Daidzein Pro-cognitive Effects Coincided with Changes of Brain Neurotensin1 Receptor and Interleukin-10 Expression Levels in Obese Hamsters.

At present, concerns are pointing to "tasteful" high-fat diets as a cause of conditioning physical-social states that through alterations of some key emotional- and nutritional-related limbic circuits such as hypothalamic and amygdalar areas lead to obesity states. Feeding and energetic homeostatic molecular mechanisms are part of a complex neuronal circuit accounting for this metabolic disorder. In an attempt to exclude conventional drugs for treating obesity, daidzein, a natural glycosidic isoflavone, which mimics estrogenic neuroprotective properties against increased body weight, is beginning to be preferred. In this study, evident anxiolytic-like behaviors were detected following treatment of high-fat diet hamsters with daidzein as shown by extremely evident (p < 0.001) exploration tendencies in novel object recognition test and a notably greater amount of time spent (p < 0.01) in open arms of elevated plus maze. Moreover, the isoflavone promoted a protective role against neurodegeneration processes as shown by few, if any, amino cupric silver granules in amygdalar, hypothalamic and hippocampal neuronal fields when compared with obese hamsters. Interestingly, elevated expression levels of the anorexic neuropeptide receptor neurotensin1 in the above limbic areas of obese hamsters were extremely reduced by daidzein, especially during recovery of cognitive events. Contextually, such effects were strongly paralleled by increased levels of the anti-neuroinflammatory cytokine, interleukin-10. Our results corroborate a neuroprotective ability of this natural glycosidic isoflavone, which through its interaction with the receptor neurotensin1 and interleukin-10 pathways is correlated not only to improved feeding states, and subsequently obesity conditions, but above all to cognitive performances.

Genistein Modifies Hamster Behavior and Expression of Inflammatory Factors following Subchronic Unpredictable Mild Stress.

BACKGROUND: Previous studies have pointed to the protective role of genistein against stress adaptations although neuromolecular mechanisms are not yet fully known. With this work, we evaluated the influence of such a phytoestrogen on hamster behavioral and molecular activities following exposure to subchronic unpredictable mild stress. METHODS: The motor behaviors of hamsters (n = 28) were analyzed using elevated plus maze (EPM) test, hole board (HB) test, and forced swim test (FST). In addition, neurodegeneration events were assessed with amino cupric silver stain, while expression variations of tropomyosin receptor kinase B (TrkB), nuclear factor kappa-B1 (NF-κB1), and heat shock protein 70 (Hsp70) mRNAs were highlighted in limbic neuronal fields via in situ hybridization. RESULTS: Genistein accounted for increased motor performances in EPM and HB tests but reduced immobility during FST, which were correlated with diminished argyrophilic signals in some limbic neuronal fields. Contextually, upregulated Hsp70 and TrkB mRNAs occurred in hippocampal (HIP) and hypothalamic neuronal fields. Conversely, diminished NF-κB1 levels were mainly obtained in HIP. CONCLUSION: Hormonal neuroprotective properties of genistein corroborating anxiolytic and antidepressant role(s) through elevated expression levels of stress proteins and trophic factors may constitute novel therapeutic measures against emotional and stress-related motor performances.

Application of the Co-culture Membrane System Pointed to a Protective Role of Catestatin on Hippocampal Plus Hypothalamic Neurons Exposed to Oxygen and Glucose Deprivation.

Depletion of oxygen and glucose even for brief periods is sufficient to cause cerebral ischemia, which is a predominant worldwide cause of motor deficits with the reduction of life quality and subsequently death. Hence, more insights regarding protective measures against ischemic events are becoming a major research goal. Among the many neuronal factors, N-methyl-D-aspartate receptors (NMDAR), orexinergic neuroreceptors (ORXR), and sympatho-inhibitory neuropeptide catestatin (CST) are widely involved with ischemic episodes. In this study, it was possible to induce in vitro ischemic conditions of the hamster (Mesocricetus auratus) hippocampal and hypothalamic neuronal cultures, grown on a newly compartmentalized membrane system, via oxygen and glucose deprivation (OGD). These cultures displayed notably differentiated NMDARergic and ORXergic receptor expression activities along with evident brain-derived neurotrophic factor (BDNF) plus orexin A (ORX-A) secretion, especially under co-cultured conditions. Interestingly, addition of CST in OGD-insulted hippocampal cells accounted for upregulated GluN1 and ORX1R transcripts that in the case of the latter neuroreceptor was very strongly (p < 0.001) increased when co-cultured with hypothalamic cells. Similarly, hypothalamic neurons supplied very evident upregulations of GluN1, ORX1R, and above all of GluN2A transcripts along with increased BDNF and ORX-A secretion in the presence of hippocampal cells. Overall, the preferential CST effects on BDNF plus ORX-A production together with altered NMDAR and ORXR levels, especially in co-cultured hypothalamic cells pointed to ORX-containing neurons as major protective constituents against ischemic damages thus opening new scenarios on the cross-talking roles of CST during ischemic disorders.

