Dorsomedial hypothalamus CRF type 1 receptors selectively modulate inhibitory avoidance responses in the elevated T-maze

Silva, Mariana S.; Pereira, Bruno A.; Céspedes, Isabel Cristina; Nascimento, Juliana O.G.; Bittencourt, Jackson C.; Viana, Milena de Barros

doi:10.1016/j.bbr.2014.06.018

Cited by 14 publications

(7 citation statements)

References 53 publications

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“…Transgene was expressed mainly in the ARC and VMH nuclei of the hypothalamus in this study, which might increase the BDNF protein level in the adjacent dorsomedial hypothalamus (DMH). The DMH is a brain area not only involved in physiological functions such as metabolism and environmental threats but is also critically involved in behavioral regulation, particularly fear, anxiety, and panic‐like disorders (Shekhar, Sims, & Bowsher, ; Silva et al, ). Recently, it was reported that loss of corticotropin‐releasing hormone (Crh) in the paraventricular hypothalamus (PVH) results in reduced anxiety behaviors (Zhang et al, ).…”

Section: Discussionmentioning

confidence: 99%

Hypothalamic gene transfer of BDNF promotes healthy aging in mice

et al. 2018

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The aging process and age‐related diseases all involve perturbed energy adaption and impaired ability to cope with adversity. Brain‐derived neurotrophic factor (BDNF) in the hypothalamus plays important role in regulation of energy balance. Our previous studies show that recombinant adeno‐associated virus (AAV)‐mediated hypothalamic BDNF gene transfer alleviates obesity, diabetes, and metabolic syndromes in both diet‐induced and genetic models. Here we examined the efficacy and safety of a built‐in autoregulatory system to control transgene BDNF expression mimicking the body's natural feedback systems in middle‐aged mice. Twelve‐month‐old mice were treated with either autoregulatory BDNF vector or yellow fluorescence protein (YFP) control, maintained on normal diet, and monitored for 28 weeks. BDNF gene transfer prevented the development of aging‐associated metabolic declines characterized by: preventing aging‐associated weight gain, reducing adiposity, reversing the decline of brown fat activity, increasing adiponectin while reducing leptin and insulin in circulation, improving glucose tolerance, increasing energy expenditure, alleviating hepatic steatosis, and suppressing inflammatory genes in the hypothalamus and adipose tissues. Moreover, BDNF treatment reduced anxiety‐like and depression‐like behaviors. These safety and efficacy data provide evidence that hypothalamic BDNF is a target for promoting healthy aging.

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Section: Discussionmentioning

confidence: 99%

Hypothalamic gene transfer of BDNF promotes healthy aging in mice

et al. 2018

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“…It has been previously reported that treatment with antalarmin and antalarmin analogs leads to consistent decreases in anxiety-like behaviors shortly after the drug administration [ 19 , 40 , 41 ]. For these experiments, we tested antalarmin efficacy at a later time point, which would also enable comparisons to the behavioral parameters observed in our prior study using environmental enrichment [ 33 ].…”

Section: Discussionmentioning

confidence: 99%

Antagonizing the corticotropin releasing hormone receptor 1 with antalarmin reduces the progression of endometriosis

et al. 2018

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Endometriosis is a disorder in which endometrial tissue is found outside the uterus causing pain, infertility and stress. Finding effective, non-hormonal and long-term treatments for endometriosis still remains one of the most significant challenges in the field. Corticotropin releasing hormone (CRH) is one of the main signaling peptides within the hypothalamic pituitary adrenal (HPA) axis released in response to stress. CRH can affect nervous and visceral tissues such as the uterus and gut via activation of two types of CRH receptors: CRHR1 and CRHR2. Our aim was to determine if blocking CRHR1 with antalarmin will reduce endometriosis progression. In experiment 1 we induced endometriosis in female rats by suturing uterine horn tissue next to the intestinal mesentery and allowed to progress for 7 days. We determined that after 7 days, there was a significant increase in CRHR1 within endometriotic vesicles as compared to normal uterus. In Experiment 2, we induced endometriosis and administered either antalarmin (20 mg/kg, i.p.) or vehicle during the first 7 days after surgery. A separate group of sham surgery rats served as non-endometriosis controls. Endometriosis was allowed to progress until 60 days after surgery, at which time rats were tested for anxiety behaviors. At the time of sacrifice, endometriotic vesicles, uterus and blood were collected. Treatment with antalarmin significantly reduced the size (67% decrease) and number (30% decrease) of endometriotic vesicles. Antalarmin also prevented the increase in CRH and CRHR1 mRNA within endometriotic vesicles but not of glucocorticoid receptor. Endometriosis did not change anxiety behaviors in the open field and zero-maze tests and prior antalarmin administration did not modify this. Our data provides the first in-vivo demonstration for use of CRHR1 antagonist for the treatment of endometriosis opening the possibility for further exploring CRH signaling as a treatment target for this debilitating disease.

