Hormone replacement therapy did not alleviate temporomandibular joint inflammatory pain in ovariectomized rats.

This study had the aim of examining the relationships between variations in estrogen levels resulting from ovariectomy, and estrogen hormone replacement therapy (HRT) in rats subjected to an orofacial inflammatory pain model. Eighty adult female Wistar rats were initially divided into 2 groups: Sham or ovariectomy (OVX-D1). Seven days later (D7), the rats were subjected to an unilateral infiltration of Freund's Complete Adjuvant (CFA) or saline solution into the right temporomandibular joint (TMJ). Then, rats received 17ß-estradiol (28 µg/kg/day) or placebo for 21 days (D10-D31). Nociception was evaluated by the von Frey (VF) and the Hot Plate (HP) tests, and depressive-like behavior by the Forced Swimming (FS) test. On D32 all rats were euthanized and serum, hippocampus and brainstem were collected. The CFA groups presented a mechanical hyperalgesia until day 21 (p ≤ 0.05). No differences were observed among groups in the HP (p = 0.735), and in the immobility and swimming time of the FS (p = 0.800; p = 0.998, respectively). In the brainstem, there was a significant difference in the TNF-ɑ levels (p = 0.043), and a marginal significant difference in BDNF levels (p = 0.054), without differences among groups in the hippocampal BDNF and TNF-ɑ levels (p = 0.232; p = 0.081, respectively). In conclusion, the hormone replacement therapy did not alleviate orofacial pain in ovariectomized rats. However, there is a decrease in brainstem TNF-ɑ levels in the animals submitted to both models, which was partially reverted by HRT.

Transcranial Direct Current Stimulation (tDCS) Promotes state-dependent Effects on Neuroinflammatory and Behavioral Parameters in rats Chronically Exposed to Stress and a Hyper-Palatable Diet.

Chronic stress is a common condition affecting health, often associated with unhealthy eating habits. Transcranial direct current stimulation (tDCS) has been proposed to address these issues. Thus, this research investigated the effects of tDCS on biometric, behavioral, and neurochemical parameters in chronically stressed rats fed a hyper-palatable cafeteria diet (CAFD). The study lasted 8 weeks, with CAFD exposure and/or chronic restraint stress model (CRS - 1 h/day, 5 days/week, for 7 weeks) started concurrently. tDCS or sham sessions were applied between days 42 and 49 (0.5 mA, 20 min/day). CAFD increased body weight, caloric consumption, adiposity, and liver weight. It also altered central parameters, reducing anxiety and cortical levels of IL-10 and BDNF. In turn, the CRS resulted in increased adrenals in rats with standard diet (SD), and anxiety-like and anhedonic behaviors in rats with CAFD. tDCS provided neurochemical shifts in CAFD-fed stressed rats increasing central levels of TNF-α and IL-10, while in stressed rats SD-fed induced a decrease in the adrenals weight, relative visceral adiposity, and serum NPY levels. These data demonstrated the anxiolytic effect of CAFD and anxiogenic effect of stress in CAFD-fed animals. In addition, tDCS promoted state-dependent effects on neuroinflammatory and behavioral parameters in rats chronically exposed to stress and a hyper-palatable diet. These findings provide primary evidence for additional mechanistic and preclinical studies of the tDCS technique for stress-related eating disorders, envisioning clinical applicability.

Nicotinamide riboside and dietary restriction effects on gut microbiota and liver inflammatory and morphologic markers in cafeteria diet-induced obesity in rats.

OBJECTIVES: No specific therapy is available for metabolic dysfunction-associated fatty liver disease. We investigated nicotinamide riboside (NR) and dietary restriction (DR) effects in liver lipids, inflammation, histology, intestinal permeability, and gut microbiota in a cafeteria diet (CAFD)-induced obesity model. METHODS: Adult male Wistar rats were randomly assigned to standard diet (SD) or CAFD. After 6 wk, they were subdivided into six groups-SD + vehicle (Veh) (distilled water), SD + NR (400 mg/kg), DR + Veh, DR + NR, CAFD + Veh, and CAFD + NR-for 4 wk more until euthanasia. RESULTS: CAFD increased the hepatic content of lipids, triacylglycerols, and total cholesterol and promoted hepatomegaly, steatosis, steatohepatitis, and liver fibrosis. DR intervention successfully delayed the onset of CAFD-induced liver abnormalities except for steatosis and fibrosis. CAFD suppressed Sirt1 expression in the liver and DR increased Sirt3 expression. CAFD did not affect hepatic inflammatory genes but DR enhanced Il10 expression while decreasing Il1ß expression. CAFD reduced Firmicutes and increased Bacteroidetes and Cyanobacteria, with no changes in intestinal permeability. Gut microbiota patterns in animals exposed to DR were similar to those of animals in SD. NR, specifically in CAFD, reduced hepatic triacylglycerols and total cholesterol deposition and collagen fiber accumulation in the liver and limited the colonization of CAFD-induced Cyanobacteria. NR combined with DR decreased the liver's relative weight and Tnfα expression and suppressed Sirt1 and Sirt3 hepatic expression. CONCLUSIONS: This study suggests that NR can be a potential adjuvant to metabolic dysfunction-associated fatty liver disease therapy, encouraging further research in this field.

