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At least 19 recordsLinked to original sources
PubMed2025

Contribution of the Brain-Gut-Microbiome Axis to Intergenerational Abnormalities in a Rat Model of Perioperative Neurocognitive Disorder.

BACKGROUND: The brain-gut-microbiome (BGM) axis is a communication network through which the brain and gastrointestinal microbiota interact via neural, hormonal, immune, and gene expression mechanisms. Gut microbiota dysbiosis is thought to contribute to neurocognitive disorders, including perioperative neurocognitive disorder, and to various metabolic abnormalities. Recently, the authors reported that sevoflurane induces neurocognitive deficits in exposed rats as well as their future offspring, with male offspring being particularly affected (intergenerational perioperative neurocognitive disorder). In this study, the authors examined in the same animals whether the intergenerational effects of sevoflurane involve abnormalities in the BGM axis, and whether they are mitigated by paternal pretreatment with either the Na + -K + -Cl - (NKCC1) Cl - transporter inhibitor bumetanide or the glucocorticoid receptor inhibitor RU486, as previously demonstrated for neurocognitive deficits. METHODS: Male Sprague-Dawley rats (F0 generation) were exposed to 2.1% sevoflurane for 3 h on postnatal days 56, 58, and 60 (F0M_S group). Before each sevoflurane exposure, distinct experimental groups of F0 males received bumetanide (F0M_BS group) or RU486 (F0M_RS group). These males were mated on postnatal day 90 to produce offspring (F1 generation). Gut microbiota were profiled using 16S rRNA gene sequencing, and brain changes analyzed via RNA sequencing of hippocampal samples. RESULTS: F1 male offspring of F0M_S sires exhibited heightened corticosterone responses to stress, increased inflammatory markers, altered hippocampal transcriptomes, gut microbiota dysbiosis, elevated serum low-density lipoprotein cholesterol levels, and increased body weight. The only abnormality observed in F1 females was a shift in microbial diversity. F0M_S displayed profound alterations in hippocampal transcriptome, while microbial diversity was the only parameter affected in their gut microbiota. Bumetanide or RU486 mitigated most abnormalities, except increased body weight in F1 males. CONCLUSIONS: Paternal sevoflurane exposure in rats induces BGM axis abnormalities, particularly in male offspring, despite the absence of direct anesthetic exposure. Pretreatment with bumetanide or RU486 showed therapeutic efficacy.

Animals↗
PubMed2026

Microglial modulation in general anesthesia: molecular.

General anesthetics profoundly alter brain function and consciousness, yet the mechanisms underlying these effects remain incompletely understood. Although traditional studies have primarily focused on neuronal targets, accumulating evidence suggests that microglia dynamically respond to anesthetic exposure and may participate in anesthesia-associated neurophysiological changes. Beyond their established immune functions, microglia are increasingly implicated in synaptic remodeling, metabolic regulation, neuronal activity surveillance, and neuron-glia communication. Recent studies indicate that different classes of anesthetic agents modulate microglial activity through diverse and context-dependent mechanisms involving inflammatory signaling, purinergic pathways, calcium dynamics, mitochondrial metabolism, and neural circuit interactions. These responses are associated with postoperative neurocognitive disorders, altered synaptic plasticity, and anesthesia-related changes in brain states. In this review, we summarize current evidence regarding the effects of volatile anesthetics, intravenous anesthetics, and analgesics on microglial function and discuss the molecular, functional, and circuit-level mechanisms underlying anesthesia-associated neuron-microglia interactions. We further highlight the dynamic and heterogeneous nature of microglial responses during anesthesia and discuss current limitations in the field, including the lack of temporally resolved and cell-specific approaches. Understanding these processes may provide insights into anesthesia-associated neurocognitive dysfunction and support the development of neuroimmune-targeted strategies in anesthesiology.

General anesthesia↗
PubMed1976

Serum creatine phosphokinase activity in psychiatrically hospitalized children.

Serum creatine phosphokinase (CPK) activity was determined in a series of 101 sequential admissions to the Pritzker Children's Hospital, an inpatient psychiatric facility. Black children had significantly higher serum CPK levels than whites, and males had significantly higher levels than females, as is the case with adults. There was a higher incidence of CPK elevations in children with organic brain pathology than in children with personality disorders or schizoprenia. Children with chronic symptoms of a psychotic nature did not have increased serum CPK activity, which is similar to the findings in adults. There were no children in the sample with acute psychotic symptoms, so it was not possible to determine whether acute psychosis in children is accompanied by increased serum CPK activity, as it frequently is in psychotics over the age of 17.

Adolescent↗
PubMed1978

Concurrent diagnostic validity of a structured psychiatric interview.

