Corticotropin Releasing Factor Binding Protein as a Novel Target to Restore Brain Homeostasis: Lessons Learned From Alcohol Use Disorder Research

Stress is well-known to contribute to the development of many psychiatric illnesses including alcohol and substance use disorder (AUD and SUD). The deleterious effects of stress have also been implicated in the acceleration of biological age, and age-related neurodegenerative disease. The physio-pathology of stress is regulated by the corticotropin-releasing factor (CRF) system, the upstream component of the hypothalamic-pituitary-adrenal (HPA) axis. Extensive literature has shown that dysregulation of the CRF neuroendocrine system contributes to escalation of alcohol consumption and, similarly, chronic alcohol consumption contributes to disruption of the stress system. The CRF system also represents the central switchboard for regulating homeostasis, and more recent studies have found that stress and aberrations in the CRF pathway are implicated in accelerated aging and age-related neurodegenerative disease. Corticotropin releasing factor binding protein (CRFBP) is a secreted glycoprotein distributed in peripheral tissues and in specific brain regions. It neutralizes the effects of CRF by sequestering free CRF, but may also possess excitatory function by interacting with CRF receptors. CRFBP’s dual role in influencing CRF bioavailability and CRF receptor signaling has been shown to have a major part in the HPA axis response. Therefore, CRFBP may represent a valuable target to treat stress-related illness, including: development of novel medications to treat AUD and restore homeostasis in the aging brain. This narrative review focuses on molecular mechanisms related to the role of CRFBP in the progression of addictive and psychiatric disorders, biological aging, and age-related neurodegenerative disease. We provide an overview of recent studies investigating modulation of this pathway as a potential therapeutic target for AUD and age-related neurodegenerative disease.

Comparison between Variable and Constant Refrigerant Flow Air Conditioning Systems in Arid Climate: Life Cycle Cost Analysis and Energy Savings

All over the world, there is a call to encourage sustainable energy thinking and implementation. There is an urgent need to consider sustainable solutions in any design projects that are able to reduce energy consumption. In the heating, ventilation, and air conditioning field, the rise of the variable refrigerant flow systems has made big progress. This study presents a life cycle cost analysis to evaluate the economic feasibility of constant refrigerant flow (CRF), and in particular, the conventional ducted unit air conditioning system and the variable refrigerant flow (VRF) system by using detailed cooling load profiles, as well as initial, operating, and maintenance costs. Two operating hours scenarios are utilized and the present worth value technique for life cycle cost analysis is applied to an existing office building located in Qatar, which can be conditioned by CRF and VRF systems. The results indicate that, although the initial cost of the VRF system is higher than that of the CRF system by 23%, the present worth cost of the VRF system is much lower than that of the CRF system at the end of the lifetime due to lower operating costs. There is also a significant energy saving of 27% by using VRF compared to the CRF. The implementation of these results on a national scale will promote the use of sustainable energy technologies such as the VRF system.

Social effects on AVT and CRF systems

Stress and aggression have negative effects on fish welfare and productivity in aquaculture. Thus, research to understand aggression and stress in farmed fish is required. The neuropeptides arginine-vasotocin (AVT) and corticotropin-releasing factor (CRF) are involved in the control of stress and aggression. Therefore, we investigated the effect of agonistic interactions on the gene expression of AVT, CRF and their receptors in juvenile rainbow trout (Oncorhynchus mykiss). The social interactions lead to a clear dominant-subordinate relationship with dominant fish feeding more and being more aggressive. Subordinate fish had an upregulation of the AVT receptor (AVT-R), an upregulation of CRF mRNA levels, and higher plasma cortisol levels. The attenuating effect of AVT on aggression in rainbow trout is proposed to be mediated by AVT-R, and the attenuating effect of the CRF system is proposed to be mediated by CRF.

Amygdalar Corticotropin-Releasing Factor Signaling Is Required for Later-Life Behavioral Dysfunction Following Neonatal Pain

Neonatal pain such as that experienced by infants in the neonatal intensive care unit is known to produce later-life dysfunction including heightened pain sensitivity and anxiety, although the mechanisms remain unclear. Both chronic pain and stress in adult organisms are known to influence the corticotropin-releasing factor (CRF) system in the Central Nucleus of the Amygdala, making this system a likely candidate for changes following neonatal trauma. To examine this, neonatal rats were subjected to daily pain, non-painful handling or left undisturbed for the first week of life. Beginning on postnatal day, 24 male and female rats were subjected to a 4-day fear conditioning and sensory testing protocol. Some subjects received intra-amygdalar administration of either Vehicle, the CRF receptor 1 (CRF1) receptor antagonist Antalarmin, or the CRF receptor 2 (CRF2) receptor antagonist Astressin 2B prior to fear conditioning and somatosensory testing, while others had tissue collected following fear conditioning and CRF expression in the CeA and BLA was assessed using fluorescent in situ hybridization. CRF1 antagonism attenuated fear-induced hypersensitivity in neonatal pain and handled rats, while CRF2 antagonism produced a general antinociception. In addition, neonatal pain and handling produced a lateralized sex-dependent decrease in CRF expression, with males showing a diminished number of CRF-expressing cells in the right CeA and females showing a similar reduction in the number of CRF-expressing cells in the left BLA compared to undisturbed controls. These data show that the amygdalar CRF system is a likely target for alleviating dysfunction produced by early life trauma and that this system continues to play a major role in the lasting effects of such trauma into the juvenile stage of development.

Influences of Farming Practices on Soil Properties and the 2-Acetyl-1-pyrroline Content of Khao Dawk Mali 105 Rice Grains

Khao Dawk Mali 105 (KDML105) is a premium fragrant rice variety and is widely grown in Thung Kula Rong Hai (TKR), northeast Thailand. In the present study, the influence of organic and conventional rice farming (ORF and CRF, respectively) in TKR farmers’ paddy fields on soil properties and their relationship with 2-acetyl-1-pyrroline (2AP) in KDML105 rice grains were investigated. The results indicated that the ORF system had a strong positive effect on major soil quality indicators and the 2AP content in the rice grains. The soil organic matter (SOM) was approximately twice as much in the ORF than in the CRF system, thus leading to much higher total nitrogen (TN), humic acid (HA), and microbial populations in the ORF system. The higher SOM in the ORF system not only enhanced the soil quality indicators but also contributed to approximately 3.5 times higher 2AP than in the CRF system. Principle component analysis indicated a close correlation among SOM, TN, HA, and microbial population under the ORF system; these variables exhibited strong correlations with the 2AP contents in KDML105 rice grains.