Nicotinamide Riboside Neutralizes Hypothalamic Inflammation and Increases Weight Loss Without Altering Muscle Mass in Obese Rats Under Calorie Restriction: A Preliminary Investigation.

Obesity treatments, such as calorie restriction (CR), eventually lead to muscle wasting and higher rates of neuroinflammation, whereas hypothalamic inflammatory conditions impair body weight (BW) control. Nicotinamide riboside (NR) has been proposed against obesity but with little evidence on skeletal muscle tissue (SMT) and neuroinflammation. Therefore, we aimed to investigate the effects of CR on SMT and on hypothalamic inflammatory biomarkers in obese adult male Wistar rats, and whether NR supplementation alone or in combination with CR affects these parameters. Obesity was induced in rats through a cafeteria diet for 6 weeks. After that, a group of obese rats was exposed to CR, associated or not associated with NR supplementation (400 mg/kg), for another 4 weeks. As a result, obese rats, with or without CR, presented lower relative weight of SMT when compared with eutrophic rats. Rats under CR presented lower absolute SMT weight compared with obese and eutrophic rats, in addition to presenting elevated hypothalamic levels of TNF-α. NR supplementation, in all groups, enhanced weight loss and increased relative weight of the SMT. Furthermore, in animals under CR, NR reversed increases TNF-α levels in the hypothalamus. In this study, these data, although succinct, are the first to evidence the effects of NR on SMT and neuroinflammation when associated with CR, especially in obesity conditions. Therefore, this provides preliminary support for future studies in this investigative field. Furthermore, NR emerges as a potential adjuvant for preventing muscle mass loss in the weight loss processes.

Repetitive Transcranial Magnetic Stimulation (rTMS) Reverses the Long-term Memory Impairment and the Decrease of Hippocampal Interleukin-10 Levels, both Induced by Neuropathic Pain in Rats.

Neuropathic pain (NP) is characterized by the presence of spontaneous pain, allodynia and hyperalgesia. Repetitive transcranial magnetic stimulation (rTMS) is one of neuromodulatory techniques that induces satisfactory NP relief, including that from refractory pain patients. The objective of this study was to evaluate rTMS treatment over long term memory (LTM) and hippocampal BDNF and IL-10 levels in rats submitted to a NP model. A total of 81 adult (60-days old) male Wistar rats were randomly allocated to one of the following 9 experimental groups: control, control + sham rTMS, control + rTMS, sham neuropathic pain, sham neuropathic pain + sham rTMS, sham neuropathic pain + rTMS, neuropathic pain (NP), neuropathic pain + sham rTMS and neuropathic pain + rTMS. Fourteen days after the surgery for chronic constriction injury (CCI) of the sciatic nerve, NP establishment was accomplished. Then, rats were treated with daily 5-minute sessions of rTMS for eight consecutive days. LTM was assessed by the object recognition test (ORT) twenty-four hours after the end of rTMS treatment. Biochemical assays (BDNF and IL-10 levels) were performed in hippocampus tissue homogenates. rTMS treatment reversed the reduction of the discrimination index in the ORT and the hippocampal IL-10 levels in NP rats. This result shows that rTMS reverses the impairment LTM and the increase in the hippocampal IL-10 levels, both induced by NP. Moreover, it appears to be a safe non-pharmacological therapeutic tool since it did not alter LTM and neurochemical parameters in naive animals.

Nicotinamide riboside reduces cardiometabolic risk factors and modulates cardiac oxidative stress in obese Wistar rats under caloric restriction.

AIMS: NAD-based therapeutic strategies are encouraged against obesity and heart disease. Our study, therefore, aimed to investigate the effects of nicotinamide riboside (NR), isolated or combined with caloric restriction (CR), both approaches well-known for stimulating NAD levels, on adiposity parameters, cardiometabolic factors and cardiac oxidative stress in rats submitted to cafeteria diet (CAF). MAIN METHODS: After 42 days of CAF-induced obesity (hypercaloric and ultra-processed foods common to humans), we examined the effects of oral administration of NR (400 mg/kg for 28 days), combined or not with CR (-62% kcal, for 28 days), on anthropometric, metabolic, tissue, and cardiac oxidative stress parameters in obese male Wistar rats. KEY FINDINGS: In obese rats, treatment with NR alone mitigated final body weight gain, reduced adiposity (visceral and subcutaneous), improved insulin resistance, and decreased TG/HDL ratio and heart size. In cardiac OS, treatment with NR increased the antioxidant capacity via glutathione peroxidase and catalase enzymes (in rats under CR) as well as reduced the pro-oxidant complex NADPH oxidase (in obese and lean rats). Hyperglycemia, hypertriglyceridemia and elevated levels of TBARS in the heart were state-dependent adverse effects, induced by treatment with NR. SIGNIFICANCE: This is the first study to report effects of nicotinamide riboside on cardiac oxidative stress in an obesity model. Nicotinamide riboside, a natural dietary compound, presented antiobesity effects and cardiometabolic benefits, in addition to positively modulating oxidative stress in the heart, in a state-dependent manner.