Keratin 5 in Lung Cancer Specimens: Comparison of Four Antibody Clones and KRT5 mRNA-ISH.

Recent improvements in the medical treatment of non-small cell lung carcinoma have made the histopathological distinction between adenocarcinomas (ACs) and squamous cell carcinomas (SCCs) increasingly important. One immunohistochemical marker of squamous differentiation is Keratin 5 (K5). Several K5 antibody clones are commercially available, and data from external quality assessment (NordiQC) have shown large variations in their performance. However, comparing antibody performance characteristics of optimized K5 immunohistochemical assays in lung cancer specimens is needed. Tissue microarrays comprising 31 SCCs, 59 ACs, 17 large cell carcinomas, 8 large cell neuroendocrine carcinomas, 5 carcinosarcomas, and 10 small cell carcinomas were included. Serial sections from the tissue microarrays were stained using optimized assays based on the K5 mouse monoclonal antibodies D5/16 B4 and XM26, and the K5 rabbit monoclonal antibodies SP27 and EP1601Y, respectively. The staining reactions were assessed using H-score (0-300). In addition, p40 immunohistochemistry and KRT5 mRNA-ISH analyses were conducted. Clone SP27 showed significantly higher analytical sensitivity than the other 3 clones. However, a distinct positive reaction was observed in 25% of the ACs using clone SP27 but not with the other clones. Clone D5/16 B4 displayed granular staining in 14 ACs, probably representing Mouse Ascites Golgi-reaction. A weak, scattered expression of KRT5 mRNA was seen in 71% of the ACs. In conclusion, the K5 antibody clones D5/16 B4, EP1601Y, and XM26 showed equal sensitivity in lung cancer specimens, but D5/16 B4 also showed nonspecific Mouse Ascites Golgi-reaction. Clone SP27 demonstrated superior analytical sensitivity but lower clinical specificity in the differential diagnosis of SCC versus AC.

Immunohistochemical detection of double-stranded RNA in formalin-fixed paraffin-embedded tissue.

Double-stranded RNA (dsRNA) is produced during most viral infections, and immunohistochemical detection of dsRNA has been proposed as a potential screening marker for viral replication. The anti-dsRNA monoclonal antibody clone 9D5 is more sensitive than the established clone J2 but has not been validated in formalin-fixed paraffin-embedded (FFPE) tissue. This study aimed to test and compare the performance of the anti-dsRNA monoclonal antibodies, 9D5 and J2, in FFPE tissue using an automated staining platform. Archived clinical tissue samples with viral infections (n = 34) and uninfected controls (n = 30) were examined. Immunohistochemical staining for dsRNA (9D5 and J2) and virus-specific epitopes was performed. 9D5 provided a similar staining pattern but a higher signal-to-noise ratio than J2. The following proportions of virus-infected tissue samples were dsRNA-positive: SARS-CoV-2 (5/5), HPV (6/6), MCV (5/5), CMV (5/6), HSV (4/6), and EBV (0/6). Also, 18 of 30 uninfected samples were dsRNA positive, and an association between fixation time and intensity was observed. However, signals in all samples were markedly reduced by pretreatment with dsRNA-specific RNAse-III, indicating a specific reaction. In conclusion, dsRNA can be demonstrated in most viral infections with immunohistochemistry in FFPE tissue but with low clinical specificity. The antibody clone 9D5 performs better than clone J2.

Estrogen modulates metabolic risk profile after resistance training in early postmenopausal women: a randomized controlled trial.

OBJECTIVE: Women experience an unhealthy change in metabolic risk profile at menopause. The purpose of the present study was to determine effects of resistance training with or without transdermal estrogen therapy (ET) on adipose tissue mass and metabolic risk profile in early postmenopausal women. METHODS: A double-blinded randomized controlled trial, where healthy, untrained postmenopausal women were allocated to supervised resistance training with placebo (PLC, n = 16) or transdermal ET (n = 15) for 12 weeks. Endpoints with prespecified hypotheses were the change in total fat mass (FM) (main endpoint) and the change in visceral FM (secondary endpoint) from before to after the intervention. Additionally, prespecified endpoints of body composition, metabolic health-related blood markers, fat%, fat cell size, and lipogenic markers in subcutaneous adipose tissue (SAT) from abdominal and femoral region were explored. RESULTS: Compared with the ET group, the PLC group experienced a greater reduction (time × treatment interaction P < 0.05) in total FM (PLC vs ET: -5.6% vs -1.1%) and visceral FM (-18.6% vs -6.8%), and femoral SAT (-5.6% vs 1.0%), but not abdominal SAT mass (-8.5% vs -2.8%, P = 0.15).The ET group improved their metabolic blood profile by reduced low-density lipoprotein, glucose and hemoglobin A1c compared with PLC (time × treatment interaction P < 0.05). The intervention induced changes in lipolytic markers of abdominal SAT, whereas no changes were detected in femoral SAT. CONCLUSION: Use of transdermal ET reduced adipose tissue loss, but improved metabolic blood markers when combined with 12 weeks of progressive resistance training in early postmenopausal women.