In order to estimate the concurrent validity of a structured psychiatric interview, we compared interview diagnoses obtained for 101 psychiatric inpatients to those recorded in the same patients' hospital charts. For most diagnoses considered, concordance was found to be high. For those in which concordance was low, we examined the reasons for the diagnostic discrepancy. Diagnostic errors that were judged to have occurred on the basis of the structural interview often seemed to have resulted from a lack of longitudinal clinical observation. However, more errors were judged to have occurred in the hospital charts, apparently because of physician oversight. We conclude that the concurrent validity of this structured interview is high and that such examinations might be useful not only for research but also for the routine initial evaluation of psychiatric patients.

Alcoholism↗
PubMed1978

Factors in the rotation of reproduced figures.

Investigated the effectiveness of presenting some of the MPD designs on rotated backgrounds; examination was made of the incidence of a particular rotational error in the records of 246 psychiatric patients. This error, the reproduction of the square of the circle-square design in "square" instead of the correct "diamond" orientation, occurred very much more often when the background was rotated than when it was normal, which confirmed that the orientation of the background had a strong effect on the reproductions. The error was made significantly more often by Ss with brain damage than by those with functional disorders. The findings were discussed in relation to the concept of field-dependence.

Affective Symptoms↗
PubMed1978

Wechsler Memory Scale: a selective review of the literature.

Research on the Wechsler Memory Scale (WMS) is reviewed with respect to questions of its reliability, factor structure, construct validity, and utility. The relationship of Memory Quotient to Full Scale IQ is explored and the conditions under which disparity between the two scores may be clinically useful indicated. Despite its numerous limitations, the WMS has been a sensitive test of short-term verbal memory. As such, it may be helpful in identifying impairment of the dominant (left) temporal lobe and its medial hippocampal connections. The test is badly in need of re-standardization, however, and suggestions for improving the instrument are made.

Adult↗
PubMed1976

[Psychiatry, morphology and behaviour genetics (author's transl)].

No organic substrate is known for endogenous psychoses, neuroses and behaviour disorders. Therefore genetic studies have to depart from the behavioural level. This approach has yielded the empirical risk figures which depend on genetic and environmental factors. Beyond this level behaviour genetics endeavours to clarify the genetic mechanisms underlying normal and abnormal behaviour. In the schizophrenias f.i. several stretegies have been developed to approach the genetic basis: Mathematial models as to the mode of inheritance; use of modified classificatory and diagnostic criteria for genetic analysis; search for phenomena representing steps between genotype and phenotype and showing a clear mode of inheritance, f.i. biochemical or electrophysiological characters. In case the neurotransmitters are not changed in quality or total quantity but in compartmentation in the genetic defect might be localized in the pre- or postsynaptic membranes or receptors. Genetic factors are also involved in nonpsychotic behaviour disorders but to a lesser degree. They can be demonstrated even in psychoses with somatic background.

Catecholamines↗
PubMed1977

Distribution of DSM-II diagnoses in a child psychiatric setting.

While DSM-II contains more diagnostic categories related specifically to children than did the earlier DSM-I, clinical utilization studies of the various categories have not been extensive. The present study reports data on the distribution of diagnoses of childhood disorders and analyzes relationships among several diagnostic categories and subject variables. Results indicate that clinicians are using a wide range of DSM-II diagnoses for childhood disorders, including some which were intended for use with adults as well as those which were designed specifically for children. Transient Situational Disorders and Behavior Disorders are assigned almost equally to two-thirds of the sample. Chi-square analyses revealed a relationship between diagnostic categories and subject variables of age and sex. These data suggest that boys, particularly between the ages of 6 and 13, are more frequently than girls categorized as Behavior Disorder, and that the Transient Situational Disorder category is overutilized for adolescents, both male and female.

Adolescent↗
PubMed1978

Diagnosis and chronic mental illness.

This paper describes the occurrence of chronicity in varying psychiatric illnesses. There is not an unequivocal definition of chronicity, but with the exception of the illnesses that will be described below and that lead directly or indirectly to death from CNS complications of the illness, chronicity will require a duration of a minimum of five years without a significant remission. Chronicity is further differentiated into four different kinds of chronicity: chronic--death, chronic--self-limited, chronic--remission, and chronic--recurrent. The illnesses that may be considered as possibly fulfilling the criteria for chronic will be noted and a method for deciding whether an illness qualifies will be outlined.

Alcoholism↗
PubMed1978

The emergence of the Bowery as a psychiatric dumping ground.

The drastic reduction of State Hospital population in New York over the past decade has led to a demographic relocation of the mentally ill, rather than any real decline in the rate or severity of mental disorders. Unable to function on their own in society and without adequate supportive facilities available, many discharged patients live in the streets and eventually end up on the Bowery, where they are cared for at The Men's Shelter. Studies have shown that over 50% of the current Bowery population has a history of mental illness and that alcoholism is often a secondary, rather than primary diagnosis. The most frequently encountered diagnostic syndromes are mentioned and commented upon. Possible alternative treatment interventions are suggested.

Age Factors↗
PubMed2026

Genetic evidence links hypertension to accelerated brain aging.

