Alzheimer’s disease (AD) is the most common form of dementia and is characterized by the excessive deposition of amyloid-β (Aβ) plaques and the formation of neurofibrillary tangles. Numerous new studies also indicate that synaptic damage and loss play crucial roles in AD and form the basis of cognitive impairment. In recent years, synaptic-related proteins have emerged as important biomarkers for the early diagnosis of AD. Among these proteins, neurogranin (Ng), a postsynaptic protein widely present in the dendritic spines of the associative cortex in the brain, plays a significant role in memory, learning, synaptic plasticity, and long-term potentiation (LTP). This review aims to reveal the link between Ng and AD, as well as the potential for the diagnosis of AD, the prediction of the development of the disease, and the identification of a therapeutic target for AD.
Epilepsy, the world’s third most prevalent chronic brain disorder, significantly affects patients’ quality of life and increases the economic burden on families and society. Previous studies have demonstrated that FK506-binding protein 51 (FKBP51) plays a crucial role in synaptic plasticity. However, FKBP51 exhibits different functions under various physiological and pathological conditions. Our study explored the relationship between FKBP51 and epilepsy and its possible mechanism of action. We also analyzed the expression levels of postsynaptic density-95 (PSD95) and synaptophysin (SYP) in the hippocampus to examine the pathophysiology of epilepsy.
A chronic epileptic kindling model was established by injecting pentylenetetrazole (PTZ) intraperitoneally, and a spontaneous seizure model was created by injecting kainic acid (KA) into the dentate gyrus using a stereotaxic apparatus. Endogenous FKBP51 expression was inhibited using adeno-associated virus (AAV)-FKBP51-Small hairpin RNAs (shRNA). The expression of FKBP51, PSD95, and SYP in the hippocampus and synaptosomes was measured through western blotting. Golgi staining and electron microscopy were used to examine spines and synaptic structures.
The results showed a significant increase in FKBP51 expression in the hippocampal tissue of the PTZ- and KA-induced epilepsy model groups. Inhibition of FKBP51 expression through AAV-FKBP51-shRNA resulted in a shorter latency and an elevated seizure grade score in mice. Moreover, the suppression of FKBP51 expression enhanced the expression of synaptic plasticity-related proteins, increased the density of dendritic spines, and elevated the quantity of spherical synaptic vesicles in the presynaptic membrane in the hippocampus.
FKBP51 may serve as an endogenous protective factor in epilepsy by regulating the expression of the synaptic plasticity-related protein PSD95, the density of dendritic spines, and the number of synaptic vesicles in the hippocampal CA1.
Initial manifestations of neurodegenerative ocular conditions, including age-related macular degeneration (AMD) and glaucoma, often remain undetected in the early stages and can begin after the age of 50 years with the likelihood gradually increasing each year thereafter. This study aimed to explore variances in visual and retinal function and anatomy among C57BL/6J mice, aiming to pinpoint differences between biological age and sex factors that potentially lead to the onset of vision impairment.
A longitudinal study evaluated visual acuity (VA) and contrast sensitivity (CS) using optomotor reflex (OMR), and retinal function, encompassing scotopic and photopic measurements, was recorded by electroretinogram (ERG) at 12 months of age. Tissue was subsequently harvested for histological analysis, complementing the in vivo findings. Disparities in visual function were observed between individual male and female mice, necessitating categorization of visual impairment levels to investigate further sex-specific differences in the study’s aging population. Comparisons between sex and the degree of visual impairment were conducted using ANOVA followed by Tukey’s or Bonferroni’s post-hoc corrections and unpaired t-tests. Pearson correlation analysis determined the association between biological factors.
Sex-related disparities were found in the visual function of male (n = 13) and female (n = 18) mice aged 5–12 months. Eyes were categorized by vision impairment: normal vision, or low, moderate, or severe vision loss at the end of the study. Male and female mice differed in mean contrast sensitivity, indicating less sensitivity to fine detail and moving stimuli in female mice (11–12 months old, p < 0.001). Spectral-domain optical coherence tomography (SD-OCT) revealed a thinner retinal outer nuclear layer in male mice (p < 0.0001), although this did not vary across different levels of vision impairment. ERG indicated slower retinal responses in male mice (p < 0.05), while histology showed a significant reduction in the inner plexiform layer thickness in male mice with severe vision loss (p < 0.0001). Conversely, female mice exhibited greater thinning in the photoreceptor layer when vision was unimpaired (p < 0.01).
The study shows that sex and extent of vision impairment influence visual and retinal health, with individual retinal layers differentially changing in thickness over time.