Synthesis and Characterization of the Novel Rodent-Active and CNS-Penetrant P2X7 Receptor Antagonist Lu AF27139.

There remains an insufficient number of P2X7 receptor antagonists with adequate rodent potency, CNS permeability, and pharmacokinetic properties from which to evaluate CNS disease hypotheses preclinically. Herein, we describe the molecular pharmacology, safety, pharmacokinetics, and functional CNS target engagement of Lu AF27139, a novel rodent-active and CNS-penetrant P2X7 receptor antagonist. Lu AF27139 is highly selective and potent against rat, mouse, and human forms of the receptors. The rat pharmacokinetic profile is favorable with high oral bioavailability, modest clearance (0.79 L/(h kg)), and good CNS permeability. In vivo mouse CNS microdialysis studies of lipopolysaccharide (LPS)-primed and 2'(3')-O-(benzoylbenzoyl)adenosine-5'-triphosphate (BzATP)-induced IL-1ß release demonstrate functional CNS target engagement. Importantly, Lu AF27139 was without effect in standard in vitro and in vivo toxicity studies. Based on these properties, we believe Lu AF27139 will be a valuable tool for probing the role of the P2X7 receptor in rodent models of CNS diseases.

NordiQC Assessments of Keratin 5 Immunoassays.

This paper is number 7 in a series developed through a partnership between ISIMM and NordiQC with the purpose of reporting research assessing the performance characteristics of immunoassays in an external proficiency testing program.

Estrogen Receptor-α Quantification in Breast Cancer: Concordance Between Immunohistochemical Assays and mRNA-In Situ Hybridization for ESR1 Gene.

Immunohistochemical (IHC) quantification of estrogen receptor-α (ER) is used for assessment of treatment regimen in breast cancer. Different ER IHC assays may produce diverging results, because of different antibody clones, protocols, and stainer platforms. Objective tissue-based techniques to assess sensitivity and specificity of IHC assays are therefore needed. We tested the usability of ER mRNA-in situ hybridization (mRNA-ISH) in comparison with assays based on clones SP1 and 6F11. We selected 56 archival specimens according to their reported ER IHC positivity, representing a wide spectrum from negative to strongly positive cases. The specimens were used to prepare 4 TMAs with 112 cores. Serial sections of each TMA were stained for ER and pan-cytokeratin (PCK) by IHC and ESR1 (ER gene) by mRNA-ISH. Digital image analysis (DIA) was used to determine ER IHC H-score. ESR1 mRNA-ISH was scored both manually and by DIA. DIA showed a nonlinear correlation between IHC and ESR1 mRNA-ISH with R-values of 0.80 and 0.78 for the ER antibody clones SP1 and 6F11, respectively. Comparison of manual mRNA-ISH scoring categories and SP1 and 6F11 IHC H-scores showed a highly significant relationship (P<0.001). In conclusion, the study showed good correlation between mRNA-ISH and IHC, suggesting that mRNA-ISH can be a valuable tool in the assessment of the sensitivity and specificity of ER IHC assays.

Communication is key: the utility of a revised neuropsychological report format.

OBJECTIVE: The neuropsychological report is a critical tool for communicating evaluation results to multiple audiences who have varying knowledge about neuropsychology and often have limited ability to review long, complex reports. Considerable time is spent writing these reports and challenges persist related to readability, length/complexity, and billable clinical time (which may be capped by third-party payors or families' ability to pay). METHODS: This quality improvement effort systematically evaluated the redesign of pediatric neuropsychological reports in an outpatient clinic serving primarily medical populations. RESULTS: Revised reports were shorter, with improved readability, structure, and effectiveness in communicating results and recommendations. Improved clinical efficiency was also observed. CONCLUSIONS: We suggest that adaptation to efficient, readable, and effective reports is possible within the practice of neuropsychology. Findings encourage replication in other settings. Through collaboration with key stakeholders, providers can identify their populations' and audience's unique needs and set report targets accordingly. To encourage that practice, we summarize our general process, provide a set of guidelines that can be adapted across multiple settings, and include an appended sample report.

