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.

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.