Central MOTS-c infusion affects reproductive hormones in obese and non-obese rats.

MOTS-c, a mitochondrial-derived peptide, acts as a systemic hormone and MOTS-c level is inversely correlated with markers of obesity. Obesity is a risk factor for male reproductive physiology and is expressed as an important cause of infertility. In this study, we aimed to determine the effects of MOTS-c, which has been proven in the hypothalamus and testicles, on the actors involved in the reproductive axis. In the study, 80 male Wistar-Albino rats were divided into two main groups, obese and non-obese (n = 40). Rats in the first main group were fed with fatty diet feed and obesity was induced. The second main group was fed with normal diet feed. Each main group was divided into 4 subgroups (Control, Sham, 10 and 100 µM MOTS-c). The lateral ventricles of the animals in the treatment groups were infused with 10 and 100 µM MOTS-c (solvent in Sham group) for 14 days. At the end of the experiment, hypothalamic Gonadotropin-Releasing Hormone (GnRH) gene expression level, serum testosterone, Luteinizing hormone (LH) and Follicle stimulating hormone (FSH) levels were determined. MOTS-c infusion caused an increase in GnRH mRNA, protein expression levels and serum testosterone, LH and FSH levels in obese and non-obese rats (p < 0.05). MOTS-c administration more significantly upregulated hormone levels in non-obese rats (p < 0.05). MOTS-c administration increases these hormones, suggesting that MOTS-c may stimulate the reproductive axis. Our results reveal that MOTS-c plays a role in the central regulation of reproduction, as well as causes increased LH, FSH and testosterone release.

New Azo Derivative of ß-Diketones and Its Cu(II), Co(II) Complexes: Synthesis, Theoretical Study and Biological Activity.

The paper is focused on biological activity and theoretical study of the structure and properties of a new azo derivative of ß-diketones and its complexes with some metals. The aim of our work was to study the structure and properties of the newly synthesized compound as well as to theoretically determine the possibility of complex formation with the Cu(II) or Co(II) ions. A compound with the same substituents R1=R2=CH3 was chosen for the study. A synthesized azo compound based on 4-amino antipyrine and its complexes with Cu(II), Co(II) in solution and solid phase is reported. The structures of these compounds have been testified by X-ray, IR and  NMR spectroscopy. The combined experimental and theoretical approach was used. To study the structure and properties of the synthesized compound, as well as its possible complex formation with the Cu(II), quantum-chemical calculations were carried out the 6-31G basis set and the electron density functional theory (DFT) method. These 3-(1-phenyl-2,3-dimethyl-pyrazolone-5) azopentadione-2,4 (PDPA) with Cu(II) and Co(II) complexes had effective inhibition against butyrylcholinesterase and acetylcholinesterase. IC50 values were found as 19.03, 3.64 µM for AChE and 28.47, 8.01 µM for BChE, respectively. Cholinesterase inhibitors work to slow down the acetylcholine's deterioration.

Novel complex compounds of nickel with 3-(1-phenyl-2,3-dimethyl-pyrazolone-5)azopentadione-2,4: synthesis, NBO analysis, reactivity descriptors and in silico and in vitro anti-cancer and bioactivity studies.

A synthesized azo compound based on 4-amino antipyrine and its complexes with Ni(II) in solution and solid phase is reported. The structures of these compounds have been testified by IR and NMR spectroscopy. The combined experimental and theoretical approach was used. To study the structure and properties of the synthesized compound, as well as its possible complex formation with the Ni(II), ab initio quantum-chemical calculations were carried out using the Hartree-Fock (HF) method with the 6-31 G basis set and the electron density functional theory (DFT) method with hybrid three-parameter potential B3LYP and extended basis set 6-311++G(d,p) taking into account polarization and diffuse functions for all atoms. The geometric, energy, and electronic parameters were calculated and analyzed. The HOMO-LUMO energy gap has been calculated to determine chemical activity. Both complexes had effective inhibition against butyrylcholinesterase and acetylcholinesterase. IC50 values were found as 19.43 and 27.08 µM for AChE, 2.37 and 7.40 µM for BChE, respectively. For the anticancer outcome, high doses of compound E1 inhibited viability by about 40-45%, while this rate was around 65-70% for compound E2 at the same doses. Anticholinesterase and anticancer potential of compounds E1 and E2 also evaluated by in silico techniques. Both compounds show strong binding to VEGFR1, with E2 exhibiting superior inhibitory activity in hAChE and hBChE through shorter and stronger interactions. MD simulations suggest that E2 forms more stable complexes with hAChE and hBChE compared to E1, making it a promising candidate for further exploration in anticancer and anticholinesterase therapies.Communicated by Ramaswamy H. Sarma.