From isolated diamondoids to a van-der-Waals crystal: A theoretical and experimental analysis of a trishomocubane and a diamantane dimer in the gas and solid phase.

The electronic properties of sp2/sp3 diamondoids in the crystalline state and in the gas phase are presented. Apparent differences in electronic properties experimentally observed by resonance Raman spectroscopy in the crystalline/gas phase and absorption measurements in the gas phase were investigated by density functional theory computations. Due to a reorganization of the molecular orbitals in the crystalline phase, the HOMO (highest occupied molecular orbital) and LUMO (lowest unoccupied molecular orbital) energy gaps are lowered significantly by 0.5 eV-1 eV. The π → π* transition is responsible for large absorption in both gas and crystalline phases. It further causes a large increase in the Raman intensity of the C=C stretch vibration when excited resonantly. By resonance Raman spectroscopy we were able to determine the C=C bond length of the trishomocubane dimer to exhibit 1.33 Å in the ground and 1.41 Å in the excited state.

Asc-1 Transporter Regulation of Synaptic Activity via the Tonic Release of d-Serine in the Forebrain.

d-Serine is a co-agonist of NMDA receptors (NMDARs) whose activity is potentially regulated by Asc-1 (SLC7A10), a transporter that displays high affinity for d-serine and glycine. Asc-1 operates as a facilitative transporter and as an antiporter, though the preferred direction of d-serine transport is uncertain. We developed a selective Asc-1 blocker, Lu AE00527, that blocks d-serine release mediated by all the transport modes of Asc-1 in primary cultures and neocortical slices. Furthermore, d-serine release is reduced in slices from Asc-1 knockout (KO) mice, indicating that d-serine efflux is the preferred direction of Asc-1. The selectivity of Lu AE00527 is assured by the lack of effect on slices from Asc-1-KO mice, and the lack of interaction with the co-agonist site of NMDARs. Moreover, in vivo injection of Lu AE00527 in P-glycoprotein-deficient mice recapitulates a hyperekplexia-like phenotype similar to that in Asc-1-KO mice. In slices, Lu AE00527 decreases the long-term potentiation at the Schaffer collateral-CA1 synapses, but does not affect the long-term depression. Lu AE00527 blocks NMDAR synaptic potentials when typical Asc-1 extracellular substrates are present, but it does not affect AMPAR transmission. Our data demonstrate that Asc-1 mediates tonic co-agonist release, which is required for optimal NMDAR activation and synaptic plasticity.

Selegiline induces a wake promoting effect in rats which is related to formation of its active metabolites.

The goal of the present work was to characterise the effects of selegiline on the rat sleep pattern. Furthermore, for comparative purposes, the pharmacokinetics of selegiline and its metabolites in brain and plasma were investigated, and microdialysis experiments were performed to examine the resulting effect on dopamine, noradrenaline and serotonin levels. Selegiline (1, 5, 10 and 30mg/kg) was found to dose-dependently increase the time spent awake following acute dosing. The pharmacokinetic assessment of selegiline showed that, following an oral dose of 5mg/kg, low circulating levels of the parent compound were found relative to those of biotransformed l-methamphetamine and l-amphetamine. The time course of selegiline-induced wakefulness was shown to follow the time course of l-methamphetamine and l-amphetamine in brain, suggesting that these metabolites are responsible for the modulation of sleep architecture. Furthermore, selegiline (5mg/kg) caused a significant increase of extracellular levels of DA (250%) and NA (200%), but not of 5-HT, in the rat prefrontal cortex. In summary, an integrated experimental approach was undertaken here to evaluate selegiline's effect on sleep architecture in rats in relation to its pharmacokinetics and changes in monoaminergic neurotransmitter levels in the brain. The effect of selegiline on sleep was likely mediated by an increase of dopamine and noradrenaline levels in the brain caused by the formed metabolites.