Distinct α subunit variations of the hypothalamic GABAA receptor triplets (αßγ) are linked to hibernating state in hamsters.

BACKGROUND: The structural arrangement of the γ-aminobutyric acid type A receptor (GABAAR) is known to be crucial for the maintenance of cerebral-dependent homeostatic mechanisms during the promotion of highly adaptive neurophysiological events of the permissive hibernating rodent, i.e the Syrian golden hamster. In this study, in vitro quantitative autoradiography and in situ hybridization were assessed in major hypothalamic nuclei. Reverse Transcription Reaction-Polymerase chain reaction (RT-PCR) tests were performed for specific GABAAR receptor subunit gene primers synthases of non-hibernating (NHIB) and hibernating (HIB) hamsters. Attempts were made to identify the type of αßγ subunit combinations operating during the switching ON/OFF of neuronal activities in some hypothalamic nuclei of hibernators. RESULTS: Both autoradiography and molecular analysis supplied distinct expression patterns of all α subunits considered as shown by a strong (p < 0.01) prevalence of α1 ratio (over total α subunits considered in the present study) in the medial preoptic area (MPOA) and arcuate nucleus (Arc) of NHIBs with respect to HIBs. At the same time α2 subunit levels proved to be typical of periventricular nucleus (Pe) and Arc of HIB, while strong α4 expression levels were detected during awakening state in the key circadian hypothalamic station, i.e. the suprachiasmatic nucleus (Sch; 60%). Regarding the other two subunits (ß and γ), elevated ß3 and γ3 mRNAs levels mostly characterized MPOA of HIBs, while prevalently elevated expression concentrations of the same subunits were also typical of Sch, even though this time during the awakening state. In the case of Arc, notably elevated levels were obtained for ß3 and γ2 during hibernating conditions. CONCLUSION: We conclude that different αßγ subunits are operating as major elements either at the onset of torpor or during induction of the arousal state in the Syrian golden hamster. The identification of a brain regional distribution pattern of distinct GABAAR subunit combinations may prove to be very useful for highlighting GABAergic mechanisms functioning at least during the different physiological states of hibernators and this may have interesting therapeutic bearings on neurological sleeping disorders.

A sexually dimorphic distribution pattern of the novel estrogen receptor G-protein-coupled receptor 30 in some brain areas of the hamster.

The isolation of the G-protein-coupled receptor 30 (GPR30), an orphan membrane receptor unrelated to nuclear estrogen receptors (ERs), has become a key factor towards the unraveling of rapid estrogen action. This membrane receptor together with cellular signaling intermediaries, i.e., extracellular signal-dependent kinases 1 and 2, may promote neuronal proliferation and differentiation activities. In the present study, an evident gene expression pattern of GPR30 characterized postnatal 7 (young) and 60 (adult) days of age hamsters as shown by its heterogeneous mRNA distribution in hypothalamic, amygdalar and cerebellar areas of both sexes. In particular, most of the brain areas considered in the adult hamster plus only the amygdala and cerebellum of young animals behaved in a sexually dimorphic fashion. This similar pattern was also detected for the ERalpha and beta, as shown by the latter receptor prevailing in young and adult females, while the former predominated in young females. Even for the two kinases, a sexually dimorphic distribution was featured above all for young hamsters. Overall, the findings of the present study established a distinct expression pattern of the novel ER (GPR30) that may operate differently in some brain areas of the hamster and this may provide interesting insights regarding its probable neuroprotective role during the execution of some hibernating states, which are typical of our rodent model.

Neuroactive steroid mechanisms and GABA type A receptor subunit assembly in hypothalamic and extrahypothalamic regions.

Gonadal- and neuronal-derived steroids are capable of altering brain functions through two basic mechanisms: slow (genomic) and rapid (novel nongenomic membrane) types of activities. The genomic activities that are circumscribed to the numerous neuronal and glial expressed receptor actions involve transcriptional processes regulated largely by classical steroids. On the other hand, rapid nongenomic activities are linked to the stereoselective interactions of potent neuroactive steroids. It appears that both of these steroid mechanisms can be successfully evoked at the ligand-gated heteroligomeric GABA type A receptor. However, the precise structural prerequisites and type of molecular steroid interactions implicated in this neuronal target have not been fully investigated. This article reviews the most common subunits (alpha, beta, and gamma) of the native GABA type A receptor involved in signaling pathways of slow and rapid steroidal mechanisms. Different beta-containing compositions (alpha1beta1-3gamma2) are necessary for the slow type of mechanism, whereas different alpha-containing constructs (alpha2-6beta 1/2 gamma2/2L) are linked to the rapid type. Because of the major role played by neuroactive steroids in GABA-dependent neuroendocrine and sociosexual events, distinction of the specific subunit combination is essential not only for elucidating neuronal communicative expressions during such events but also for elucidating their potential neuroprotective role in neurodegenerative disorders.