Background: A high-fat diet (HFD) can induce obesity and metabolic disorders that are closely associated with cognitive impairments, and the progression of several psychiatric disorders such as anxiety. We have previously demonstrated the anxiolytic-like effect of Gamma oryzanol (GORZ) in chronic restraint stressed mice.Objective: We studied the neurochemical and molecular mechanisms that underlie the preventive effect of GORZ in HFD-induced anxiety-like behaviors, monoaminergic dysfunction, and inflammation.Methods: Eight-week-old Institute of Cancer (ICR) male mice weighing 33-34 g were divided into the following groups and free-fed for 8 weeks: control (14% casein, AIN 93M); HFD; HFD + GORZ (0.5% GORZ). Body weight gain was checked weekly. The anxiolyticlike effects of GORZ were examined via open-field test (OFT) and elevated plus maze (EPM) test. Brain levels of monoamines [5-hydroxy tryptamine (5-HT), dopamine (DA), and norepinephrine (NE)] and their metabolites [5-hydroxyindole acetic acid (5-HIAA), homovanillic acid (HVA), and 3-methoxy-4-hydroxyphenylglycol (MHPG)], proinflammatory cytokines such as tumor necrosis factor-aa (Tnf-a) mRNA levels, and interleukin 1-b (Il-1b) mRNA levels in the cerebral cortex and amygdala were examined using high-performance liquid chromatography-electrochemical detection (HPLC-ECD), and real-time reverse transcription-polymerase chain reaction (RT-PCR), respectively.Results: Mice fed a HFD for eight weeks showed anxiety-like behaviors in association with HFD-induced body weight gain. GORZ potentially blocked HFD-induced anxiety-like behaviors via significant improvement of the primary behavioral parameters in behavioral tests, with a minor reduction in HFD-induced body weight gain. Furthermore, GORZ treatment significantly downregulated HFD-induced upregulation of dopamine levels in the brain's amygdala. Significant reduction of the relative mRNA expression of Tnf-a and Il-1 b was also observed in the amygdala of HFD + GORZ mice, compared to HFD mice. Conclusions:Our findings strongly suggest that 0.5% GORZ exerts anxiolytic-like effects, possibly through downregulation of dopamine, and via expression of proinflammatory cytokines Tnf-a and Il-1 b in the case of chronic HFD exposure.
Adolescent alcohol exposure may increase anxiety-like behaviors by altering central monoaminergic functions and other important neuronal pathways. the present study was designed to investigate the anxiolytic effect of 0.5% γ-oryzanol (GORZ) and its neurochemical and molecular mechanisms under chronic 10% ethanol consumption. Five-week-old ICR male mice received either control (14% casein, AIN 93 M) or GORZ (14% casein, AIN 93 M + 0.5% GORZ) diets in this study. We showed that GORZ could potentially attenuate alcohol-induced anxiety-like behaviors by significantly improving the main behavioral parameters measured by the elevated plus maze test. Moreover, GORZ treatment significantly restored the alcohol-induced downregulation of 5-hydroxytryptophan and 5-hydroxyindole acetic acid in the hippocampus and improved homovanillic acid levels in the cerebral cortex. Furthermore, a recovery increase in the level of 3-methoxy-4-hydroxyphenylglycol both in the hippocampus and cerebral cortex supported the anxiolytic effect of GORZ. The significant elevation and reduction in the hippocampus of relative mRnA levels of brain-derived neurotrophic factor and interleukin 1β, respectively, also showed the neuroprotective role of GORZ in ethanol-induced anxiety. Altogether, these results suggest that 0.5% GORZ is a promising neuroprotective drug candidate with potential anxiolytic, neurogenic, and anti-neuroinflammatory properties for treating adolescent alcohol exposure. The high prevalence of alcohol exposure among adolescents is an important issue for public health 1-3 worldwide. Chronic ethanol consumption during adolescence may alter the risk/reward assessment and damage the developing brain, leading to an increase in impulsivity 4. Furthermore, underage drinking may also increase major depression risk and anxiety disorders 5,6 later in life. In addition, central nervous monoaminergic functions are altered after adolescent ethanol exposure 7-10 and may lead to neurological changes that reduce a person's normal fear of the consequences of their actions, and contribute to risk-taking or violent behaviors. The brain is more vulnerable to alcohol during growth and development, and many studies consistently show that teens with drinking alcohol are more likely to experience alcohol-related health problems, such as obesity, diabetes, liver and heart diseases, dementia and some forms of cancer, later in life than teens who abstain. The most commonly used medicines for patients with mood and anxiety disorders exert their effects by modifying monoaminergic neurotransmission. In particular, selective serotonin reuptake inhibitors (SSRIs) target the serotonergic system and block the reuptake of serotonin from the synaptic cleft by inhibiting the serotonin transporter and enhancing the amount of free serotonin available. Notably, there is molecular, physiological, and clinical evidence suggesting that the serotonergic system plays pivotal role in the neural circuitry of mood and anxiety disorders 11-13. The functional and structural chang...
The microbial activity of ten selected Azospirillum isolates was measured in terms of the amount of CO 2 evolved by the isolates after incubation for 5 days which ranged from 6.88 to19.25 mg. Nitrogen fixing efficiency all of the isolates was determined by microkjeldhal method and the nitrogen fixing efficiency ranged from 10.03 to 13.11 mg N/g substrate. The growth of Azospirillum isolates was significant affected by different physiological factors such as pH, temperature and salinity. Most of the isolates showed optimum growth at pH 6.8, temperature 37°C and in the absence of NaCl. Azospirillum has the potential to be used as a substitute and or supplement of N-fertilizers. Further research is needed to estimate N-supplement potentials of biological nitrogen fixation (BNF) systems at the farm level.
For just about 30 years, researchers have considered the likelihood to utilize nucleic acids as antiviral therapeutics. In principle, small single-stranded nucleotide sequence (oligonucleotide) could hybridize to a particular gene or messenger RNA and diminish transcription or translation, respectively, in this manner decreasing the amount of protein that is synthesized. Until now, an incredible number of antisense oligonucleotides, double-stranded oligonucleotides, aptamers, ribozymes, deoxyribozymes, interfering RNAs, chimeric RNA-DNA molecules, antibody genes has been created artificially and applied effectively for comprehension and manipulating biological processes and in clinical preliminaries to treat a variety of diseases. Their versatility and potency make them similarly fit candidates for fighting viral infections. However, troubles with their efficiency, off-target effects, toxicity, delivery, and stability halted the development of nucleic acid-based therapeutics that can be utilized in the clinic. The potential for nucleic acid therapeutic agents is significant and is quite recently beginning to be realized. In this review, we have summarized some of the recent advancements made in the area of nucleic acid based therapeutics and focused on the methods of their delivery and associated challenges.
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