Lung perfusion and emphysema distribution affect the outcome of endobronchial valve therapy.

The exclusion of collateral ventilation (CV) and other factors affect the clinical success of endoscopic lung volume reduction (ELVR). However, despite its benefits, the outcome of ELVR remains difficult to predict. We investigated whether clinical success could be predicted by emphysema distribution assessed by computed tomography scan and baseline perfusion assessed by perfusion scintigraphy. Data from 57 patients with no CV in the target lobe (TL) were retrospectively analyzed after ELVR with valves. Pulmonary function tests (PFT), St George's Respiratory Questionnaire (SGRQ), and 6-minute walk tests (6MWT) were performed on patients at baseline. The sample was grouped into high and low levels at the median of TL perfusion, ipsilateral nontarget lobe (INL) perfusion, and heterogeneity index (HI). These groups were analyzed for association with changes in outcome parameters from baseline to 3 months follow-up. Compared to baseline, patients showed significant improvements in PFT, SGRQ, and 6MWT (all P≤0.001). TL perfusion was not associated with changes in the outcome. High INL perfusion was significantly associated with increases in 6MWT (P=0.014), and high HI was associated with increases in forced expiratory volume in 1 second (FEV1), (P=0.012). Likewise, there were significant correlations for INL perfusion and improvement of 6MWT (r=0.35, P=0.03) and for HI and improvement in FEV1 (r=0.45, P=0.001). This study reveals new attributes that associate with positive outcomes for patient selection prior to ELVR. Patients with high perfusions in INL demonstrated greater improvements in 6MWT, while patients with high HI were more likely to respond in FEV1.

Endoscopic treatment of colorectal perforations--a systematic review.

INTRODUCTION: Iatrogenic colon perforation is a feared complication to colonoscopy. Optimal management of the complication remains controversial. Traditionally, patients have been referred to surgery. Now, with technological advances, endoscopic closure is increasingly performed as minimally invasive therapy. The aim of this systematic review was to assess the existing evidence in this field. METHODS: Literature was searched on PubMed, Embase and the Cochrane databases. Papers found were reported according to the PRISMA guidelines. Trials on animals were excluded. RESULTS: A total of 32 articles were assessed, including 19 case reports, one case control, three prospective studies and nine retrospective studies. The total number of patients who have undergone endoscopic closure (apart from case reports) and reported in the literature is 203 patients. Studies have reported a clinical success rate of 87.8% (standard deviation: ± 13.0%) on average and a median of 92.3% (range: 58.6-100%). The total number of patients needing surgery after attempted clip closure was 30 (14.7%); another four were found to have sealed perforations during surgery. One patient died after clip failure (0.5%). Articles presented a favourable, high outcome for endoscopic closure of iatrogenic colorectal perforations. CONCLUSION: In a highly selective group of patients, endoscopic closure of iatrogenic colon perforations is recommended if the expertise is available.

New 4-Functionalized Glutamate Analogues Are Selective Agonists at Metabotropic Glutamate Receptor Subtype 2 or Selective Agonists at Metabotropic Glutamate Receptor Group III.

The metabotropic glutamate (Glu) receptors (mGluRs) play key roles in modulating excitatory neurotransmission in the brain. In all, eight subtypes have been identified and divided into three groups, group I (mGlu1,5), group II (mGlu2,3), and group III (mGlu4,6-8). In this article, we present a L-2,4-syn-substituted Glu analogue, 1d, which displays selective agonist activity at mGlu2 over the remaining mGluR subtypes. A modeling study and redesign of the core scaffold led to the stereoselective synthesis of four new conformationally restricted Glu analogues, 2a-d. Most interestingly, 2a retained a selective agonist activity profile at mGlu2 (EC50 in the micromolar range), whereas 2c/2d were both selective agonists at group III, subtypes mGlu4,6,8. In general, 2d was 20-fold more potent than 2c and potently activated mGlu4,6,8 in the low-mid nanomolar range.

Outcomes of Endobronchial Valve Treatment Based on the Precise Criteria of an Endobronchial Catheter for Detection of Collateral Ventilation under Spontaneous Breathing.