Radiotherapy is one of the primary modalities for oncologic treatment and has been utilized at least once in over half of newly diagnosed cancer patients. Cranial radiotherapy has significantly enhanced the long-term survival rates of patients with brain tumors. However, radiation-induced brain injury, particularly hippocampal neuronal damage along with impairment of neurogenesis, inflammation, and gliosis, adversely affects the quality of life for these patients. Astrocytes, a type of glial cell that are abundant in the brain, play essential roles in maintaining brain homeostasis and function. Despite their importance, the pathophysiological changes in astrocytes induced by radiation have not been thoroughly investigated, and no systematic or comprehensive review addressing the effects of radiation on astrocytes and related diseases has been conducted. In this paper, we review current studies on the neurophysiological roles of astrocytes following radiation exposure. We describe the pathophysiological changes in astrocytes, including astrogliosis, astrosenescence, and the associated cellular and molecular mechanisms. Additionally, we summarize the roles of astrocytes in radiation-induced impairments of neurogenesis and the blood-brain barrier (BBB). Based on current research, we propose that brain astrocytes may serve as potential therapeutic targets for treating radiation-induced brain injury (RIBI) and subsequent neurological and neuropsychiatric disorders.
Identifying the temporal and spectral information in sound is important for understanding speech; indeed, a person who has good spectral resolution usually shows good speech recognition performance. The spectral ripple discrimination (SRD) test is often used to behaviorally determine spectral resolution capacity. However, although the SRD test is useful, it is difficult to apply to populations who cannot execute the behavioral task, such as younger children and people with disabilities. In this study, an objective approach using spectral ripple (SR) stimuli to evoke the acoustic change complex (ACC) response was investigated to determine whether it could objectively evaluate the spectral resolution ability of subjects with normal hearing (NH) and those with hearing loss (HL).
Ten subjects with NH and eight with HL were enrolled in this study. All subjects completed the behavioral SRD test and the objective SR-ACC test. Additionally, the HL subjects completed speech perception performance tests while wearing hearing aids.
In the SRD test, the average thresholds were 6.48 and 1.52 ripples per octave (RPO) for the NH and HL groups, respectively, while in the SR-ACC test, they were 4.90 and 1.35 RPO, respectively. There was a significant difference in the average thresholds between the two groups for the SRD (p < 0.001) and the SR-ACC (p < 0.001) tests. A significant positive correlation was observed between the SRD and SR-ACC tests (ρ = 0.829, p < 0.001). In the HL group, there was a statistically significant relationship between speech recognition performance in noisy conditions and the SR-ACC threshold (ρ = 0.911, p < 0.001 in Sentence score of Korean Speech Audiometry (KSA)).
The results supported the feasibility of the SR-ACC test to objectively evaluate auditory spectral resolution in individuals with HL. This test has potential for use in individuals with HL who are unable to complete the behavioral task associated with the SRD test; therefore, it is proposed as a more inclusive alternative to the SRD test.
This study investigated the characteristics of auditory event-related potentials (AERP) evoked by vowel and consonant contrasts in prelingual deafness adults, who fitted with bilateral hearing aids (HA) in quiet and noisy environments.
Standard stimuli /ba/ (75%) and deviant stimuli (/ga/ and /bu/, 12.5% each) were presented using a passive oddball paradigm in quiet and noisy (+10 decibel [dB] signal-to-noise ratio [SNR]) conditions. Eighteen young adults aged 18–23 years with long-term bilateral HA, and 20 age-matched normal hearing (NH) individuals participated in the study.
The hearing loss (HL) group showed lower N1-P2 and mismatch negativity (MMN) amplitudes and longer N1 and MMN latencies than the NH group. Both groups showed reduced N1-P2 amplitudes and longer MMN latencies in noise. The consonant contrast (/ga/-/ba/) induced lower and delayed MMN than the vowel contrast (/bu/-/ba/).
Young adult bilateral HA users with prelingual severe to profound HL have poorer abilities in processing consonant-vowel syllables than people with NH, especially in noisy conditions and consonant contrast differences. Long-term auditory compensation provided by bilateral HA for people with prelingual severe and profound HL does not seem to enable adequate development of the auditory cortex.
Transcranial magnetic stimulation (TMS) is considered a promising technique to noninvasively modulate cortical excitability and enhance cognitive functions. Despite the growing interest in using TMS to facilitate reading performance in learning disabilities, the immediate TMS-induced effects on brain activity during reading and language tasks in adults with typically developed reading skills remain to be further investigated. In the current study, we explored how a single offline session of intermittent theta burst stimulation (iTBS) delivered to core left-hemisphere nodes of the dorsal and ventral reading network changes brain activity during a spoken and written reading task.