Biological Effects and Crystal X-Ray Study of Novel Schiff Base Containing Pentafluorophenyl Hydrazine: In Vitro and in Silico Studies.

A novel Schiff base namely 3,5-di-tert-butyl-6-((2-(perfluorophenyl)hydrazono)methyl)phenol was successfully synthesized and characterized using FT-IR and 1 H-NMR, 13 C-NMR, and 19 F-NMR. The crystal structure analysis of the Schiff base compound was also characterized with single crystal X-ray diffraction studies and supported the spectroscopic results. The cytotoxicity, anti-bacterial properties, and enzyme inhibition of the compound were also investigated. The molecular docking studies were performed in order to explain the interactions of the synthesized compound with target enzymes. The newly synthesized hydrazone derivative Schiff base compound showed high cellular toxicity on MCF-7 and PC-3 cells. Also, this compound caused low antibacterial effect on E. coli and S. aureus. Besides, the compound exhibited the inhibitory effect against pancreatic cholesterol esterase and carbonic anhydrase isoenzyme I, II with IC50 values 63, 99, and 188 µM, respectively. Consequently, it has been determined that the prepared Schiff base is an active compound in terms of cytotoxicity, enzyme inhibition, and anti-bacterial properties. These results provide preliminary information for some biological features of the compound and can play a major role in drug applications of the Schiff base compound.

Novel tetrakis-phthalocyanines bearing pyrimidine derivative: crystal XRD analysis, enzyme inhibition, molecular docking, and anticancer effects.

In this study, the novel 4-(4-Aminopyrimidin-2-ylthio) phthalonitrile (1) as starting material was synthesized and its 3D structure was verified by the single crystal X-ray diffraction experiment. Then, its peripherally tetra-substituted phthalocyanines (2,3) and the methylated derivatives (2a,3a) containing pyrimidine derivative were synthesized. All these newly synthesized compounds were characterized with various spectroscopic methods such as UV-Vis, FT-IR, 1H-NMR, 13C-NMR and MALDI-TOF MS by obtaining satisfactory results. In addition, these novel phthalocyanines effectively inhibited acetylcholinesterase enzyme, with Ki values in the range of 10.43 ± 2.38 to 41.70 ± 9.32 µM. For the related enzyme, the IC50 values were obtained in the range of 11.68 to 44.28 µM. For α-glycosidase enzyme the most effective Ki values of (3a) and (2) were with Ki values of 92.87 ± 10.70 and 95.18 ± 17.83 µM, respectively. Indeed, the most potent phthalocyanines against both enzymes were recorded for the purpose of investigating interaction modes of these complexes in the active site of the target enzyme. The cytotoxicity potential of these phthalocyanines against human breast, colon, and prostate cancers demonstrated that these compounds had normal cytotoxic effects.Communicated by Ramaswamy H. Sarma.

Evaluation of metabolic stress status in common carp (Cyprinus carpio) exposed to the fungicide folpet.

