Catestatin and GABAAR related feeding habits rely on dopamine, ghrelin plus leptin neuroreceptor expression variations

Catestatin (CST), an endogenously small sympathoinhibitory peptide is capable of interfering with the major cerebral neuroreceptor-blocking site, i.e. γ-aminobutyric acidA receptor (GABAAR) system especially in limbic brain areas that are involved with feeding behaviors. The GABAARergic-related effects seem to derive from its interaction with other molecular neuroreceptors such as dopaminergic, ghrelin and leptinergic. In this context, the present study aimed to investigate probable feeding responses (eating and drinking) induced by treatment with CST and the GABAAR antagonist bicucullin (BIC) alone or simultaneously (CST+BIC) in the Syrian hibernating hamster (Mesocricetus auratus) model. Hamsters that received these compounds via intracerebroventricular infusions displayed notable variations of feeding and drinking bouts. In particular, an anorexigenic response was evident following treatment with CST while BIC evoked a significant increase of eating and drinking behaviors. Surprisingly when both agents were given simultaneously, a predominating anorexigenic response was detected as shown by evident CST-dependent reduction of feeding bouts. Contextually such behaviors, especially those following the combined treatment were tightly correlated with the significantly increased cerebral dopamine receptor 1 (D1) plus reduced ghrelin receptor (GhsR) and leptin receptor (LepR) transcript levels. Overall, the anorexigenic effect of CST deriving from its tight interaction with GABAARs activity plus D1 and GhsR transcripts tends to propose these neuronal elements as pivotal factors responsible for feeding disorders

Effetti del daidzein sul comportamento mnemonico attraverso le variazioni del sistema neurotensinergico e di fattori infiammatori in aree limbiche di criceti high fat diet

Dottorato di Ricerca in Scienze della Vita. Ciclo XXXIn the past years, growing indications have pointed to food diets as major factors capable of conditioning physical-social states in humans as suggested by high-fat containing food sources which, despite their extremely "tasteful" properties, are responsible for marked morpho-structural alterations in critical brain areas for the regulation of not only psycho-cognitive behaviors but above all for nutritional parameters. It is already known that food consumption and action mechanisms implicated in energetic homeostasis are part of a complex neuronal circuit that when they are altered tend to account for increased body weight and consequently the development of obesity, regarded a chronic disease leading to different medical co-morbidities such as cardiovascular diseases (especially hypertension), dyslipidemia and diabetes type 2. From these effects plus the avoidance of applying drugs with numerous collateral alterations have directed a greater attention towards the production of "safer" drugs natural deriving vegetable extracts such as daidzein (DZ), a glucosidic isoflavone capable of mimicking estrogenic activities at the brain level, which supplied neuroprotective values against increased body weight, elevated feeding duration and diminished locomotor activity of high fat diet (HFD) hamsters (Mesocricetus auratus). This isoflavone also reduced anxiety-like behaviors in hyperlipidic animals as indicated by a greater time spent (p<0.01) in open arms of elevated plus maze (EPM) along with greater exploration (p<0.001) tendencies toward new objects of the novel object recognition (NOR) test. From a molecular point of view, DZ greatly protected the brain against neurodegeneration events as pointed out by few Amino Cupric Silver Stain granules in the hippocampus (HIP), hypothalamus (HTH) and amygdala (AMY) very likely via a diminished interaction of neurotensin receptor1 (anorexic neuropeptide; NTR1) GABAergic-leptin receptor levels in the latter two areas after the conditioned place preference (CPP) test. Contextually the recovered cognitive performances seemed to be tightly linked with reduced NTR1 expression levels in an ERβ manner for HIP after NOR test. In addition, such effects of DZ also strongly required increased levels of the antineuroinflammatory cytokine IL-10 that by reducing adenosine 5' monophosphate kinase (AMPK) and extracellular receptor kinase (ERK) widely improved cognitive together with exploratory behaviors. Overall, these first results supply important evidences on the neuroprotective values of DZ, which through NTR1 + IL-10 protective and repairing mechanisms of, aside the above limbic areas, also appetite-mediated brain centers known for their feeding, cognitive and endocrine functions, may surely comprise a good start for the introduction of novel therapeutic applications against obesity conditions.Università della Calabri

Cerebral pCREB-dependent social behavioral adversities following a short-term exposure to obesogenic diets in young hamsters

Excessive fat and sugar intake represents a risk towards the development of different pathologies, such as obesity, diabetes, sociability and memory deficits. Although the adolescence stage is a susceptible period for these and other risks, effects of energy-dense nutrients in such an age period have not been fully investigated. In the present study, neurobehavioral alterations following a 4-week exposure to either normal diet (ND) or high-fat diet (HFD) plus normal water (NW) or liquid sugar (LS) were evaluated in young hamsters. HFD + LS and ND + LS significantly reduced food intake and water consumption, which was, in the latter group, almost completely substituted by LS. All obesogenic diets accounted for increased abdominal fat and liver weight with respect to body weight (p &lt; 0.05–0.001). Additionally, glucose levels notably increased (p &lt; 0.0001) together with insulin and triglycerides in HFD + LS (p &lt; 0.001) and ND + LS (p &lt; 0.01) while cholesterol displayed only a moderate increase (p &lt; 0.05) in HFD + NW and HFD + LS. Animals fed with HFD and/or LS exhibited impaired social memory plus increased winning percentages (0.05 &lt; p &lt; 0.01) during the tube test. Interestingly, these same treatments led to a down-regulation of phosphorylated cAMP Response-Element Binding Protein (pCREB) in HFD + NW (p &lt; 0.0001) for all areas, but rather was upregulated (p &lt; 0.05) in ND + LS of the amygdala. Overall, in view of a brief exposure to palatable foods interfering with normal metabolic and social memory activities, the downregulation of pCREB constitutes a key indicator of neurobehavioral deficits during obesogenic diets. Compensatory mechanisms may be also occurring in the amygdala that strongly regulates emotional states via connections with other limbic areas