Virgin coconut oil reverses behavioral phenotypes of letrozole-model of PCOS in Wistar rats via modulation of NRF2 upregulation.

Objectives: Polycystic ovarian syndrome (PCOS) is an endocrine disorder associated with insulin resistance, hyperandrogenism, and sub-infertility. Virgin coconut oil (VCO) has been reported to have health benefits, such as anti-inflammatory, anti-oxidant, and antiviral properties. This study investigated the effects of dietary VCO supplementation on memory and cognitive impairment in female rats with letrozole induced PCOS. Methods: Thirty female rats were randomly divided into five groups. All rats except controls were treated with letrozole for 21 days to induce PCOS and were subsequently treated for 14 days with 10% VCO, clomiphene (CLO), or VCO + CLO. Three neurobehavioral tests were conducted: elevated plus maze, Y maze, and novel object recognition tests. Results: Our results indicated statistically elevated serum concentrations of sex hormones in rats with PCOS, compared with the control and treated groups. In addition, all treated groups showed significant reversal of the low serum concentrations of catalase and down-regulated gene expression of Nrf2 in the hippocampus seen in the PCOS rats. In addition, gene expression of acetylcholine esterase was up-regulated in PCOS rats, and was statistically reverted in the VCO treated groups. Conclusion: Anxiety-like behavior and impaired short-term memory were observed in PCOS rats; however, VCO supplementation reversed these effects by modulating the gene expression of Nrf2 and AchE.

Microglia activation precedes the anti-opioid BDNF and NMDA receptor mechanisms underlying morphine analgesic tolerance.

Herein, we investigated the role of periaqueductal gray (PAG)-resident microglia in the development of morphine tolerance and its underlying mechanisms. We showed that clodronate and minocycline known as microglia inhibitors reversed morphine tolerance, providing proof that microglia activation has key role in the development of morphine tolerance. The microglia-mediated anti-opioid mechanism occurs via sequential BDNF release and NMDA expression. Experimental evidence is provided here as conditional bdnf knockout mice (bdnf⁻/⁻) failed to develop tolerance following Cre-recombinase adenovirus treatment. Increased BDNF expression followed microglia activation in acute minocycline treatment reversible manner. Following BDNF release, NR2A subunit of NMDA receptor was upregulated in anti-BDNF reversible manner showing the contribution of BDNF signaling in the control of NMDA receptor expression following chronic morphine treatment. Our data provide compelling evidence that microglia activation and BDNF release are key regulators in opioid tolerance mechanism via glutaminergic synapse plasticity.

Age-dependent dystonia in striatal Gγ7 deficient mice is reversed by the dopamine D2 receptor agonist pramipexole.

Gγ7 is enriched in striatum and forms a heterotrimeric complex with Gαolf /Gß, which is coupled to D1 receptor (D1R). Here, we attempted to characterize the pathophysiological, neurochemical, and pharmacological features of mice deficient of Gγ7 gene. Gγ7 knockout mice exhibited age-dependent deficiency in rotarod behavior and increased dystonia-like clasping reflex without loss of striatal neurons. The neurochemical basis for the motor manifestations using immunoblot analysis revealed increased levels of D1R, ChAT and NMDA receptor subunits (NR1 and NR2B) concurrent with decreased levels of D2R and Gαolf , possibly because of the secondary changes of decreased Gαolf /Gγ7-mediated D1R transmission. These behavioral and neurochemical changes are closely related to those observed in Huntington's disease (HD) human subjects and HD model mice. Taking advantage of the finding of D2R down-regulation in Gγ7 knockout mice and the dopamine-mediated synergistic relationship in the control of locomotion between D2R-striatopallidal and D1R-stritonigral neurons, we hypothesized that D2-agonist pramipexole would reverse behavioral dyskinesia caused by defective D1R/Gαolf signaling. Indeed, the rotarod deficiency and clasping reflex were reversed by pramipexole treatment under chronic administration. These findings suggest that Gγ7 knockout mice could be a new type of movement disorders, including HD and useful for the evaluation of therapeutic candidates.

Erythropoietic and anti-obesity effects of Garcinia cambogia (bitter kola) in Wistar rats.

The anti-obesity and erythropoietic effects of crude ethanolic extracts of Garcinia cambogia (bitter kola) seeds on Wistar rats (Rattus norvegicus) were investigated. The rats were divided into three dosage groups: A (0 mg/kg of body weight), B (200 mg/kg) and C (400 mg/kg). Weight changes, plasma lipoprotein levels and the lipid profile of the liver, gastrointestinal system and adipose tissue were monitored as indices for anti-obesity, while the RBC (red blood cell) count (assessed by using a haemocytometer) was monitored as a measure of erythropoiesis. The extract was administered by gavage for 5 weeks. The results for each test group was compared statistically with those for the control (P<0.05). Analysis of the results showed a significant increase in RBC counts in both test groups and a decrease in weights of experimental animals. There was a dose-dependent decrease in the plasma level of very-low-density lipoprotein and a dose-dependent increase in the level of chylomicrons. There was a slight, but significant, decrease in the level of high-density lipoprotein and a significant increase in the level of LDL (low-density lipoprotein). There was significant dose-dependent decrease in the TAG (triacylglycerol) pool of adipose tissue and the liver of the test groups, but a significant increase in the TAG pool of the gastrointestinal system. The increase in the TAG pool of the gastrointestinal system is possibly compensatory. The results therefore confirm that ethanolic extracts of G. cambogia seeds have both haematologically enhancing and anti-obesity effects. The decrease in the high-density-lipoprotein level and an increase in the LDL level may play an important role in cardiovascular disease.