European Journal of Neuroscience最新文献

Pain catastrophizing is a prominent psychological factor that is strongly correlated with pain. Although the complex properties of pain catastrophizing vary across different pain phases, the contribution of chronic pain to its progression from a general trait to a higher state remains unclear. This study aimed to examine the neural mechanisms and degree to which pain catastrophizing is reinforced in the context of primary dysmenorrhea (PDM), one of the most prevalent gynaecological complaints experienced by women of reproductive age. Altogether, 29 women with moderate-to-severe PDM were included in this study. Arterial spin labelling was used to quantify the cerebral blood flow (CBF) in each participant in both the pain-free and painful phases. The pain catastrophizing scale (PCS) was completed in two phases, and the Short-Form McGill Pain Questionnaire was completed in the painful phase. Compared with pain catastrophizing in the pain-free phase (PCS_pf), pain catastrophizing in the painful phase (PCS_p) is higher and positively correlated with the composite factor of menstrual pain. CBF analysis indicated that the PCS_p is positively associated with CBF in the frontal cortex, hippocampus and amygdala. The reinforcement of pain catastrophizing correlates with CBF in the prefrontal cortex. Specifically, the medial prefrontal cortex, which correlates with pain state, plays a crucial role in mediating the reinforcing effect of pain in the PCS_p. These results promote the mechanical comprehension of pain catastrophizing management in individuals with chronic pain.

Amnestic mild cognitive impairment (aMCI) is considered as an intermediate stage of Alzheimer's disease, but no MRI biomarkers currently distinguish aMCI from healthy individuals effectively. Fractal dimension, a quantitative parameter, provides superior morphological information compared to conventional cortical thickness methods. Few studies have used cortical fractal dimension values to differentiate aMCI from healthy controls. In this study, we aim to build an automated discriminator for accurately distinguishing aMCI using fractal dimension measures of the cerebral cortex. Thirty aMCI patients and 30 health controls underwent structural MRI of the brain. First, the atrophy of participants' cortical sub-regions of Desikan–Killiany cortical atlas was assessed using fractal dimension and cortical thickness. The fractal dimension is more sensitive than cortical thickness in reducing dimensional effects and may accurately reflect morphological changes of the cortex in aMCI. The aMCI group had significantly lower fractal dimension values in the bilateral temporal lobes, right limbic lobe and right parietal lobe, whereas they showed significantly lower cortical thickness values only in the bilateral temporal lobes. Fractal dimension analysis was able to depict most of the significantly different focal regions detected by cortical thickness, but additionally with more regions. Second, applying the measured fractal dimensions (and cortical thickness) of both cerebral hemispheres, an unsupervised discriminator was built for the aMCI and healthy controls. The proposed fractal dimension-based method achieves 80.54% accuracy in discriminating aMCI from healthy controls. The fractal dimension appears to be a promising biomarker for cortical morphology changes that can discriminate patients with aMCI from healthy controls.

The acoustic startle reflex (ASR) and prepulse inhibition of the ASR (PPI) assess the efficiency of salience processing, a fundamental brain function that is impaired in many psychiatric conditions. Both ASR and PPI depend on noradrenergic transmission, yet the modulatory role of the locus coeruleus (LC) remains controversial. Clonidine (0.05 mg/kg, i.p.), an alpha2-adrenoreceptor agonist, strongly reduced the ASR amplitude. In contrast, chemogenetic LC inhibition only mildly suppressed the ASR and did affect the PPI in virus-transduced rats. The canine adenovirus type 2 (CAV2)–based vector carrying a gene cassette for the expression of inhibitory receptors (hM4Di) and noradrenergic cell–specific promoter (PRSx8) had high cell-type specificity (94.4 ± 3.1%) but resulted in heterogeneous virus transduction of DbH-positive LC neurons (range: 9.2–94.4%). Clozapine-N-oxide (CNO; 1 mg/kg, i.p.), a hM4Di actuator, caused the firing cessation of hM4Di-expressing LC neurons, yet complete inhibition of the entire population of LC neurons was not achieved. Case-based immunohistochemistry revealed that virus injections distal (> 150 μm) to the LC core resulted in partial LC transduction, while proximal (< 50 μm) injections caused neuronal loss due to virus neurotoxicity. Neither the ASR nor PPI differed between the intact and virus-transduced rats. Our results suggest that a residual activity of virus-non-transduced LC neurons might have been sufficient for mediating an unaltered ASR and PPI. Our study highlights the importance of a case-based assessment of the virus efficiency, specificity, and neurotoxicity for targeted cell populations and of considering these factors when interpreting behavioral effects in experiments employing chemogenetic modulation.

Cerebrospinal fluid-contacting neurons (CSF-cNS) are considered mechanoreceptors and chemoreceptors involved in detecting changes in CSF circulation. However, considering that recent data suggest that this type of cell could exert an active response when an external stimulus is sensed, identification of CSF-cNS may be relevant. In this regard, some data suggest that a neuronal connection exists between the ventral region of the hypothalamic paraventricular nucleus (PVN) and rostral agranular insular cortex (RAIC); indeed, a potential CSF-cNS is hypothesized. However, a detailed analysis of this connection has not been conducted. Thus, using neuronal tracers (Fluoro-Gold® (FG) and cholera toxin (ChT)) coupled with transmission electron microscopy and immunofluorescence assays against Fluoro-Gold®, oxytocin (OXT), vasopressin (AVP) and oxytocin receptors (OTR), we describe an oxytocinergic or vasopressinergic CSF-cNS between the PVN and RAIC. Our results showed that CSF-cNS along the PVN labelled with oxytocin and/or AVP were present in dendritic projections near the third ventricle. This CSF-cNS in the PVN seems to project to the RAIC. Inside the RAIC, ultrastructural analysis showed that axons immunopositive for oxytocin from the PVN sustained synaptic connections with neurons that expressed OTR. These findings show that the CSF-cNS from the PVN sends projections to the RAIC. To the best of our knowledge, the relevance of CSF-cNS has not been elucidated; however, we hypothesized that the activation of cells could concomitantly release neuropeptides (i.e., oxytocin and AVP) in the CSF and RAIC. Thus, further analysis of the impact of neuropeptides released into the third ventricle and RAIC is warranted.