Among pesticides, fungicides are the most extensively used ones in agriculture and their effects on fish health and indirectly human health are needed to evaluate. Folpet has been used for over 50 years as a fungicide across the world. The mechanism of action of folpet on non-target aquatic organisms is so poorly understood and there is no available information about potential acute toxicity of folpet and its mechanism of action in non-target aquatic organisms. With this motivation, two successive experiments were set up: first, 96 h-LC50 value of folpet for common carp (Cyprinus carpio) was determined; and second, effects of different sublethal concentrations (0, 0.025, 0.50, 0.1 and 0.15 mg/L) of folpet on hematological serum biochemical blood parameters, DNA damages, expression levels of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione S-transferase (GST), and cortisol receptor (HSP70) genes were evaluated in this study. It was calculated that 0.199 mg/L of folpet was the 96 h-LC50 value. After the folpet exposure for 14 days, significant decreases in red blood cells, hemoglobin, hematocrit, serum total protein, and GST gene expression levels were observed while serum glucose, liver enzymes activities, and expression levels of CAT, SOD, GPx, HSP70 genes increased. Also, folpet induced a significant genotoxic effect on the blood cells regarding to DNA damages. Consequently, the results have shown the toxic effects of folpet even at the lowest concentration on common carp.

Mercury toxicity affects oxidative metabolism and induces stress responsive mechanisms in wheat (Triticum aestivum L.).

Mercury (Hg) toxicity is an increasing problem worldwide, with a negative impact on the environment and living organisms including both animals and plants. In this study, we analyzed molecular and biochemical changes related to Hg toxicity in wheat (Triticum aestivum L.) seedlings. Seven-day-old seedlings were exposed to various concentrations (5, 10, and 20 µM) of HgCl2 for 24 and 48 h. Our results showed that HgCl2 treatments led to an increase in the Hg content of wheat leaves in a time- and concentration-dependent manner. Furthermore, significant increases were observed in hydrogen peroxide, malondialdehyde, and proline contents in response to Hg toxicity. While all HgCl2 treatments decreased the level of superoxide dismutase (SOD), the level of catalase (CAT) was reduced only in seedlings exposed to 5 µM of HgCl2. Mercury stress caused a decline in the expression of Cu/Zn-SOD, Fe-SOD, TaWRKY19, and TaDREB1 genes at both exposure times. On the other hand, 10 and 20 µM HgCl2 treatments caused significant induction (1.9 to 6.1-fold) in the expression of the CAT gene in wheat leaves. The mRNA level of the Mn-SOD and TaWRKY2 genes showed different patterns depending on the concentration and exposure period of HgCl2. In conclusion, the findings of this work demonstrate that Hg toxicity causes oxidative damage in wheat seedlings and changes the expression of some genes encoding WRKY and DREB transcription factor families, which have important functions in abiotic stress response.

Effects of meteorin-like hormone on endocrine function of hypothalamo-hypophysial system and peripheral uncoupling proteins in rats.

BACKGROUND: Meteorin-like hormone (Metrnl) is a peptide secreted from the adipose tissue and modulates the whole-body energy metabolism. Metrnl release into the circulation is influenced by obesity, cold exposure, and exercise. Thyroid hormones also exert many of their effects on metabolism through uncoupling proteins (UCPs). This study aimed to determine effect of Metrnl on hypothalamo-hypophysier-thyroid axis and energy metabolism and reveal the possible involvement of UCPs in this process. METHODS AND RESULTS: Fourty male Sprague-Dawley rats were divided into 4 groups with 10 animals in each group: control, sham, 10 and 100 nM Metrnl. Hypothalamus, muscle, white adipose tissue (WAT) and brown adipose tissue (BAT) samples were collected to detect thyrotropin-releasing hormone (TRH), and UCP1 and UCP3 protein levels by western blot analysis. Serum thyroid-stimulating hormone (TSH), triiodothyronine (T3) and thyroxine (T4) hormone levels were determined by enzyme-linked immunosorbent assay. Central infusion of Metrnl caused significant increase in serum TSH, T3 and T4 levels compared to control (p < 0.05). After Metrnl treatment, there were significant increases in TRH in hypothalamus tissue, UCP1 in WAT and BAT; and UCP3 protein in the muscle tissue (p < 0.05). CONCLUSIONS: The findings that Metrnl induced increases in the peripheral UCPs and hypothalamus-pituitary-thyroid axis hormones implicate a role for this hormone in body energy homeostasis through UCP-mediated mechanisms.

