Neuroinflammation characterized by activation of glial cells is observed in various neurodegenerative diseases including Alzheimer's disease (AD). Although the reduction of ether-type glycerophospholipids, plasmalogens (Pls), in the brain is reported in AD patients, the mechanism of the reduction and its impact on neuroinflammation remained elusive. In the present study, we found for the first time that various inflammatory stimuli reduced Pls levels in murine glial cells via NF-κB activation, which then downregulated a Pls-synthesizing enzyme, glycerone phosphate O-acyltransferase (Gnpat) through increased c-Myc recruitment onto the promoter. We also found that systemic injection of lipopolysaccharide, aging, and chronic restraint stress reduced brain Pls contents that were associated with glial NF-κB activation, an increase in c-Myc expression, and downregulation of in the mouse cortex and hippocampus. More interestingly, the reduction of Pls contents in the murine cortex itself could increase the activated phenotype of microglial cells and the expression of proinflammatory cytokines, suggesting further acceleration of neuroinflammation by reduction of brain Pls. A similar mechanism of reduction was also found in human cell lines, triple-transgenic AD mouse brain, and postmortem human AD brain tissues. These findings suggest a novel mechanism of neuroinflammation that may explain prolonged progression of AD and help us to explore preventive and therapeutic strategies to treat neurodegenerative diseases. Ether-type glycerophospholipids, plasmalogens (Pls), are reduced in the brain of Alzheimer disease (AD) patients. We found that inflammatory stimuli reduced Pls contents by downregulation of the Pls-synthesizing enzyme glycerone phosphate O-acyltransferase (Gnpat) through NF-κB-mediated recruitment of c-Myc onto the promoter in both murine and human cell lines. Murine brains after systemic lipopolysaccharide, chronic stress, and aging, as well as triple-transgenic AD mice and postmortem human AD brain tissues all showed increased c-Myc and reduced expression. Interestingly, knockdown of itself activated NF-κB in glial cell lines and microglia in mouse cortex. Our findings provide a new insight into the mechanism of neuroinflammation and may help to develop a novel therapeutic approach for neurodegenerative diseases such as AD.

Microglial activation is a pathological feature of many neurodegenerative diseases and the role of cellular lipids in these diseases is mostly unknown. It was known that the special ether lipid plasmalogens (Pls) were reduced in the brain and blood samples of Alzheimer's disease (AD) patients. It has recently been reported that the oral ingestion of scallop-derived Pls (sPls) improved cognition among mild AD patients, which led us to investigate the role of sPls in the microglial activation. We used the lipopolysaccharides (LPS)-induced microglial activation model and found that sPls inhibit the LPS-mediated TLR4 endocytosis and the downstream caspases activation. By using the specific inhibitors, we also confirmed that the TLR4 endocytosis and the caspases activation strictly controlled the pro-inflammatory cytokine expression. In addition, the reduction of cellular Pls by sh-RNA-mediated knockdown of GNPAT (glyceronephosphate O-acyltransferase), a Pls synthesizing enzyme, enhanced the endocytosis of TLR4 and activation of caspase-3 which resulted in the enhanced pro-inflammatory cytokine expression. We also report for the first time that the TLR4 endocytosis was significantly higher in the cortex of aged mice and AD model mice brains, proposing a significant link between the age-related reduction of Pls and microglial activation. Interestingly, the sPls drinking in AD model mice significantly reduced the TLR4 endocytosis. Our cumulative data indicates that the cellular Pls attenuate the microglial activation by maintaining the endocytosis of TLR4, suggesting a possible mechanism of the cognition improvement effect of sPls among mild AD patients.