BACKGROUND: Endoscopic lung volume reduction with valves is a valid therapeutic option for COPD patients with severe emphysema. The exclusion of interlobar collateral ventilation (CV) is an important predictor of clinical success. OBJECTIVES: Recently, a catheter-based endobronchial in vivo measurement system (Chartis, Pulmonx, USA) has become routine in the clinical evaluation of CV status in target lobes, but the criteria for phenotyping CV by Chartis evaluation have not yet been defined. We asked the questions, how many phenotypes can be identified using Chartis, what are the exact criteria to distinguish them, and how do the Chartis phenotypes respond to valve insertion? METHODS: In a retrospective study, 406 Chartis assessments of 166 patients with severe COPD were analyzed. Four Chartis phenotypes, CV positive (CV+), CV negative (CV-), low flow (LF) and low plateau were identified. Fifty-two patients without CV were treated with valves and followed for 3 months. RESULTS: The Chartis phenotypes were discriminated with respect to decline in expiratory peak flow, increase in resistance index and change in total exhaled volume after 1, 2, 3, 4 and 5 min of measurement time (p < 0.0001, ANOVA), and the cutoff criteria were defined accordingly. To examine the application of these phenotyping criteria, students applied them to 100 Chartis assessments, and they demonstrated almost perfect inter- and intraobserver agreements (x03BA; > 0.9). Compared to baseline, CV- and LF patients with ipsilateral CV- lobe showed an improvement in FEV1 (p < 0.05), vital capacity (p < 0.05) and target lobe volume reduction (p < 0.005) after valve insertion. CONCLUSION: This study describes the most prevalent Chartis phenotypes.

Persistent astrocyte activation in the fragile X mouse cerebellum.

BACKGROUND: Fragile X Syndrome, the most common single gene cause of autism, results from loss of the RNA-binding protein FMRP. Although FMRP is highly expressed in neurons, it has also recently been identified in glia. It has been postulated that in the absence of FMRP, abnormal function of non-neuronal cells may contribute to the pathogenesis of the disorder. We previously demonstrated reduced numbers of oligodendrocyte precursor cells and delayed myelination in the cerebellum of fragile X (Fmr1) knockout mice. METHODS: We used quantitative western blotting and immunocytochemistry to examine the status of astrocytes and microglia in the cerebellum of Fmr1 mice during development and in adulthood. RESULTS: We report increased expression of the astrocyte marker GFAP in the cerebellum of Fmr1 mice starting in the second postnatal week and persisting in to adulthood. At 2 weeks postnatal, expression of Tumor Necrosis Factor Receptor 2 (TNFR2) and Leukemia Inhibitory Factor (LIF) were elevated in the Fmr1 KO cerebellum. In adults, expression of TNFR2 and the glial marker S100ß were also elevated in Fmr1 knockouts, but LIF expression was not different from wild-type mice. We found no evidence of microglial activation or neuroinflammation at any age examined. CONCLUSIONS: These findings demonstrate an atypical pattern of astrogliosis in the absence of microglial activation in Fmr1 knockout mouse cerebellum. Enhanced TNFR2 and LIF expression in young mice suggests that changes in the expression of astrocytic proteins may be an attempt to compensate for delayed myelination in the developing cerebellum of Fmr1 mice.

Rectal Hodgkin lymphoma in a patient with ulcerative colitis: a case study.

A case of Hodgkin lymphoma located in the rectum of a patient with ulcerative colitis is described. The patient was a 44 year old male treated with thiopurines for ulcerative colitis for ten years. He was admitted with malaise, weight loss and abdominal pain. Endoscopy revealed a large ulcerative lesion involving the rectum and distal part of the sigmoid colon. Although it macroscopically resembled a rectal cancer, repeated biopsies did not reveal any malignancy. In order to resolve the symptoms of stenosis and to get the final diagnosis a recto-sigmoid resection was performed. Pathologic examination revealed nodular sclerosis classical Hodgkin lymphoma, positive for Epstein Barr Virus. Subsequent examination revealed disseminated disease involving the pelvic wall, liver, and bone marrow. The patient is currently receiving chemotherapeutic treatment, and follow-up shows disease remission.Hodgkin lymphoma associated with immunosuppressive therapy is rare. However, patients with ulcerative colitis receiving such treatment are at increased risk of lymphoproliferative disordes, potentially due to loss of immunosurveillance and presence of oncogenic viruses (i.e. Epstein-Barr virus). Virtual Slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/6156776351558952.

UV resonance Raman analysis of trishomocubane and diamondoid dimers.