Metal contained Phthalocyanines with 3,4-Dimethoxyphenethoxy substituents: their anticancer, antibacterial activities and their inhibitory effects on some metabolic enzymes with molecular docking studies.

The compounds (3-6) used in this study were re-synthesized in accordance with our previous study. The inhibitory effect of the complexes on some metabolic enzymes was examined and it was demonstrated that the enzymes inhibited by ligands and their complex molecules at micromolar level. The best Ki value for α-glycosidase enzyme was absorved 1.01±0.08 µM for compound 6. The biological activity of ligand and metal complexes against enzymes was compared with molecular docking method. The enzymes used against ligand and metal complexes respectively: Achethylcholinesterase for ID 4M0E (AChE), butyrylcholinesterase for ID 5NN0 (BChE), α-glycosidase for ID 1XSI (α-Gly). ADME analysis was performed to examine the drug properties of the compounds (3-6). Besides, the anticancer properties of the complexes were studied. The doses of all compounds caused significant reductions in MCF-7 cell viability. The 3 and 5 compounds administered to PC-3 cells exhibited a more pronounced cytotoxic effect than the other two compounds (4 and 6). Furthermore, antibacterial activities of these compounds against Escherichia coli and Staphylococcus aureus were examined.Communicated by Ramaswamy H. Sarma.

Protective effect of saxagliptin against renal ischaemia reperfusion injury in rats.

Saxagliptin is an effective and selective dipeptidyl peptidase-4 (DPP-4) inhibitor. This study was designed to determine possible protective effects of saxagliptin against damage caused by renal ischaemia/reperfusion (I/R) in rats. In this study, 40 rats were divided into 4 groups (n = 10 for each). Group 1 (Control), Group 2 (I/R) in both kidneys ischaemia of 45 min was performed, and then reperfusion was applied for 24 h. Saxagliptin (Group 3: 2 mg/kg and Group 4: 10 mg/kg) was administered by oral gavage to the animals in treatment groups, before the I/R. Saxagliptin decreased the markers (BUN, Cre, NGAL, KIM-1 and IL-18) of acute renal damage in blood and kidney tissue. Saxagliptin provided increase in antioxidant enzyme levels and decrease in MDA and apoptosis. Histological results showed that the administration of saxagliptin exhibited a protective effect against renal damage caused by I/R. These results indicates that saxagliptin provide protection against kidney injury caused by I/R.

Intracerebroventricular asprosin administration strongly stimulates hypothalamic-pituitary-testicular axis in rats.

Asprosin, a protein-based secretary product of white adipose tissue, stimulates appetite hepatic glucose production. It crosses blood-brain barrier and stimulates appetite center and causes sperm chemotaxis but exact role of this endogenous agent is not completely known. This study was conducted to investigate possible effects of central asprosin infusion on the hormones involved in the hypothalamic-pituitary-testicular (HPT) axis and sperm cells. Spraque Dawley male rats were divided into four groups; control, sham, low asprosin (34) and high asprosin (68 nM) groups, (n = 10 for each group). Control group remain intact while a brain infusion kit was placed in the lateral ventricles of the rats in the sham group (artificial cerebrospinal fluid) and asprosin (34 and 68 nM) was infused for 14 days. At the end of the experiment, the hypothalamus, blood, and epididymis tissues of the rats were collected. Gonadotropin-releasing hormone (GnRH) mRNA and tissue protein levels were determined in the hypothalamus tissue by RT-PCR and Western Blot methods. Serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone levels were examined using the ELISA method from blood samples and sperm cells were examined in the epididymis tissue. GnRH mRNA and protein expressions of asprosin administered groups were higher than control and sham groups (p < 0.05). Asprosin infusion was also found to increase serum FSH, LH, and testosterone levels (p < 0.05). In addition, sperm density, motility, and progressive movement were observed to increase in asprosin administered groups (p < 0.05). This study suggests that central asprosin stimulate the HPT axis and also epididymis tissue. Our results implicates potential role for asprosin in male infertility.

Design, synthesis, characterization, enzymatic inhibition evaluations, and docking study of novel quinazolinone derivatives.