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Background and Aim: Estrus detection plays a crucial role in the success of animal reproduction. It was previously reported that body temperature changes during estrus. This study aimed to investigate the relationship between vaginal temperatures (VTs) measured by a data logger, ovarian activity, and hormonal cyclic changes in camels. Materials and Methods: Six mature, healthy, non-pregnant dromedary, and 10-12-year-old camels were included in the study. The ovarian activity was monitored with ultrasonography, and estrus behavior was evaluated using an active and virile male camel. Animals were inserted with a blank controlled internal drug release device attached with an intravaginal data logger. Every hour, the ambient temperature was recorded by another data logger. Blood samples were collected, and sera were used to measure estradiol and progesterone levels. Results: The whole follicular cycle lasted 25.41±1.36 days, and the maximum sizes of the dominant follicle in the first and second follicular waves were 1.63±0.27 cm and 1.94±0.42 cm, respectively. There was a significant positive correlation between the follicular diameter and estradiol-17β level (p<0.01, r=0.397). There was no correlation between the follicular diameter and progesterone level (p>0.05, r=0.038), which remained low during the whole period of the experiment. The mean daily VT was significantly correlated with the diameter of the dominant follicle (1.7-2.2 cm, p<0.01, r=0.52). Conclusion: Measurement of VT will improve the accuracy of estrus prediction. Further studies are recommended to validate VT in camel reproduction.

Neurotransmitters are mediators inside the nervous system responsible for transmitting neural-neural or neural-organs signals. Several neural studies have tried to unveil the role of such mediators whose action extended outside the nervous system such as immune, digestive, circulatory and reproductive systems. The present study aimed to investigate the role of the excitatory-glutamate and inhibitory-GABA transmitters in female rats reproduction including their effects on gonadotropins; luteinizing hormone (LH) and follicle stimulating hormone (FSH) and the sex steroids; estrogen (E2) and progesterone (P4) during the estrous cycle as well. Furthermore, the responsive changes on the ovarian tissue were also studied. Synthetic glutamate and GABA were injected intraperitoneally (ip) in those animals throughout four successive estrous cycles. Interestingly, the ip injections of glutamate increased the levels of LH, E2 and P4 but decreased those of FSH significantly. However, the ip injections of GABA significantly decreased the levels of LH in the 4th cycles and FSH throughout treatment period while it increased the levels of E2 and P4. All changes occurred in those reproductive hormones caused by glutamate has been recovered after cessation of glutamate and GABA injection except FSH, including; the 5th, 6th and 7th cycles. Regarding to histopathological examination, ovaries of treated rats showed deleterious changes. The glutamate-treated rats ovaries showed atrophy of the primary follicles with degenerative changes in those secondary and tertiary follicles with obvious degeneration in the granulosa cell layer with vacuolated cytoplasm. On the other hand, those received GABA showed degeneration of the oocytes with congestion of blood vessels supplying the corpora lutea (CL) associated with endothelial changes. The histopathological changes in CL have been improved after glutamate cessation while not changed after GABA cessation.

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To evaluate the impact of male-female cohabitation period on the fertility, hatchability, injuries response, and some hormonal estimates in Japanese quails. A total of 288 mature Japanese quails were equally divided into 3 groups (3 groups × 8 replicates × 12 birds), with 1 Male: 2 Females sex ratio. In the first group (control), male and female quails were reared continuously together, while the males in the second and third groups were reared together with females once or twice/wk times (24 h/ time), respectively throughout the experiment. The obtained results showed that final body weight ( FBW /g), fertility (%), and hatchability (%) in the second and third groups significantly ( P ≤ 0.01) increased compared with the control group. Laying quails in the second and third groups significantly ( P ≤ 0.01) produced more and heavier eggs, while the feed consumption and feed conversion ratio were significantly ( P ≤ 0.01) decreased compared with the control group. The injuries response for both sex in the second and third groups significantly ( P ≤ 0.01) decreased compared with the control group. The cloacal size (mm 2 ) for quails in the third group significantly ( P ≤ 0.01) increased than those of the first and second groups, while the testes (%) were not affected. The testosterone hormone concentration for male chickens in the second and third groups significantly ( P < 0.01) decreased, while the female progesterone hormone concentration (ng/mL) significantly ( P < 0.01) increased compared with the control group. The means of red blood cells ( RBC /106), white blood cells ( WBC /103), and hemoglobin (g/dL) for quails in the second and third groups significantly ( P < 0.01) increased, while heterophil/lymphocyte ( H/L ratio) significantly ( P < 0.01) decreased compared with the control group. Thus, it could be concluded that the reduction male-female cohabitation period of quails is recommended for improving the fertility and hatchability percentages as well as and some hormonal estimates.