The impact of limited sucrose intake on perineuronal nets of parvalbumin interneurons in the basolateral amygdala: A potential role in stress resilience.

Natural rewards like regular sucrose consumption can buffer physiological and behavioral stress responses, likely mediated, at least in part, by increased plasticity in parvalbumin-positive (PV+) interneurons in the basolateral amygdala (BLA). As PV+ interneuron plasticity is tightly regulated by specialized extracellular matrix structures called perineuronal nets (PNNs), this study investigated the impact of regular sucrose consumption vs. repetitive stress on the PNNs that surround PV+ interneurons in the BLA, as well as the number of glutamatergic (vGLUT1) and GABAergic (vGAT) appositions that PV+ cells receive.

Developmental functions of microglia: Impact of psychosocial and physiological early life stress.

Microglia play numerous important roles in brain development. From early embryonic stages through adolescence, these immune cells influence neuronal genesis and maturation, guide connectivity, and shape brain circuits. They also interact with other glial cells and structures, influencing the brain's supportive microenvironment.

Inhibition of prefrontal cortex parvalbumin interneurons mitigates behavioral and physiological sequelae of chronic stress in male mice.

Chronic stress leads to hypofunction of the medial prefrontal cortex (mPFC), mechanisms of which remain to be determined. Enhanced activation of GABAergic of parvalbumin (PV) expressing interneurons (INs) is thought to play a role in stress-induced prefrontal inhibition. In this study, we tested whether chemogenetic inhibition of mPFC PV INs after chronic stress can rescue chronic stress-related behavioral and physiological phenotypes.

Molecular neurobiology of loss: a role for basolateral amygdala extracellular matrix.

Psychological loss is a common experience that erodes well-being and negatively impacts quality of life. The molecular underpinnings of loss are poorly understood. Here, we investigate the mechanisms of loss using an environmental enrichment removal (ER) paradigm in male rats.

Differential vulnerability of anterior cingulate cortex cell types to diseases and drugs.

In psychiatric disorders, mismatches between disease states and therapeutic strategies are highly pronounced, largely because of unanswered questions regarding specific vulnerabilities of different cell types and therapeutic responses. Which cellular events (housekeeping or salient) are most affected? Which cell types succumb first to challenges, and which exhibit the strongest response to drugs? Are these events coordinated between cell types? How does disease and drug effect this coordination? To address these questions, we analyzed single-nucleus-RNAseq (sn-RNAseq) data from the human anterior cingulate cortex-a region involved in many psychiatric disorders. Density index, a metric for quantifying similarities and dissimilarities across functional profiles, was employed to identify common or salient functional themes across cell types.

Translationally relevant mouse model of early life cancer and chemotherapy exposure results in brain and small intestine cytokine responses: A potential link to cognitive deficits.

Survivors of acute lymphoblastic leukemia (ALL), the most common childhood cancer, are at increased risk for long-term cognitive problems, including executive function deficits. The chemotherapeutic agent methotrexate (MTX) is used to treat most ALL patients and is closely associated with cognitive deficits. To address how early life cancer chemotherapy leads to cognitive deficits, we developed a translationally relevant mouse model of leukemia survival that exposed mice to leukemic cells and chemotherapeutic drugs (vincristine and MTX, with leucovorin rescue) in early life.

Cellular, molecular, and therapeutic characterization of pilocarpine-induced temporal lobe epilepsy.

Animal models have expanded our understanding of temporal lobe epilepsy (TLE). However, translating these to cell-specific druggable hypotheses is not explored. Herein, we conducted an integrative insilico-analysis of an available transcriptomics dataset obtained from animals with pilocarpine-induced-TLE.

Using protein turnover to expand the applications of transcriptomics.

RNA expression and protein abundance are often at odds when measured in parallel, raising questions about the functional implications of transcriptomics data. Here, we present the concept of persistence, which attempts to address this challenge by combining protein half-life data with RNA expression into a single metric that approximates protein abundance. The longer a protein's half-life, the more influence it can have on its surroundings.

Similarities and dissimilarities between psychiatric cluster disorders.

The common molecular mechanisms underlying psychiatric disorders are not well understood. Prior attempts to assess the pathological mechanisms responsible for psychiatric disorders have been limited by biased selection of comparable disorders, datasets/cohort availability, and challenges with data normalization. Here, using DisGeNET, a gene-disease associations database, we sought to expand such investigations in terms of number and types of diseases.

Brain mechanisms of HPA axis regulation: neurocircuitry and feedback in context Richard Kvetnansky lecture.

Regulation of stress reactivity is a fundamental priority of all organisms. Stress responses are critical for survival, yet can also cause physical and psychological damage. This review provides a synopsis of brain mechanisms designed to control physiological responses to stress, focusing primarily on glucocorticoid secretion via the hypothalamo-pituitary-adrenocortical (HPA) axis.

Differential impact of stress and environmental enrichment on corticolimbic circuits.

Stress exposure can produce profound changes in physiology and behavior that can impair health and well-being. Of note, stress exposure is linked to anxiety disorders and depression in humans. The widespread impact of these disorders warrants investigation into treatments to mitigate the harmful effects of stress.

Sexually diergic hypothalamic-pituitary-adrenal axis responses to selective and non-selective muscarinic antagonists prior to cholinergic stimulation by physostigmine in rats.

Central cholinergic systems regulate the hypothalamic-pituitary-adrenal (HPA) axis differentially in males and females (sexual diergism). We previously investigated the role of muscarinic receptors in this regulation by administering physostigmine (PHYSO), an acetylcholinesterase inhibitor, to male and female rats pretreated with scopolamine (SCOP), a nonselective muscarinic antagonist. SCOP pretreatment enhanced adrenocorticotropic hormone (ACTH) and corticosterone (CORT) responses in both sexes, but males had greater ACTH responses while females had greater CORT responses.