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“…The CRH receptor 1 (CRHR1) triggers the release of the stress response regulating hormone cortisol. Preclinical and clinical studies have indicated that CRHR1 is a possible candidate gene for mood and anxiety disorders[79,125,126]. Weber et al[127] studied different variants located within the CRHR1 gene with regard to possible associations with PD.…”

Section: Resultsmentioning

confidence: 99%

“…CRH plays a central role in the regulation of the HPA axis. Preclinical and clinical studies have indicated that CRHR1 is a possible candidate gene for PD[125,126]. In a multi-level study by Weber et al[127], one allele was found to increase risk for PD in females.…”

Section: Discussionmentioning

confidence: 99%

Functional neuroanatomy in panic disorder: Status quo of the research

Sobanski¹,

Wagner²

2017

WJP

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AIMTo provide an overview of the current research in the functional neuroanatomy of panic disorder.METHODSPanic disorder (PD) is a frequent psychiatric disease. Gorman et al (1989; 2000) proposed a comprehensive neuroanatomical model of PD, which suggested that fear- and anxiety-related responses are mediated by a so-called “fear network” which is centered in the amygdala and includes the hippocampus, thalamus, hypothalamus, periaqueductal gray region, locus coeruleus and other brainstem sites. We performed a systematic search by the electronic database PubMed. Thereby, the main focus was laid on recent neurofunctional, neurostructural, and neurochemical studies (from the period between January 2012 and April 2016). Within this frame, special attention was given to the emerging field of imaging genetics.RESULTSWe noted that many neuroimaging studies have reinforced the role of the “fear network” regions in the pathophysiology of panic disorder. However, recent functional studies suggest abnormal activation mainly in an extended fear network comprising brainstem, anterior and midcingulate cortex (ACC and MCC), insula, and lateral as well as medial parts of the prefrontal cortex. Interestingly, differences in the amygdala activation were not as consistently reported as one would predict from the hypothesis of Gorman et al (2000). Indeed, amygdala hyperactivation seems to strongly depend on stimuli and experimental paradigms, sample heterogeneity and size, as well as on limitations of neuroimaging techniques. Advanced neurochemical studies have substantiated the major role of serotonergic, noradrenergic and glutamatergic neurotransmission in the pathophysiology of PD. However, alterations of GABAergic function in PD are still a matter of debate and also their specificity remains questionable. A promising new research approach is “imaging genetics”. Imaging genetic studies are designed to evaluate the impact of genetic variations (polymorphisms) on cerebral function in regions critical for PD. Most recently, imaging genetic studies have not only confirmed the importance of serotonergic and noradrenergic transmission in the etiology of PD but also indicated the significance of neuropeptide S receptor, CRH receptor, human TransMEMbrane protein (TMEM123D), and amiloride-sensitive cation channel 2 (ACCN2) genes.CONCLUSIONIn light of these findings it is conceivable that in the near future this research will lead to the development of clinically useful tools like predictive biomarkers or novel treatment options.

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Dorsomedial hypothalamus CRF type 1 receptors selectively modulate inhibitory avoidance responses in the elevated T-maze

Cited by 14 publications

References 53 publications

Hypothalamic gene transfer of BDNF promotes healthy aging in mice

Hypothalamic gene transfer of BDNF promotes healthy aging in mice

Antagonizing the corticotropin releasing hormone receptor 1 with antalarmin reduces the progression of endometriosis

Functional neuroanatomy in panic disorder: Status quo of the research

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