In this study, novel quinazolinone derivatives 7a-n were synthesized and evaluated against metabolic enzymes including α-glycosidase, acetylcholinesterase, butyrylcholinesterase, human carbonic anhydrase I, and II. These compounds exhibited high inhibitory activities in comparison to used standard inhibitors with Ki values in the range of 19.28-135.88 nM for α-glycosidase (Ki value for standard inhibitor = 187.71 nM), 0.68-23.01 nM for acetylcholinesterase (Ki value for standard inhibitor = 53.31 nM), 1.01-29.56 nM for butyrylcholinesterase (Ki value for standard inhibitor = 58.16 nM), 10.25-126.05 nM for human carbonic anhydrase I (Ki value for standard inhibitor = 248.18 nM), and 13.46-178.35 nM for human carbonic anhydrase II (Ki value for standard inhibitor = 323.72). Furthermore, the most potent compounds against each enzyme were selected in order to evaluate interaction modes of these compounds in the active site of the target enzyme. Cytotoxicity assay of the title compounds 7a-n against cancer cell lines MCF-7 and LNCaP demonstrated that these compounds do not show significant cytotoxic effects.

Determination of anticancer properties and inhibitory effects of some metabolic enzymes including acetylcholinesterase, butyrylcholinesterase, alpha-glycosidase of some compounds with molecular docking study.

Inhibitory effect of the complexes on some metabolic enzyme demonstrated that the enzymes inhibited by ligand and it's complex molecules at the micromolar level. The best inhibition effect for α-glycosidase (α-Gly) enzyme against cobalt complex with Ki value of 3.77 ± 0.58 µM. For achethylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes against SM-Co complex, Ki values of 74.23 ± 5.02 µM and 101.21 ± 12.84 µM Ki were observed, respectively. Molecular docking studies were performed to compare the biological activities of ligands and ligand complexes against enzymes whose names are AChE for ID 4M0E, BChE for ID 5NN0, α-Gly for ID 1XSI respectively. Also, anticancer properties of the complexes studied. The doses of all compounds caused significant reductions in MCF-7 cell viability. Zr compound showed the best cytotoxic activity against the MCF-7 cell. SM ligand administered to PC-3 cells exhibited a more pronounced cytotoxic effect than the SM-Co and Zr compounds.Communicated by Ramaswamy H. Sarma.

Capsanthin Stimulates the Mitochondrial Apoptosis-Mediated Cell Death, following DNA Damage in MCF-7 Cells.

Carotenoids found in fruits and vegetables are compounds with significant biological activities. Epidemiological studies report that these compounds have significant anticancer effects, as well reducing the risk of cancer. In the present study, we aimed to determine the effects of capsanthin, an important carotenoid of paprika, on expressions of proteins playing roles in the mitochondrial apoptosis pathway, in addition to its possible cytotoxic and genotoxic effects in MCF-7 cells. Furthermore, possible oxidant/anti-oxidant roles of capsanthin on MCF-7 cells were investigated. The viability of MCF-7 cells was significantly decreased after 24 h of capsanthin application. After Comet analysis, it was determined that the capsanthin caused DNA damage on a dose-dependent manner. Furthermore, Western blot analysis showed that capsanthin application increased p53 and Bax protein expressions and caused a decrease in Bcl-2 protein level. Capsanthin treatment decreased catalase and glutathione levels but increased lipid peroxidation. These results show that the capsanthin causes oxidative stress and DNA damage, and increases mitochondrial apoptotic mechanism-mediated cell death after p53 and Bax protein activations.

The biological activities, molecular docking studies, and anticancer effects of 1-arylsuphonylpyrazole derivatives.

