Unraveling the Role of the Blood-Brain Barrier in the Pathophysiology of Depression: Recent Advances and Future Perspectives.

Depression is a highly prevalent psychological disorder characterized by persistent dysphoria, psychomotor retardation, insomnia, anhedonia, suicidal ideation, and a remarkable decrease in overall well-being. Despite the prevalence of accessible antidepressant therapies, many individuals do not achieve substantial improvement. Understanding the multifactorial pathophysiology and the heterogeneous nature of the disorder could lead the way toward better outcomes. Recent findings have elucidated the substantial impact of compromised blood-brain barrier (BBB) integrity on the manifestation of depression. BBB functions as an indispensable defense mechanism, tightly overseeing the transport of molecules from the periphery to preserve the integrity of the brain parenchyma. The dysfunction of the BBB has been implicated in a multitude of neurological disorders, and its disruption and consequent brain alterations could potentially serve as important factors in the pathogenesis and progression of depression. In this review, we extensively examine the pathophysiological relevance of the BBB and delve into the specific modifications of its components that underlie the complexities of depression. A particular focus has been placed on examining the effects of peripheral inflammation on the BBB in depression and elucidating the intricate interactions between the gut, BBB, and brain. Furthermore, this review encompasses significant updates on the assessment of BBB integrity and permeability, providing a comprehensive overview of the topic. Finally, we outline the therapeutic relevance and strategies based on BBB in depression, including COVID-19-associated BBB disruption and neuropsychiatric implications. Understanding the comprehensive pathogenic cascade of depression is crucial for shaping the trajectory of future research endeavors.

Uncovering Sex-Specific Epigenetic Regulatory Mechanism Involving H3k9me2 in Neural Inflammation, Damage, and Recovery in the Internal Carotid Artery Occlusion Mouse Model.

Cerebral ischemic stroke is one of the foremost global causes of death and disability. Due to inadequate knowledge in its sequential disease mechanisms, therapeutic efforts to mitigate acute ischemia-induced brain injury are limited. Recent studies have implicated epigenetic mechanisms, mostly histone lysine acetylation/deacetylation, in ischemia-induced neural damage and death. However, the role of lysine methylation/demethylation, another prevalent epigenetic mechanism in cerebral ischemia has not undergone comprehensive investigation, except a few recent reports, including those from our research cohort. Considering the impact of sex on post-stroke outcomes, we studied both male and female mice to elucidate molecular details using our recently developed Internal Carotid Artery Occlusion (ICAO) model, which induces mild to moderate cerebral ischemia, primarily affecting the striatum and ventral hippocampus. Here, we demonstrate for the first time that female mice exhibit faster recovery than male mice following ICAO, evaluated through neurological deficit score and motor coordination assessment. Furthermore, our investigation unveiled that dysregulated histone lysine demethylases (KDMs), particularly kdm4b/jmjd2b are responsible for the sex-specific variance in the modulation of inflammatory genes. Building upon our prior reportage blocking KDMs by DMOG (Dimethyloxalylglycine) and thus preventing the attenuation in H3k9me2 reduced the post-ICAO transcript levels of the inflammatory molecules and neural damage, our present study delved into investigating the differential role of H3k9me2 in the regulation of pro-inflammatory genes in female vis-à-vis male mice underlying ICAO-induced neural damage and recovery. Overall, our results reveal the important role of epigenetic mark H3k9me2 in mediating sex-specific sequential events in inflammatory response, elicited post-ICAO.

Pharmacogenetics of selective serotonin reuptake inhibitors (SSRI): A serotonin reuptake transporter (SERT)-based approach.

Neuropsychiatric disorders are considered to be the most common cause of disability worldwide. Serotonin and its transporter is a prominent paradigm in mood disorders. Response to selective serotonin reuptake inhibitors (SSRI) is altered due to heterogeneity in the serotonin transporter gene, SLC6A4 (solute carrier family 6 member 4). The reported polymorphisms are found to be in different regions of the transporter gene: promoter region (5-HTTLPR and various single nucleotide polymorphisms within it), intron (STin2), and exon 9 (I425V). The long and short alleles of the 5-HTTLPR gene, which are prevalent among variations, may mediate differential effects. In long allelic variant carriers, an increased response to SSRI and timely recovery is due to increased availability of SERT. Whereas, SERT availability is significantly decreased in short allelic carriers, necessitating a reduction in SSRI dosage due to the increased risk of adverse drug reactions. Thus, pharmacogenetic investigations are required to understand the impact of functional variations on the efficacy and tolerability of SSRI. Identifying the carrier variants may aid in clear-decision making of the treatment regimen, aiding the approach of personalized medication.

Unilateral Cystic Kidney Disease in a Young Female.

Unilateral renal cystic disease has been mostly reported in older male patients; however, this case is novel as the youngest reported case in the literature and in a female patient. We present a 22-year-old female with no past medical history and no family history of renal disease that was incidentally found to have unilateral renal cystic disease on computed tomography imaging. The patient's renal function was not impaired and the cystic kidney was found to be functioning appropriately on an intravenous pyelogram. The unilateral cystic disease is benign but must be differentiated from autosomal dominant polycystic disease to prevent morbidity and mortality.