and the age when men had been circumcised before adulthood. A total of 2,768 sexually active male patients aged between 18 and 65 years were included in this study. A multicentre study was conducted prospectively with the participation of 20 centres. A survey consisting of 12 questions prepared by the researchers, as well as the validated Turkish versions of the five-item Premature Ejaculation Diagnostic Tool, was administered to all participants. The study included 1,603 participants who met the inclusion criteria. There was no significant difference in the Premature Ejaculation Diagnostic Tool and self-reported ejaculation time between the participants who had been circumcised at different ages during childhood. Remembering circumcision experience with fear or anxiety did not increase the risk of sexual dysfunction compared to the participants who described their experience with happiness or with no particular emotion. There was no significant difference in Premature Ejaculation Diagnostic Tool scores or the self-reported ejaculation time of the participants circumcised at different ages. The age of childhood circumcision, having a fearful or anxious circumcision experience, does not affect the risk of premature ejaculation in adult life.

Relationship between panic disorder and plasma neuropeptide-S level

Abstract Background: Panic disorder has long been associated with the changes in various neurotransmitters, such as Neuropeptide-S (NPS). Objective: In this study we aimed to determine whether there is a relationship between blood NPS levels and panic disorder. Methods: Twenty nine patients with panic disorder and thirty two healthy control subjects who were age and gender matched were enrolled to the study. Blood samples were taken from participants and plasma NPS levels were quantified by using an ELISA kit. Results: In the study group, median NPS blood level was 16.7 pg/mL and in the control group it was 32.5 pg/mL. There was a statistically significant difference (p = 0.021). Using receiver operating characteristics (ROC) curve, sensitivity and specificity of NPS blood level, for diagnosing panic disorder was calculated, and it was found 79.3% and 56.25% respectively (AUC:0.672, 95% CI: 0.540-0.787). Discussion: Malfunction at the NPS modulatory system in the cortical areas (which is causing excitations in brain areas, such as amygdala and hypothalamus) does not only increase anxiety symptoms and risk of panic disorder but also causes panic disorder patients to have lower plasma NPS levels than the control group. Therefore it can be argued that such malfunction can be treated with a systemic treatment. Baykan H et al. / Arch Clin Psychiatry. 2018;45(4):79-81

Microvascular functions in patients with fibromyalgia syndrome: effects of physical exercise.

OBJECTIVES: This study aims to evaluate the current state of microvascular function and to investigate the effect of supervised aerobic exercise on microvascular control mechanisms and health outcomes in women with fibromyalgia syndrome (FMS). PATIENTS AND METHODS: Forty female patients (mean age 51±11 years) with a diagnosis of FMS according to the American College of Rheumatology criteria and 20 healthy female controls (mean age 52±9 years) were included in the study. Microvascular blood flow was measured using a laser Doppler flowmeter (LDF) at the volar skin site of the forearm. Pain severity and FMS were assessed using the visual analog scale (VAS) and Fibromyalgia Impact Questionnaire (FIQ), respectively, both at the beginnig and at the end of the study. Fibromyalgia was evaluated and a spectral analysis of LDF signals was carried out to assess the relative contribution of each control mechanisms. The local thermal hyperemia was used to test the microvascular functions. Moderate-intensity aerobic activity (energy expenditure 3.0 to 6.0 metabolic equivalent) was performed by treadmill walking for 30 min for five days each week for a month. RESULTS: The patients with FMS had lower VAS and FIQ scores at the end of the exercise period. There was a positive correlation between improved myogenic and neurogenic mechanisms and reduced FIQ scores. Cardiac signals were positively correlated with the FIQ scores at the end of the exercise period. Endothelial function was under the influence of pain, and baseline nitric oxide activity was found to be positively correlated with VAS. CONCLUSION: Our study results suggest that microvascular functions are impaired in FMS patients and moderate exercise training is effective to improve the FIQ/VAS scores and enhance vascular functions.

Automated discrimination of psychotropic drugs in mice via computer vision-based analysis.

We developed an inexpensive computer vision-based method utilizing an algorithm which differentiates drug-induced behavioral alterations. The mice were observed in an open-field arena and their activity was recorded for 100 min. For each animal the first 50 min of observation were regarded as the drug-free period. Each animal was exposed to only one drug and they were injected (i.p.) with either amphetamine or cocaine as the stimulant drugs or morphine or diazepam as the inhibitory agents. The software divided the arena into virtual grids and calculated the number of visits (sojourn counts) to the grids and instantaneous speeds within these grids by analyzing video data. These spatial distributions of sojourn counts and instantaneous speeds were used to construct feature vectors which were fed to the classifier algorithms for the final step of matching the animals and the drugs. The software decided which of the animals were drug-treated at a rate of 96%. The algorithm achieved 92% accuracy in sorting the data according to the increased or decreased activity and then determined which drug was delivered. The method differentiated the type of psychostimulant or inhibitory drugs with a success ratio of 70% and 80%, respectively. This method provides a new way to automatically evaluate and classify drug-induced behaviors in mice.

Effects of partial bladder outlet obstruction on contraction and relaxation response of rabbit corpus cavernosum.

It has been well established that erectile dysfunction (ED) is a common incident in patients with benign prostate hyperplasia. Animal models have been described to investigate the relationship between bladder obstruction and ED. In this study, we aimed to investigate whether partial bladder outlet obstruction (PBOO) induces changes in the contraction and relaxation response of corpus cavernosum smooth muscle (CCSM) of the penis in the rabbit model. Partial bladder obstruction was performed in rabbits as previously described. After 2 and 4 weeks of follow-up, control, sham-operated (2- and 4-week duration) and partial bladder outlet obstructed (obstruction of 2- and 4-week duration) rabbits were sacrificed and their bladder masses determined. Then CCSM tissue was obtained. Contraction responses induced by 124 mM KCl, phenylephrine (10(-6) to 10(-4)M) and relaxation responses induced by doxazosin (10(-7) to 10(-5)M) in CCSM of rabbits were determined. The obtained contraction and relaxation responses of all groups were compared. Bladder weight was significantly higher in PBOO groups than in control and sham-operated rabbits. Contraction responses induced by KCl and phenylephrine were statistically enhanced in the 4-week PBOO groups than controls. However, there was no statistically significant difference in any KCl, phenylephrine and doxazosin responses between 2- and 4-week sham-operated and PBOO groups. The rabbit model of PBOO described for the studies which examine bladder responses is useful for creating bladder outlet obstruction. However, this model is not suitable for the investigation of outlet obstruction-related ED.