Genome-Wide Association Study Reveals Novel Candidate Genes Associated with Productivity and Disease Resistance to Moniliophthora spp. in Cacao (Theobroma cacao L.).

Cacao (Theobroma cacao L.), the source of chocolate, is one of the most important commodity products worldwide that helps improve the economic livelihood of farmers. Diseases like frosty pod rot caused by Moniliophthora roreri and witches' broom caused by Moniliophthora perniciosa limit the cacao productivity, this can be solved by using resistant varieties. In the current study, we sequenced 229 cacao accessions using genotyping-by-sequencing to examine the genetic diversity and population structure employing 9,003 and 8,131 single nucleotide polymorphisms recovered by mapping against two cacao genomes (Criollo B97-61/B2 v2 and Matina 1-6 v1.1). In the phenotypic evaluation, three promising accessions for productivity and 10 with good tolerance to the frosty pod rot and witches' broom diseases were found. A genome-wide association study was performed on 102 accessions, discovering two genes associated with productivity and seven to disease resistance. The results enriched the knowledge of the genetic regions associated with important cacao traits that can have significant implications for conservation and breeding strategies like marker-assisted selection.

4'-Chlorodiazepam Protects Mitochondria in T98G Astrocyte Cell Line from Glucose Deprivation.

The translocator protein (TSPO), formerly known as the peripheral-type benzodiazepine receptor (PBR), is considered an important regulator of steroidogenesis and a potential therapeutic target in neurological disorders. Previous evidence suggests that TSPO ligands can protect cells during injury and prevent apoptosis in central nervous system (CNS) cells. However, its actions on astrocytic cells under metabolic injury are not well understood. In this study, we explored whether 4'-chlorodiazepam (Ro5-4864), a TSPO ligand, might protect astrocyte mitochondria under glucose deprivation. Our results showed that 4'-chlorodiazepam preserved cell viability and reduced nuclear fragmentation in glucose-deprived cells. These effects were accompanied by a reduced production of free radicals and maintenance of mitochondrial functions in cells treated with 4'-chlorodiazepam. Finally, our findings suggest that TSPO might be involved in reducing oxidative stress by preserving mitochondrial functions in astrocytic cells exposed to glucose withdrawal.

Protection by Neuroglobin Expression in Brain Pathologies.

Astrocytes play an important role in physiological, metabolic, and structural functions, and when impaired, they can be involved in various pathologies including Alzheimer, focal ischemic stroke, and traumatic brain injury. These disorders involve an imbalance in the blood flow and nutrients such as glucose and lactate, leading to biochemical and molecular changes that cause neuronal damage, which is followed by loss of cognitive and motor functions. Previous studies have shown that astrocytes are more resilient than neurons during brain insults as a consequence of their more effective antioxidant systems, transporters, and enzymes, which made them less susceptible to excitotoxicity. In addition, astrocytes synthesize and release different protective molecules for neurons, including neuroglobin, a member of the globin family of proteins. After brain injury, neuroglobin expression is induced in astrocytes. Since neuroglobin promotes neuronal survival, its increased expression in astrocytes after brain injury may represent an endogenous neuroprotective mechanism. Here, we review the role of neuroglobin in the central nervous system, its relationship with different pathologies, and the role of different factors that regulate its expression in astrocytes.

Tibolone protects astrocytic cells from glucose deprivation through a mechanism involving estrogen receptor beta and the upregulation of neuroglobin expression.

Tibolone, a synthetic steroid used for the prevention of osteoporosis and the treatment of climacteric symptoms in post-menopausal women, may exert tissue selective estrogenic actions acting on estrogen receptors (ERs). We previously showed that tibolone protects human T98G astroglial cells against glucose deprivation (GD). In this study we have explored whether the protective effect of tibolone on these cells is mediated by ERs. Experimental studies showed that both ERα and ERß were involved in the protection by tibolone on GD cells, being ERß preferentially involved on these actions over ERα. Tibolone increased viability of GD cells by a mechanism fully blocked by an ERß antagonist and partially blocked by an ERα antagonist. Furthermore, ERß inhibition prevented the effect of tibolone on nuclear fragmentation, ROS and mitochondrial membrane potential in GD cells. The protective effect of tibolone was mediated by neuroglobin. Tibolone upregulated neuroglobin in T98G cells and primary mouse astrocytes by a mechanism involving ERß and neuroglobin silencing prevented the protective action of tibolone on GD cells. In summary, tibolone protects T98G cells by a mechanism involving ERß and the upregulation of neuroglobin.

Astrocytic modulation of blood brain barrier: perspectives on Parkinson's disease.

The blood-brain barrier (BBB) is a tightly regulated interface in the Central Nervous System (CNS) that regulates the exchange of molecules in and out from the brain thus maintaining the CNS homeostasis. It is mainly composed of endothelial cells (ECs), pericytes and astrocytes that create a neurovascular unit (NVU) with the adjacent neurons. Astrocytes are essential for the formation and maintenance of the BBB by providing secreted factors that lead to the adequate association between the cells of the BBB and the formation of strong tight junctions. Under neurological disorders, such as chronic cerebral ischemia, brain trauma, Epilepsy, Alzheimer and Parkinson's Diseases, a disruption of the BBB takes place, involving a lost in the permeability of the barrier and phenotypical changes in both the ECs and astrocytes. In this aspect, it has been established that the process of reactive gliosis is a common feature of astrocytes during BBB disruption, which has a detrimental effect on the barrier function and a subsequent damage in neuronal survival. In this review we discuss the implications of astrocyte functions in the protection of the BBB, and in the development of Parkinson's disease (PD) and related disorders. Additionally, we highlight the current and future strategies in astrocyte protection aimed at the development of restorative therapies for the BBB in pathological conditions.