Affective Behavior Shows Sex Differences in Mid-adulthood Rats Following Postnatal Immune Stimulation.

Mid-adulthood represents the critical window period usually associated with the development of age-related diseases. Despite several attempts to delineate the pathological mechanisms underlying postnatal immune challenge and altered brain functions, the role of sex-dependent changes in affective behaviors of middle-aged animals requires more attention. In this study, we sought to investigate behavioral and molecular response patterns at mid-adulthood linked to early-life immune activation. Using affective behavioral test batteries, we showed that lipopolysaccharide (LPS)-induced postnatal immune challenge caused anxiety-like behaviors in both male and female Wistar rats at mid-adulthood, whereas only female rats exhibited depression-like behaviors. Our data further demonstrated a significant increase in microglial complexity and increased levels of tumor necrosis factor (TNFα), nitric oxide (NOx), and lipid peroxidation in the prefrontal cortex of female rats compared to their male counterparts and phosphate-buffered saline (PBS) littermate controls. With these results, we established significant interaction between sex differences and LPS-induced alterations in behavior and associated oxidative and immunohistochemical changes. These findings may provide an insight to better understand the neuroimmunological mechanisms of sex-dependent brain pathological manifestations occurring at mid-adulthood.

A systematic review of contemporary management of oligometastatic prostate cancer: fighting a challenge or tilting at windmills?

PURPOSE: Amongst the unanswered questions regarding prostate cancer (PCa), the optimal management of oligometastatic disease remains one of the major concerns of the scientific community. The very existence of this category is still subject to controversy. Aim of this systematic review is to summarize current available data on the most appropriate management of oligometastatic PCa. EVIDENCE ACQUISITION: All relevant studies published in English up to November the 1st were identified through systematic searches in PubMed, EMBASE, Cochrane Library, CINAHL, Google Scholar and Ovid database. A search was performed including the combination of following words: (prostate cancer) and (metastatic) and [(oligo) or (PSMA) or (cytoreductive) or (stereotaxic radiotherapy) or (prostatectomy)]. 3335 articles were reviewed. After title screening and abstract reading, 118 papers were considered for full reading, leaving a total of 36 articles for the systematic review. EVIDENCE SYNTHESIS: There is still no consensus on the definition of oligometastatic disease, nor on the imaging modalities used for its detection. While retrospective studies suggest an added benefit with the treatment the primitive tumor by cytoreductive prostatectomy (55% survival rate vs 21%, p < 0.001), prospective studies do not validate the same outcome. Nonetheless, most studies have reported a reduction in local complications after cytoreductive prostatectomy (< 10%) compared to the best systemic treatment (25-30%). Concerning radiotherapy, an overall survival benefit for patients with a low metastatic burden was found in STAMPEDE (HR 0.68, 95% CI 0.52-0.90; p = 0.007) and suggested in subgroup analysis of the HORRAD trial. Regarding the impact of metastases-directed therapy (MDT), the STOMP and ORIOLE trials suggested that metastatic disease control might improve androgen deprivation therapy-free survival (in STOMP: 21 vs 13 months for MDT vs standard of care). Nonetheless, the impact of MDT on long-term oncologic results remains unclear. Finally, oligometastatic disease appears to be a biologically different entity compared to high-burden metastatic disease. New findings on exosomes appear to make them intriguing biomarkers in the early phases of oligometastatic PCa. CONCLUSION: Oligometastatic PCa is today a poorly understood disease. The implementation of new imaging techniques as whole-body MRI and PSMA PET/CT has increased exponentially the number of oligometastatic patients detected. Data of available trials suggest a benefit from cytoreductive prostatectomy to reduce local complication, though its impact on survival remains unknown. Radiotherapy may be beneficial for patients with low-burden metastatic PCa, while MDT may delay the need for androgen deprivation therapy. Results from ongoing trials data are eagerly awaited to draw reliable recommendations.

Pelvic salvage (SBRT) radiotherapy based on 68Ga-PSMA PET/CT: About a case.