This work is devoted to definition of the direction of reaction between 1-benzenesulfonylimino pyridinium chloride and α- or ß-halo-containing sulfamides, chloroacetic acid, 1-chloro-2,3-dihydroxypropane, etc. The optimal conditions for the synchronous reaction of heterocyclization are determined. Benzenesulfonyliminopyridinium chloride was obtained to form pyrazolopyridines with 1,2-polarophiles, and pyridazine pyridines with 1,3-polarophiles. These novel derivatives were found as effective inhibitors of the α-glycosidase with Ki values in the range of 13.66 ± 2.63-60.63 ± 12.71 nM. The molecules (II-X) against enzyme were compared theoretically with the help of molecular docking to compare biological activities. The results were compared with the numerical values of the parameters obtained from molecular docking calculations and found to be in great agreement with the experimental results. However, ADME analysis of molecules was performed. Also, the compounds exhibited significant anticancer effect depending on the doses administered.Communicated by Ramaswamy H. Sarma.

Cytotoxic effects, carbonic anhydrase isoenzymes, α-glycosidase and acetylcholinesterase inhibitory properties, and molecular docking studies of heteroatom-containing sulfonyl hydrazone derivatives.

Today, interest in studies on the search for new drugs to be used in diseases such as cancer, cardiovascular diseases, neurodegenerative diseases and diabetes, as well as prevention of microbial inflammation is increasing day by day. Emerging biological and pharmacological effects of sulfonyl hydrazone derivative compounds reveal their importance. In the present study, heteroatom-containing sulfonyl hydrazone derivatives have been studied for their anticancer and antimicrobial properties, as well as their effects on enzymes that could play roles in Alzheimer's dissease and diabetes. High doses of the tested compounds significantly decreased the cell viabilities of breast cancer (MCF-7) and prostate cancer (PC-3) cell lines. Furthermore, all compounds possessed antimicrobial activities against very common bacteria E. coli and S. aureus. These compounds were good inhibitors of the α-glycosidase, human carbonic anhydrase I and II isoforms and acetylcholinesterase enzyme with Ki values in the range of 1.14 ± 0.14-3.63 ± 0.26 nM for α-glycosidase, 66.05 ± 9.21-125.45 ± 11.54 nM for hCA I, 89.14 ± 10.43-170.22 ± 26.05 nM for hCA II and 754.03 ± 73.22-943.92 ± 58.15 nM for AChE, respectively. Molecular docking method was used to theoretically compare biological activities of sulfonyl hydrazone derivatives against enzymes. The theoretical results were compared with the experimental results. Thus, these compounds have strong biological activities.Communicated by Ramaswamy H. Sarma.

Novel tribenzylaminobenzolsulphonylimine based on their pyrazine and pyridazines: Synthesis, characterization, antidiabetic, anticancer, anticholinergic, and molecular docking studies.

A new method of obtaining multifunctional pyrazoles by the reaction of 1,3-dipolar addition of tribenzylsulfonyliminochloride to polarophiles has been developed. This imine is obtained by reacting tribenzylamine with N-chlorobenzene sulfamide (chloramine-B). Regardless of the structure and composition of polarophiles, the cyclization reaction takes place in the presence of alkali in 6-8 h of boiling, which proves the activation of the methylene groups of tribenzylamine using the electron-withdrawing sulfonamide group. These novel derivatives were effective inhibitors of the α-glycosidase, butyrylcholinesterase (BChE), and acetylcholinesterase enzymes (AChE) with Ki values in the range of 0.45 ±â€¯0.08-1.24 ±â€¯0.27 µM for α-glycosidase, 6.04 ±â€¯0.95-11.61 ±â€¯2.84 µM for BChE, and 2.04 ±â€¯0.24-4.23 ±â€¯1.02 µM for AChE, respectively. The biological activities of the studied molecules against enzyme molecules were investigated by molecular docking calculations. The enzymes studied were AChE for ID 4M0E, BChE for ID 5NN0 BChE, and α-Glycosidase for ID 1XSI (α-Gly) respectively.

Effects of intracerebroventricular administration of irisin on the hypothalamus-pituitary-gonadal axis in male rats.