Hypertension affects one-third of adults and is a major comorbidity of neurocognitive disorders. The causal relationship, shared genetic architecture, and upstream mechanisms linking hypertension to brain aging remain unclear. Hypertension GWAS datasets from MVP and FinnGen R12 were meta-analyzed as the exposure, and a European-ancestry brain age gap (BAG) GWAS derived from the UK Biobank and LIFE-Adult cohorts was used as the outcome. MR and GSMR assessed causality. LDSC, HDL, and S-LDSC estimated genetic correlation. Four TWAS methods (MAGMA, FUSION, JTI-PrediXcan, FOCUS) mapped associations to genes, followed by SMR for causal validation and PoPS for prioritization. GSMAP with spatial transcriptomics characterized regional and cell-type enrichment. Hypertension and brain aging were genetically correlated, and MR and GSMR analyses suggested a causal effect of hypertension on increased brain age gap. TWAS identified 15 shared Hypertension-BAG genes, 10 supported by SMR. PoPS prioritized TRIM47 as the core gene. Shared signals were enriched in meninges, fiber tracts, cortical layer 1, and CA1 stratum lacunosum/radiatum, with cell-type enrichment in meninges, smooth muscle cells, oligodendrocytes, and astrocyte subtypes. Hypertension is genetically correlated with, and shows evidence of a causal effect on, accelerated brain aging. TRIM47 is a core gene bridging hypertension and BAG. GSMAP-based spatial enrichment provides a hypothesis-generating framework for understanding vascular, meningeal, and myelin-related pathways linking hypertension to increased brain age gap.

Humans↗
PubMed2026

Experimental approaches for investigating sirtuin-mediated mitochondrial function, cellular metabolism, and epigenetic regulation.

Cellular pathways for experimental discovery provide a comprehensive overview of sirtuin biology and its critical involvement in HIV-associated neurocognitive disorders (HAND) and related neurodegenerative diseases, highlighting the translational potential of sirtuin-targeted therapeutic strategies. As NAD+-dependent deacetylases and ADP-ribosyl transferases, sirtuins regulate diverse cellular processes, including stem cell maintenance, cellular proliferation, metabolic homeostasis, apoptosis, autophagy, oxidative stress responses, and genomic stability, all of which contribute to neuronal dysfunction and disease progression. This chapter focuses on key mammalian sirtuins, including SIRT1 and SIRT2, which are primarily localized within the nucleus and cytosol; mitochondrial sirtuins SIRT3, SIRT4, and SIRT5; and nuclear/nucleolar sirtuins SIRT6 and SIRT7. Here, a method with a detailed protocol to isolate compartment-specific sirtuin expression and activity was used: subcellular fractionation was performed using a subcellular fractionation kit to obtain cytosolic and nuclear fractions, while mitochondrial isolation was carried out using Tom20 antibody-conjugated magnetic microbeads. These approaches were applied to brain tissues from HIV-positive individuals, as well as to HIV-Tat-treated human microglial (HMC3) cells and astrocytes. This experimental framework enables accurate assessment of compartment-resolved sirtuin regulation in disease-relevant models. Collectively, the chapter highlights the protective roles of sirtuins in mitigating key pathogenic mechanisms underlying HAND and related neurodegenerative diseases. These findings support the emerging concept that sirtuins represent promising pharmacological targets for the development of novel therapeutic interventions in neurodegeneration and HIV-associated brain disorders.

Humans↗
PubMed2026

In vivo genome editing of central nervous system SIV reservoirs in ART-suppressed rhesus macaques.

Latent human immunodeficiency virus type 1 (HIV-1) reservoirs in the central nervous system (CNS) may sustain viral persistence and neuroinflammation contributing to HIV-associated neurocognitive disorders (HAND) despite suppressive ART. AAV9-delivered CRISPR has successfully edited SIV proviral DNA in peripheral tissues with acceptable safety profiles, but the extent of in vivo genome editing in the brain remains unclear. Using SIV-infected rhesus macaques, we mapped intact proviral DNA across CNS regions and tested systemic AAV9-CRISPR-Cas9 targeting conserved sites within Ψ packaging signal and Gag region. Ten adult rhesus macaques were infected with genetically barcoded SIVmac239, suppressed with ART, then randomized to receive intravenous AAV9-SaCas9 with dual gRNAs (Ψ + Gag) or a Cas9-only control. At necropsy after viral rebound, SIV genomes were detected in multiple brain regions as well as lymphoid tissues, confirming the CNS as a persistent reservoir during ART. Barcode analysis revealed region-specific patterns consistent with compartmentalized CNS persistence. In CRISPR-treated animals, proviral editing was measurable across anatomically distinct CNS sites. These findings demonstrate that intact and potentially replication-competent virus persists in the primate brain under ART and that systemic AAV9-CRISPR can reach and edit proviral DNA in this sanctuary, supporting genome editing as a strategy toward durable remission of CNS reservoirs.

ART↗