A total of 25 adults with typically developed reading skills participated in a sandwich design TMS-functional magnetic resonance imaging (fMRI) study, which was comprised of a baseline fMRI picture-word identification task that involved matching written or spoken words to picture cues, a single transcranial magnetic stimulation (TMS) session to either the left supramarginal gyrus (SMG) or the left middle temporal gyrus (MTG), followed by a post-stimulation fMRI session. A whole-brain analysis based on the general lineal model (GLM) was used to identify overall activated regions during the processing of spoken and written words. To identify differences between pre-and post-stimulation fMRI sessions, a paired sample t-test was conducted for each group separately (SMG and MTG groups).
Significant differences were found between pre-and post-stimulation fMRI sessions, with higher functional activation (post > pre) for spoken words only following SMG stimulation, and for both spoken and written words following MTG stimulation, in regions associated with the reading network and additional cognitive and executive control regions.
Our results showed how a single-offline TMS session can modulate brain activity at ~20 minutes post-stimulation during spoken and written word processing. The selective contribution of the SMG stimulation for auditory (spoken) word processing provides further evidence of the distinct role of the dorsal and ventral streams within the reading network. These findings could contribute to the development of neuromodulatory interventions for individuals with reading and language impairments.
No: NCT04041960. Registered 29 July, 2019, https://clinicaltrials.gov/study/NCT04041960?cond=NCT04041960&rank=1 .
Research has indicated that general anesthetics may potentially induce neuroapoptosis, resulting in long-term neurological deficits in the developing brain. Fortunately, xenon, a noble gas, emerges as a promising candidate for an ideal anesthetic due to its favorable properties, offering neuroprotection and mitigating the neurotoxic effects of other general anesthetics during early life stages. Nevertheless, it is important to highlight that xenon has also been observed to cause neuroapoptosis in the neonatal brain, suggesting that xenon possesses both neuroprotective qualities (as evidenced by pre-clinical and clinical studies) and neurotoxic potential (based mainly on pre-clinical evidence) during brain development. To gain a comprehensive understanding the effects xenon, this review will explore the anesthetic properties of xenon, examine its effects on anesthesia, and elucidate its mechanisms of potential neuroprotection and neurotoxicity in the developing brain. The primary emphasis will be on xenon’s application in the context of anesthetic-induced developmental neurotoxicity (AIDN), hypoxic-ischemic encephalopathy (HIE), and teratogenicity, aiming to provide valuable insights for pediatricians, pediatric anesthesiologists, and other healthcare professionals involved in the use and study of xenon anesthesia.
Sleep disturbance and autonomic dysfunction are often found in Parkinson’s disease (PD) patients, but little is known about changes in cyclic alternating patterns (CAPs) of electroencephalographic (EEG) activities and heart rate variability (HRV) during deep sleep in PD patients.
To investigate changes in EEG activities and HRV during CAPs and non-CAPs (NCAPs) of N3 sleep in PD patients.
Polysomnographic (PSG) examinations were carried out on 18 PD patients and 18 healthy controls, and power spectral analysis of EEG activities and HRV during CAPs and NCAPs (the segment of sleep without CAPs for more than 60 seconds) of N3 sleep were carried out.
The percentages of N3 sleep with CAPs and CAP A1, as well as the CAP A1 index in the PD patients, were significantly smaller compared with the healthy controls. In addition, the power of α waves in NCAPs was significantly higher, while the powers of δ waves in Phase A and B of CAP A1 and A3, and NCAPs were significantly smaller. Furthermore, the durations of total δ waves and δ waves with an amplitude ≥75 μV were significantly shorter, and the low frequency (LF) power of HRV during CAPs and the LF/high frequency (HF) HRV ratio during both CAPs and NCAPs were significantly smaller.
The changes documented in EEG activities and HRV in PD patients during CAPs and NCAPs of N3 sleep compared with healthy controls suggest that N3 sleep quality and sympathetic function are compromised in PD patients.