Alzheimer's disease (AD) affects the hippocampus during its progression, but the specific observable changes of hippocampal subfields during disease progression remain poorly understood. In this study, we employed an event-based model (EBM) to determine the sequence of occurrence of hippocampal subfield atrophy in mild cognitive impairment (MCI) and AD cohorts. Subjects (207) were included: 86 MCI, 53 AD, and 68 healthy controls from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Participants underwent structural magnetic resonance imaging (MRI) scans to analyse the hippocampal subfields. We assigned each patient to a specific EBM stage, based on the number of their abnormal subfields. A combination of 2-year follow-up MRI scans were applied to demonstrate the longitudinal consistency and utility of the model's staging system. The model estimated that the earliest atrophy occurs in the hippocampal fissure, then spreading to other subregions in both MCI and AD. We identified a marked divergence between the sequences of left and right hippocampal subfields atrophy, so inter-hemispheric asymmetry pattern was further analysed. The sequence of asymmetry index (AI) increases beginning in the molecular and granule cell layers of the dentate gyrus (GC-ML-DG), cornus ammonis (CA) 4, and the molecular layer (ML). Longitudinal analysis confirms the efficacy of the model. In addition, the model stages were significantly correlated with patients' memory scores (p < .05). Collectively, we used a data-driven method to provide new insight into AD hippocampal progression. The present model could aid in understanding of the disease stages, as well as tracking memory decline.

Ilaria, S, Tamara, D, Antonella, J, Elena, M. Role of mitochondria-endoplasmic reticulum contacts in neurodegenerative, neurodevelopmental and neuropsychiatric conditions. The European Journal of Neuroscience 2024; 60(5): 5040–5068. https://doi.org/10.1111/ejn.16485

The author list is incorrectly reported, the authors' first names have been exchanged with their surnames. It should appear as follows:

Serangeli I, Diamanti T, De Jaco A, Miranda E.

And in the extended version as follows:

Ilaria Serangeli, Tamara Diamanti, Antonella De Jaco, Elena Miranda.

We apologise for this error.

Neurodegenerative diseases are characterized by progressive deterioration of the nervous system. Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD) are prominently life-threatening examples of neurodegenerative diseases. The complexity of the pathophysiology in neurodegenerative diseases causes difficulties in diagnosing. Although the drugs temporarily help to correct specific symptoms including memory loss and degeneration, a complete treatment has not been found yet. New therapeutic approaches have been developed to understand and treat the underlying pathogenesis of neurodegenerative diseases. With this purpose, clustered-regularly interspaced short palindromic repeats/CRISPR-associated protein (CRISPR/Cas) technology has recently suggested a new treatment option. Editing of the genome is carried out by insertion and deletion processes on DNA. Safe delivery of the CRISPR/Cas system to the targeted cells without affecting surrounding cells is frequently investigated. Extracellular vesicles (EVs), that is exosomes, have recently been used in CRISPR/Cas studies. In this review, CRISPR/Cas and EV approaches used for diagnosis and/or treatment in AD, PD, ALS, and HD are reviewed. CRISPR/Cas and EV technologies, which stand out as new therapeutic approaches, may offer a definitive treatment option in neurodegenerative diseases.

The biological clock of the suprachiasmatic nucleus (SCN) orchestrates circadian (approximately daily) rhythms of behaviour and physiology that underpin health. SCN cell-autonomous time-keeping revolves around a transcriptional/translational feedback loop (TTFL) within which PERIOD (PER1,2) and CRYPTOCHROME (CRY1,2) proteins heterodimerise and suppress trans-activation of their encoding genes (Per1,2; Cry1,2). To explore its contribution to SCN time-keeping, we used adeno-associated virus–mediated translational switching to express PER2 (tsPER2) in organotypic SCN slices carrying bioluminescent TTFL circadian reporters. Translational switching requires provision of the non-canonical amino acid, alkyne lysine (AlkK), for protein expression. Correspondingly, AlkK, but not vehicle, induced constitutive expression of tsPER2 in SCN neurons and reversibly and dose-dependently suppressed pPer1-driven transcription in PER-deficient (Per1,2-null) SCN, illustrating the potency of PER2 in negative regulation within the TTFL. Constitutive expression of tsPER2, however, failed to initiate circadian oscillations in arrhythmic PER-deficient SCN. In rhythmic, PER-competent SCN, AlkK dose-dependently reduced the amplitude of PER2-reported oscillations as inhibition by tsPER2 progressively damped the TTFL. tsPER2 also dose-dependently lengthened the period of the SCN TTFL and neuronal calcium rhythms. Following wash-out of AlkK to remove tsPER2, the SCN regained TTFL amplitude and period. Furthermore, SCN retained their pre-washout phase: the removal of tsPER2 did not phase-shift the TTFL. Given that constitutive tsCRY1 can regulate TTFL amplitude and period, but also reset TTFL phase and initiate rhythms in CRY-deficient SCN, these results reveal overlapping and distinct properties of PER2 and CRY1 within the SCN, and emphasise the utility of translational switching to explore the functions of circadian proteins.