We present resonance Raman measurements of crystalline trishomocubane and diamantane dimers containing a C=C double bond. Raman spectra were recorded with excitation energies between 2.33 eV and 5.42 eV. The strongest enhancement is observed for the C=C stretch vibration and a bending mode involving the two carbon atoms of the C=C bond, corresponding to the B2g wagging mode of ethylene. This is associated with the localization of the π-HOMO and LUMO and the elongation of the C=C bond length and a pyramidalization of the two sp(2)-hybridized carbon atoms at the optical excitation. The observed Raman resonance energies of the trishomocubane and diamantane dimers are significantly lower than the HOMO-LUMO gaps of the corresponding unmodified diamondoids.

Delayed myelination in a mouse model of fragile X syndrome.

Fragile X Syndrome is the most common inherited cause of autism. Fragile X mental retardation protein (FMRP), which is absent in fragile X, is an mRNA binding protein that regulates the translation of hundreds of different mRNA transcripts. In the adult brain, FMRP is expressed primarily in the neurons; however, it is also expressed in developing glial cells, where its function is not well understood. Here, we show that fragile X (Fmr1) knockout mice display abnormalities in the myelination of cerebellar axons as early as the first postnatal week, corresponding roughly to the equivalent time in human brain development when symptoms of the syndrome first become apparent (1-3 years of age). At postnatal day (PND) 7, diffusion tensor magnetic resonance imaging showed reduced volume of the Fmr1 cerebellum compared with wild-type mice, concomitant with an 80-85% reduction in the expression of myelin basic protein, fewer myelinated axons and reduced thickness of myelin sheaths, as measured by electron microscopy. Both the expression of the proteoglycan NG2 and the number of PDGFRα+/NG2+ oligodendrocyte precursor cells were reduced in the Fmr1 cerebellum at PND 7. Although myelin proteins were still depressed at PND 15, they regained wild-type levels by PND 30. These findings suggest that impaired maturation or function of oligodendrocyte precursor cells induces delayed myelination in the Fmr1 mouse brain. Our results bolster an emerging recognition that white matter abnormalities in early postnatal brain development represent an underlying neurological deficit in Fragile X syndrome.

Biomechanical evaluation of macro and micro designed screw-type implants: an insertion torque and removal torque study in rabbits.

OBJECTIVE: To investigate the combined effect of macro and pitch shortened threads on primary and secondary stability during healing, but before dynamic loading. MATERIALS AND METHODS: Two sets of turned implants with different macro geometry were prepared. The test group possessed pitch shortened threads in between the large threads and the control group did not have thread alterations. The two implant groups were placed in both femur and tibiae of 10 lop-eared rabbits, and at the time of implant insertion, insertion torques were recorded. After 4 weeks, all implants were subjected to removal torque tests. RESULTS: The insertion torque values for the control and test groups for the tibia were 15.7 and 20.6 Ncm, respectively, and for the femur, 11.8, and 12.8 Ncm respectively. The removal torque values for the control and test groups in the tibia were 7.9 and 9.1 Ncm, respectively, and for the femur, 7.9 and 7.7 Ncm respectively. There was no statistically significant difference between the control and test groups. CONCLUSION: Under limited dynamic load, the addition of pitch shortened threads did not significantly improve either the primary or the secondary stability of the implants in bone.

The role of the innate immune system in psychiatric disorders.

There is by now substantial clinical evidence for an association between specific mood disorders and altered immune function. More recently, a number of hypotheses have been forwarded to explain how components of the innate immune system can regulate brain function at the cellular and systems levels and how these may underlie the pathology of disorders such as depression, PTSD and bipolar disorder. In this review we draw reference to biochemical, cellular and animal disease models, as well as clinical observations to elucidate the role of the innate immune system in psychiatric disorders. Proinflammatory cytokines, such as IL-1ß IL-6 and TNFα, which feature prominently in the immune response to pathogen in the periphery, have unique and specific actions on neurons and circuits within the central nervous system. Effects of these signaling molecules on neurotransmission, memory, and glucocorticoid function, as well as animal behaviors such as social withdrawal and fear conditioning relevant to psychiatric disorders are elucidated. Finally, we highlight future directions for studies, including the use of peripheral biomarkers, relevant for developing new therapeutic approaches for treating psychiatric illnesses. This article is part of Special Issue entitled 'neuroinflammation in neurodegeneration and neurodysfunction'.