Ischemic stroke (IS) constitutes a major threat to human health. Vascular recanalization by intravenous thrombolysis and mechanical thrombolysis remain the most significant and effective methods for relief of ischemia. Key elements of these treatments include achieving blood-vessel recanalization, restoring brain-tissue reperfusion, and preserving the ischemic penumbra. However, in achieving the therapeutic goals of vascular recanalization, secondary damage to brain tissue from cerebral ischemia-reperfusion injury (CIRI) must also be addressed. Despite advancements in understanding the pathological processes associated with CIRI, effective interventions to prevent its onset and progression are still lacking. Recent research has indicated that mitophagy and ferroptosis are critical mechanisms in the development of CIRI, and significantly contribute to the onset and progression of IS and CIRI because of common targets and co-occurrence mechanisms. Therefore, exploring and summarizing the potential connections between mitophagy and ferroptosis during CIRI is crucial. In the present review, we mainly focused on the mechanisms of mitochondrial autophagy and ferroptosis, and their interaction, in the development of CIRI. We believe that the data show a strong relationship between mitochondrial autophagy and ferroptosis with interactive regulation. This information may underpin new potential approaches for the prevention and treatment of IS and subsequent CIRI.
The study investigated the neural correlates of mind wandering using eyeblink rate (EBR) and variability (EBV) proxies. Dopamine, a neurotransmitter integral to the brain’s reward system, has been implicated in regulating both task-unrelated and task-focused thinking. This study sought to clarify the relationships between dopaminergic function and cognitive control during a task by utilizing EBR and EBV as proxy measures.
Vertical electrooculogram and brain event-related potential (ERP) data were gathered from 24 adult participants while they performed a computerized cognitive task. During the task (3-stimulus visual oddball procedure), participants discriminated between an infrequently seen target stimulus, an infrequent novel stimulus (for evaluating task engagement and distraction), and a commonly occurring nontarget stimulus. A retrospective questionnaire (Dundee Stress State Questionnaire, DSSQ) assessed task-unrelated (TUT) and task-related (TRT) thinking directly after task completion. The P3a ERP brain indexes at the Cz and Fz scalp electrode sites were also considered as a secondary proxy measure of dopamine function.
The main finding revealed that higher EBR was associated with higher TUT, suggesting a link between elevated dopaminergic activity and mind wandering. There was also a marginal negative correlation with P3a latency at the Fz scalp location and TUT, indicative of heightened responsiveness to distraction in general. For TRT, there was a positive correlation with P3a amplitudes at Fz, suggesting a role in task-related engagement and focus on all stimuli during the task. Regarding behavior, EBR and EBV were negatively correlated with Sigma ex-Gaussian task reaction time (RT), suggesting that more stable cognitive states are associated with higher blink rates and variability. Tau RT positively correlated with blink variability and P3a amplitudes at Fz and Cz, indicative of attentional lapse. Regression analyses showed that EBR and Mu RT predicted TUT, while TRT was predicted by P3a amplitude at Fz. More blinks and slower responses were related to TUT, whereas greater focus on the task stimuli (P3a amplitude) was related to TRT.
These data underscore the importance of dopamine during mind wandering and task focus. In addition, this study argues for using ex-Gaussian analysis to understand the complex dynamics of attentional control during mind wandering.
While vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains crucial, neurological complications have been detected following the coronavirus disease 2019 (COVID-19) vaccination. The neurological complications of COVID-19 vaccination can be seen in both the central nervous system (CNS) and the peripheral nervous system (PNS). In this study, we reviewed PNS complications after COVID-19 vaccination, their underlying mechanisms, diagnosis, and management. Inflammatory polyneuropathy, small fiber neuropathy, Parsonage-Turner syndrome (PTS), cranial mononeuropathies, and myasthenia gravis (MG) have been reported following COVID-19 vaccination. Inflammatory polyneuropathy following COVID-19 vaccination should be diagnosed early based on clinical presentation and treated with supportive care, and immunoglobulin or plasmapheresis to prevent respiratory distress if required. It is important to differentiate peripheral from central facial paralysis after COVID-19 vaccination to rule out upper motor neuron damage, including stroke. Diagnosis of small fiber neuropathy in the setting of COVID-19 vaccination should be suspected in patients with dysesthesia, dysautonomia, and lower extremity paresthesia. A skin biopsy of the proximal or distal lower limb should generally be considered for diagnosing small fiber neuropathy following COVID-19 vaccination. Even though pain at the injection site is one of the most common symptoms after COVID-19 vaccination, shoulder pain lasting more than 3 weeks should raise the suspicion of severe complications such as PTS. In addition to a proper physical examination as a reliable diagnosis tool, needle electromyography can be considered to help the diagnosis of PTS following COVID-19 vaccination. In our opinion, despite complications after COVID-19 vaccination, the benefit of vaccination immunity should not be forgotten.
Complete spinal cord injury (SCI) leads to a disconnection between the brain and the body below the injury level, resulting in the functional silencing, degeneration, and apoptosis of sensorimotor cortex (SMC) neurons, which is of crucial importance to the pathological process.