Very few patients with a biochemical failure after radical prostatectomy respond to prostatic bed irradiation. In this setting, 68Ga-PSMA PET/CT seems to be a useful tool for the detection of lesions remaining occult to conventional imaging work-up, changing the treatment strategy in a significant percentage of patients. we report the case of a patient in whom the PSMA PET allowed orientation of the SBRT. To date the patient has no recurrence.

The sex differences of the behavior response to early Life immune stimulation: Microglia and astrocytes involvement.

It is well known that inflammatory challenge during the prenatal period results in permanent changes in glial cells and behavior in adulthood. However, it is unknown whether inflammatory challenge during the infantile period may have permanent sexually-dimorphic effects on microglia and astrocytes in vivo, which in turn may be associated with sex differences in adult behavior. In this study, we have evaluated whether postnatal injection of lipopolysaccharide (LPS; 250µg/kg, i.p. on postnatal day 14) induces depressive and less anxiety-like behaviors, glial cell activation, pro-inflammatory cytokine (TNF-alpha) secretion and sexually dimorphic responses in adulthood. Postnatal day 14 (P14) male and female Wistar rats received an intraperitoneal (ip) injection of LPS or PBS. Three months later, animals were tested in the Open Field (OF), the Elevated Plus Maze (EPM) and the Forced Swimming Test (FST) to assess the level of anxiety and depression-like behavior. Hippocampal proinflammatory cytokine TNF-alpha concentration and the number of astrocytes and microglia were estimated in the dentate gyrus, CA1, and CA3 in two regions of the hippocampus (ventral and dorsal). Our results showed that the administration of LPS resulted in less anxiety and depression-like behavior in males but not in females. However, the LPS-administration increased the number of microglia in the dorsal and ventral hippocampus areas in females more than male, while no significant differences in TNFα level had been detected between the LPS-rats treated and their controls. Interestingly, LPS resulted in an increase in the number of astrocytes in both areas of the hippocampus in a female. While in a male, our results showed a decrease in astrocytes number in the dorsal hippocampus, but no significant differences observed in ventral hippocampus. These findings indicate that an immune challenge in infantile rats induces a ventral and dorsal hippocampus damage in female more than in male, without affecting significantly the affective behavior changes in the female. The results also showed that small changes in the male hippocampus can affect the behavior and induce a depression-like behavior.

Using the radioligand-receptor binding assay for paralytic shellfish toxins: A case study on shellfish from Morocco.

Paralytic shellfish poisoning (PSP) events occur regularly along the Mediterranean and Atlantic coast of Morocco, and have been responsible for several severe cases of human intoxication. Along the southern Atlantic coast of Morocco, aquaculture and intensive artisanal fishing practices have recently been particularly heavily impacted, and toxic species have been observed in increasing intensity and frequency. In the 1990's a regulatory monitoring program was established for the coastal waters off Morocco by the National Institute of Fisheries Research (INRH), to reduce the risk of intoxication with biotoxins. The regulatory monitoring is conducted weekly and includes toxic phytoplankton enumeration and identification, as well as saxitoxin (STX) analysis in seafood using the mouse bioassay (MBA). Animal testing remains the most widely used screening method for PSP toxin detection, yet its use is being reconsidered for animal-related ethical issues, as well as for practical considerations. To be able to better evaluate alternatives to animal testing, the performance of a nuclear-based radioligand-receptor binding assay (RBA) for paralytic shellfish toxins was assessed and compared with the MBA using four commercially important shellfish matrices, including cockles Cerastoderma edule, razor shells Solen marginatus, oysters Crassostrea gigas, and mussels Perna perna. Over 50 samples were collected and analysed as part of the regulatory monitoring framework including a suite of monthly samples from 2017 and all samples identified as toxic by MBA since 2011. Testing of reference material and evaluation of assay-critical parameters (e.g. slope of calibration curve, internal quality control QC and IC50) confirmed the robustness of the RBA methodology. With this RBA method, STX-like activity detected in shellfish samples ranged from 33 to 8500 µg STX equivalents per kg. RBA data were significantly correlated (P < 0.0001, Pearson r = 0.96) with the MBA-derived dataset. Importantly, the RBA method allowed for the detection and quantification of PSP toxins at levels not detectable by using the mouse bioassay. The limits of quantification of the RBA was calculated and found to be 10-fold lower than that of the MBA, respectively 35.24 ±â€¯5.99 and 325 µg STX equivalents per kg of tissue. In addition, the RBA was easier to use and produced reliable results more rapidly than the MBA and without use of live animals. Considering the increasing risks associated with harmful algal blooms, globally and in Morocco, together with the increased development of aquaculture production and seafood consumption and the difficulties of live animal testing, these findings indicate that the RBA method is a reliable and effective alternative to the MBA method.