Irisin is a product of fibronectin type III domain-containing protein 5 (FNDC5) and plays an important role in energy homeostasis. In this study, we aimed to determine effects of intracerebroventricular administration of irisin on the hypothalamus-pituitary-gonadal axis by molecular, biochemical, and morphological findings. Fourty male Wistar-Albino rats were used and divided into four groups including control, sham (vehicle), 10, and 100 nM irisin infused groups (n = 10). Hypothalamic gonadotropin releasing hormone (GnRH) level and serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone levels were determined. Testicular tissue histology and spermiogram analysis were also performed. Both irisin concentrations significantly reduced hypothalamic GnRH messenger RNA (mRNA) and protein levels (p < 0.05). It was found that serum LH, FSH, and testosterone levels and Sertoli and Leydig cell numbers were decreased by irisin administration (p < 0.05). In addition, irisin administration reduced sperm density and mobility (p < 0.05). However, it did not cause any change in testicular and epididymis weights and tubular diameter. Our results reveal that irisin can play a role in the central regulation of reproductive behavior and also reduces testosterone levels by suppressing LH and FSH secretion. These results suggest that the discovery of irisin receptor antagonists may be beneficial in the treatment of infertility.

Cannabinoid type 2 receptor agonist JWH-133, attenuates Okadaic acid induced spatial memory impairment and neurodegeneration in rats.

AIM: Cannabinoid system has various physiological roles such as neurogenesis, synaptic plasticity and emotional state regulation in the body. The presence of cannabinoid type 2 receptor (CB2), a member of the cannabinoid system, was detected in different regions of the brain. CB2 receptor plays a role in neuroinflammatory and neurodegenerative processes. We aimed to determine the possible effect of CB2 agonist JWH-133 in Okadaic acid (OKA)-induced neurodegeneration model mimicking Alzheimer's Disease (AD) through tau pathology. MATERIALS AND METHODS: In this study, 40 Sprague Dawley male rats were divided into 4 groups (Control, Sham, OKA, OKA + JWH-133). Bilateral intracerebroventricular (icv) injection of 200 ng OKA was performed in the OKA group. In the OKA + JWH-133 group, injection of JWH-133 (0.2 mg/kg) was performed intraperitoneally for 13 days different from the group of OKA. Morris water maze test was used to evaluate the spatial memory. Levels of caspase-3, phosphorylated tau (ser396), amyloid beta (Aß), tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1ß) levels in brain cortex; and the hippocampus regions were examined by immunohistochemical methods. KEY FINDINGS: In the OKA group, caspase-3, phosphorylated tau (ser396), Aß, IL-1ß levels were higher in the cortex and hippocampus than in the other groups. The implementation of the JWH-133 reversed the increments in these parameters, and also prevented spatial memory impairment. SIGNIFICANCE: In this study, we found that the administration of the CB2 receptor agonist JWH-133 in this study reduced neurodegeneration, neuroinflammation, and spatial memory impairment in the OKA-induced Alzheimer's Disease model.

Central irisin administration suppresses thyroid hormone production but increases energy consumption in rats.

Irisin, which is secreted from the skeletal muscle in response to physical exercise and defined as a thermogenic peptide, may play an important role in energy metabolism. Thyroid hormones, which are one of the other influential factors on the metabolic status, increase heat production and are the main regulators of energy metabolism. This study was conducted to determine the possible effects of irisin administration on thyroid hormones. Forty adult male Wistar albino rats were used in the study. The rats were equally divided into 4 groups (n = 10). The brain infusion kit was implanted in the groups, and irisin (or solvent as control) was centrally administered to the rats via osmotic mini pumps for 7 days. During the experiment, food consumption, body weights, and body temperatures of the animals were recorded. Food intake was significantly increased in the groups treated with irisin (p < 0.05), but their body weights were not changed. Hypothalamic TRH gene expression, serum TSH, fT3, and fT4 levels were significantly lower in the groups treated with irisin as compared to the naive and control groups (p < 0.05). In addition, irisin increased UCP1 mRNA expression in white and brown adipose tissue and UCP3 mRNA expression in muscle tissue in rats and also raised their body temperature (p < 0.05). Consequently, although central irisin administration has inhibitory effects on the hypothalamic-pituitary-thyroid axis, it seems to be an important agent in the regulation of food intake and energy metabolism.