In this study, a rat model of spinal cord transection was employed to explore the activation of neurons in the SMC and the reversal of neurodegeneration after the rats were treated with transcranial intermittent theta-burst stimulation (T-iTBS).
The results demonstrated that the expression of the immediate early gene c-Fos and the synaptic plasticity-associated activity-regulated cytoskeleton (Arc) gene in the neurons of the SMC was increased in the T-iTBS group 4 weeks after SCI. Transcriptome sequencing revealed that neuronal activation-, neuronal metabolism-, synaptic activity-, and neural regeneration-related genes were significantly upregulated in the T-iTBS group compared with those of the sham-iTBS group, but the expression was similar to that in the normal group. Western blot analysis indicated that the expression of Cle-caspase-3 (CC3) in the SMC was significantly reduced in the T-iTBS group, and the number of CD68-positive cells in the SMC was close to that of normal rats but significantly less than that in the sham-iTBS and SCI groups. These results are in line with those of the transcriptome sequencing. Correlation analysis of the expression rate between c-Fos and Arc, CC3, and CD68 further suggested that T-iTBS improved the immune microenvironment and prevented neurodegeneration by regulating the activation and synaptic plasticity of SMC neurons in the early stages of injury.
Collectively, our findings offer support for the utilization of T-iTBS, a non-invasive neural stimulation treatment, to prevent SMC degeneration following severe SCI.
Schizophrenia (SCZ) is associated with abnormal neural activities and brain connectivity. Electroencephalography (EEG) microstate is a voltage topographical representation of temporary brain network activations. Most research on EEG microstates in SCZ has focused on differences between patients and healthy controls (HC). However, changes in EEG microstates among SCZ patients across various stages of physiological and cognitive development have not been thoroughly assessed. Consequently, we stratified patients with SCZ into four age-specific cohorts (20–29 years (brain maturation), 30–39 years (stabilization), 40–49 years (early aging), and 50–59 years (advanced aging)) to evaluate EEG microstate alterations. Additionally, we assessed changes in EEG microstates in first-episode psychosis (FEP) before and after an 8-week treatment period.
We acquired 19-channel resting-state EEG from 140 chronic SCZ patients, aged 20 to 59 years, as well as from 19 FEP and 20 healthy controls. FEP patients underwent an 8-week inpatient follow-up. After pre-processing, EEG data from different groups were subjected to microstate analysis, and the K-Means clustering algorithm was applied to classify the data into 4 microstates. Subsequently, templates of these microstates were used to fit EEG signals from each patient, and the collected microstate parameters were analyzed.
Patients with SCZ aged 20 to 29 years demonstrated an increased time coverage of microstate class D compared to other age cohorts. In individuals aged 30–39 years, the parameters of microstate class B—specifically time coverage and occurrence—exhibited significant reductions relative to those in the 40–49 and 50–59 years age groups. Compared to healthy controls, microstates class A parameters were significantly reduced in SCZ patients, while microstates class C parameters were prolonged; after 8 weeks of treatment, microstates class A parameters increased and microstates class C parameters decreased.
Alterations in microstate dynamics were observed among SCZ patients across developmental stages, suggesting potential changes in brain activity patterns. Changes in microstates A and C may serve as potential biomarkers for evaluating treatment efficacy, establishing a foundation for personalized therapeutic approaches.
This study aimed to investigate the effects of transcranial direct current stimulation (tDCS) on brain functional networks in children with autism spectrum disorder (ASD).
We constructed brain functional networks using phase-locking value (PLV) and assessed the temporal variability of these networks using fuzzy entropy. Graph theory was applied to analyze network characteristics. Resting-state electroencephalography (EEG) data were used to compare differences in brain functional connectivity, temporal variability, and network properties between children with ASD and typically developing (TD) children. Additionally, we examined the changes in functional connectivity, temporal variability, and network properties in children with ASD after 20 sessions of tDCS intervention.
The study revealed that children with ASD exhibited lower connectivity in the alpha band and higher connectivity in the beta band. In the delta and theta bands, ASD children demonstrated a mixed pattern of both higher and lower connectivity. Furthermore, ASD children exhibited higher temporal variability across all four frequency bands, particularly in the delta and beta bands. After tDCS intervention, the total score of the Autism Behavior Checklist (ABC) significantly decreased. Additionally, functional connectivity in the delta and alpha bands increased, while temporal variability in the delta and beta bands decreased, indicating positive changes in brain network characteristics.
These results suggest that tDCS may be a promising intervention for modulating brain functional networks in children with ASD.
ChiCTR2400092790. Registered 22 November, 2024, https://www.chictr.org.cn/showproj.html?proj=249950.