Thymelaea lythroides extract attenuates microglial activation and depressive-like behavior in LPS-induced inflammation in adult male rats.

Thymelaea lythroides extract is widely used as a traditional folk medicine in Morocco, especially for the treatment of diabetes, rheumatism and Inflammatory disease. The aim of the study is to evaluate the possible effect of methanolic extract of Thymelaea lythroides in repressing the inflammatory responses and long-lasting depression-like behavior associated with neuroinflammation in adult rats after neonatal LPS exposure. Male rat pups were treated systemically with either LPS (250??g/kg) or vehicle (phosphate buffer saline) on postnatal day 14. Six hours later, the LPS groups were assigned to intraperitoneal (ip) injection of Minocycline (50?mg/kg) or Thymelaea lythroides (200?mg/kg). Thereafter, in adulthood (postnatal days 90-97), the spontaneous locomotor activity and depression-like behavior were assessed successively in open field and forced swim tests. The levels of proinflammatory cytokines, oxidative damage, and activation of microglia were determined in the hippocampus (HP) of male rats on (PND90-97). Our results showed that open field hypoactivity and increased immobility period in LPS-induced adult rats were normalized on treatment with Thymelaea lythroides and minocycline. Both treatments attenuate the overactivated microglial cells in the CA1 and CA3 of hippocampus (HP) and significantly reduced the oxidative-nitrosative stress markers and cytokine (TNF ?) production in the HP. Thymelaea lythroides seems to have similar neuroprotective effects to Minocycline, and such protection may be due to: reduction of oxidative stress, upregulation of inflammatory mediators production, antidepressant behavior which all are associated with neuroinflammation.

Postnatal melatonin treatment protects against affective disorders induced by early-life immune stimulation by reducing the microglia cell activation and oxidative stress.

BACKGROUND: Systemic inflammation induced by neonatal infection may result as long-term hyper-activation of microglial cells followed by an overproduction of pro-inflammatory cytokines, such as tumor necrosis factor-alpha, nitric oxide and lipid peroxidation. Those inflammation mediators can trigger behavioral disruption and/or cognitive disorders. OBJECTIVE: The present work aims to evaluate the effect of melatonin (a cytokine release modulator and antioxidant agent) in the reduction of the prefrontal microglia activation and depressive-like behaviors induced by lipopolysaccharide (LPS) injection in adult rats. RESULTS: The effect of melatonin (5 mg/kg) was compared to minocycline (50 mg/kg), a well-known anti-inflammatory drug with potent inhibitory effect on microglial activation. Our results showed that LPS injection induced a significant increase in prefrontal cortex tumor necrosis factor-alpha and nitric oxide levels. Furthermore, lipid peroxidation and microglial activation were highly increased in the prefrontal cortex compared to control. The melatonin treatment induced a significant decrease on nitric oxide and lipid peroxidation levels in the prefrontal cortex and significant decrease on tumor necrosis factor-alpha and microglia activation. Melatonin can also induce a significant reduction in the anxiety and depression-like effect induced by PND9 LPS administration. CONCLUSION: Our results demonstrated that melatonin possesses potent protective effect against the depression and anxiety induced by LPS. The underlying effect of melatonin is probably due to the reduction of nitric oxide toxic effect and lipid peroxidation in addition to its anti-inflammatory effect.

Preventive effects of flaxseed and sesame oil on bone loss in ovariectomized rats.

A study was designed to examine the effects of dietary flaxseed oil (FO) and sesame oil (SO) which are rich successively in n-3 and (n-9 and n-6) on biochemical parameters and histological status of bone. Sixty-four 90-day-old female wistar rats were randomly assigned to 6 groups: sham-operated rat (sham)+ control diets, ovariectomized rat (OVX) + control diets, OVX + 7% FO, OVX + 7% SO, OVX + 10% FO, OVX + 10% SO. After 4 weeks of treatments, rats were euthanized; blood and tissues were collected for analyses. Markers of bone formation which is alkaline phosphatase activity and markers of bone resorption which is tartrate resistant acid phosphatase activity were measured. Present results showed that OVX increased significantly ALP and TRAP activity and the examination of bone tissue showed disruptive and lytic bone trabeculae. Animals fed 10% FO and 10% SO of fat reduced these parameters and improved bone microarchitecture. Whereas, there was no improvement in biochemical and histological states in OVX rats that received 7% of PUFAs successively provided from FO and SO diets. In conclusion, our results are encouraging because they suggest that PUFAs intake may help to prevent osteoporosis associated with estrogens deficiency. However, further studies are needed to determine the mechanism by which a diet rich in n-3 or lignans modulate bone tissue.

Effects of photoperiod regimen on emotional behaviour in two tests for anxiolytic activity in Wistar rat.

Seasonal changes are often gone with mood and behaviour changes which are probably linked to change in day length or photoperiod. The experiments developed in this work are based on the hypothesis that changes in photoperiod affect emotionality in rats. To check this hypothesis, female rats were exposed to four different photoperiods (LP: 16L/8D; MP: 12L/12D; SP: 8L/16D; SP-F: 8L/16D with a light pulse in midpoint of the dark phase). Eight or 14 weeks later, rats were subjected to two behavioural tests to quantify anxiety level. Independently of duration, rats exposed to SP exhibited higher levels of anxious-like behaviour than rats raised in LP and SP-F, in an open field test (OFT) and in elevated plus maze (EPM). Significant differences in EPM are obtained only after 14 weeks of treatment. Moreover rats treated more long time showed greater suprarenal gland mass. Compared to all other groups, females exposed to SP had greater suprarenal gland. Our results indicate that changes in day length are associated with different levels of anxious-like behaviours consistent with the conjecture that short days may have an anxiogenic effect in female rats.

Effects of amphetamine and phenylethylamine on catecholamine release in the glomerular layer of the rat olfactory bulb.

In the present work, we have shown electrochemically that in the rat olfactory bulb (OB), extracellular dopamine (DA) was highest in the glomerular layer (GL), whereas extracellular noradrenaline (NA) appeared to be more uniformly distributed across layers. The GL catecholamine (CA) responses to amphetamine (AMPH) and phenylethylamine (PEA) were also characterized electrochemically using an in vivo model. Results of this investigation show that at a lower dose (1 mg/kg), PEA had no effect on CA release. In contrast, at a higher dose (10 mg/kg), it produced similar increases in either extracellular DA (17.5 +/- 7%) or extracellular NA (14 +/- 3%), and DA exhibited dose-independent increases to AMPH (93 +/- 8%: 1 mg/kg vs. 97 +/- 6%: 10 mg/kg) whereas NA exhibited dose-dependent increases to AMPH (24.5 +/- 6%: 1 mg/kg vs. 39 +/- 7%: 10 mg/kg). These data indicate that (i) PEA may increase CA release but less efficiently than AMPH. (ii) AMPH is more efficient on the DAergic than on the NAergic system since AMPH-induced DA release exceeded 2-4 times the AMPH-induced NA release.

Na+,K(+)-ATPase in the rat olfactory bulb: evidence for a higher enzymatic activity in the glomerular layer.

Protein content and ATPase activities have been determined in the superficial and deep layers of the rat olfactory bulb. Protein levels, Mg2(+)-ATPase and Na+,K(+)-ATPase activities were significantly higher in the whole homogenate for the superficial layers. These differences were amplified when activity was expressed on a wet weight basis in a crude microsomal preparation isolated by differential centrifugation. Specific activities, however, showed similar values in the microsomal fractions from superficial and deep layers. The results are discussed in terms of differences in the density of neuronal processes and efficiency of K+ reuptake mechanisms.