Neural Plasticity最新文献

Objective: Volume reduction and structural abnormality is the most replicated finding in neuroimaging studies of Alzheimer's disease (AD). Amnestic mild cognitive impairment (aMCI) is the early stage of AD development. Thus, it is necessary to investigate the link between atrophy of regions of interest (ROIs) in medial temporal lobe, the variation trend of ROI densities and volumes among patients with cognitive impairment, and the distribution characteristics of ROIs in the aMCI group, Alzheimer's disease (AD) group, and normal control (NC) group.

Methods: 30 patients with aMCI, 16 patients with AD, and 30 NC are recruited; magnetic resonance imaging (MRI) brain scans are conducted. Voxel-based morphometry was employed to conduct the quantitative measurement of gray matter densities of the hippocampus, amygdala, entorhinal cortex, and mammillary body (MB). FreeSurfer was utilized to automatically segment the hippocampus into 21 subregions and the amygdala into 9 subregions. Then, their subregion volumes and total volume were calculated. Finally, the ANOVA and multiple comparisons were performed on the above-mentioned data from these three groups.

Results: AD had lower GM densities than MCI, and MCI had lower GM densities than NC, but not all of the differences were statistically significant. In the comparisons of AD-aMCI-NC, AD-aMCI, and AD-NC, the hippocampus, amygdala, and entorhinal cortex showed differences in the gray matter densities (p < 0.05); the differences of mammillary body densities were not significant in the random comparison between these three groups (p > 0.05). The hippocampus densities and volumes of the subjects from the aMCI group and the AD group were bilaterally symmetric. The gray matter densities of the right side of the entorhinal cortex inside each group and the hippocampus from the NC group were higher than those of the left side (p < 0.05), and the gray matter densities of the amygdala and mammillary body were bilaterally symmetric in the three groups (p > 0.05). There were no gender differences of four ROIs in the AD, aMCI, and NC groups (p > 0.05). The volume differences of the hippocampus presubiculum-body and parasubiculum manifest no statistical significance (p > 0.05) in the random comparison between these three groups. Volume differences of the left amygdala basal nucleus, the left lateral nucleus, the left cortical amygdala transitional area, the left paravamnion nucleus, and bilateral hippocampal amygdala transition area (HATA) had statistical differences only between the AD group and the NC group (p < 0.05).

Conclusion: Structural defects of medial temporal lobe subfields were revealed in the aMCI and AD groups. Decreased gray matter densities of the hippocampus, entorhinal cortex, and amygdala could distinguish patients with early stage of AD between aMCI and NC. Volume d

Background: The aim was to investigate the influence of propionic acid (PA) on the endoplasmic reticulum (ER), unfolded protein response (UPR) state, and astrocyte/microglia markers in rat ventromedial hypothalamus (VMH) after type 2 diabetes mellitus (T2DM).

Methods: Male Wistar rats were divided: (1) control, (2) T2DM, and groups that received the following (14 days, orally): (3) metformin (60 mg/kg), (4) PA (60 mg/kg), and (5) PA+metformin. Western blotting, RT-PCR, transmission electron microscopy, and immunohistochemical staining were performed.

Results: We found T2DM-associated enlargement of ER cisterns, while drug administration slightly improved VMH ultrastructural signs of damage. GRP78 level was 2.1-fold lower in T2DM vs. control. Metformin restored GRP78 to control, while PA increased it by 2.56-fold and metformin+PA-by 3.28-fold vs. T2DM. PERK was elevated by 3.61-fold in T2DM, after metformin-by 4.98-fold, PA-5.64-fold, and metformin+PA-3.01-fold vs. control. A 2.45-fold increase in ATF6 was observed in T2DM. Metformin decreased ATF6 content vs. T2DM. Interestingly, PA exerted a more pronounced lowering effect on ATF6, while combined treatment restored ATF6 to control. IRE1 increased in T2DM (2.4-fold), metformin (1.99-fold), and PA (1.45-fold) groups vs. control, while metformin+PA fully normalized its content. The Iba1 level was upregulated in T2DM (5.44-fold) and metformin groups (6.88-fold). Despite PA treatment leading to a further 8.9-fold Iba1 elevation, PA+metformin caused the Iba1 decline vs. metformin and PA treatment. GFAP level did not change in T2DM but rose in metformin and PA groups vs. control. PA+metformin administration diminished GFAP vs. PA. T2DM-induced changes were associated with dramatically decreased ZO-1 levels, while PA treatment increased it almost to control values.

Conclusions: T2DM-induced UPR imbalance, activation of microglia, and impairments in cell integrity may trigger VMH dysfunction. Drug administration slightly improved ultrastructural changes in VMH, normalized UPR, and caused an astrocyte activation. PA and metformin exerted beneficial effects for counteracting diabetes-induced ER stress in VMH.

Sensorineural hearing loss (SNHL) is one of the most common causes of disability worldwide. Previous evidence suggests that reactive oxygen species (ROS) may play an important role in the occurrence and development of SNHL, while its mechanism remains unclear. We cultured dissected organs of Corti in medium containing different concentrations (0, 0.25, 0.5, 0.75, 1, and 1.25 mM) of hydrogen peroxide (H₂O₂) and established a four-concentration model of 0, 0.5, 0.75, and 1 mM to study different degrees of damage. We examined ROS-induced mitochondrial damage and the role of sirtuin 3 (SIRT3). Our results revealed that the number of ribbon synapses and hair cells appeared significantly concentration-dependent decrease with exposure to H₂O₂. Outer hair cells (OHCs) and inner hair cells (IHCs) began to be lost, and activation of apoptosis of hair cells (HCs) was observed at 0.75 mM and 1 mM H₂O₂, respectively. In contrast with the control group, the accumulation of ROS was significantly higher, and the mitochondrial membrane potential (MMP) was lower in the H₂O₂-treated groups. Furthermore, the expression of SIRT3, FOXO3A, and SOD2 proteins declined, except for an initial elevation of SIRT3 between 0 and 0.75 mM H₂O₂. Administration of the selective SIRT3 inhibitor 3-(1H-1,2,3-triazol-4-yl) pyridine resulted in increased damage to the cochlea, including loss of ribbon synapses and hair cells, apoptosis of hair cells, more production of ROS, and reduced mitochondrial membrane potential. Thoroughly, our results highlight that ROS-induced mitochondrial oxidative damage drives hair cell degeneration and apoptosis. Furthermore, SIRT3 is crucial for preserving mitochondrial function and protecting the cochlea from oxidative damage and may represent a possible therapeutic target for SNHL.

Proprioceptive deficit is one of the common sensory impairments following stroke and has a negative impact on motor performance. However, evidence-based training procedures and cost-efficient training setups for patients with poststroke are still limited. We compared the effects of proprioceptive training versus nonspecific sensory stimulation on upper limb proprioception and motor function rehabilitation. In this multicenter, single-blind, randomized controlled trial, 40 participants with poststroke hemiparesis were enrolled from 3 hospitals in China. Participants were assigned randomly to receive proprioceptive training involving passive and active movements with visual feedback (proprioceptive training group [PG]; n = 20) or nonspecific sensory stimulation (control group [CG]; n = 20) 20 times in four weeks. Each session lasted 30 minutes. A clinical assessor blinded to group assignment evaluated patients before and after the intervention. The primary outcome was the change in the motor subscale of the Fugl-Meyer assessment for upper extremity (FMA-UE-M). Secondary outcomes were changes in box and block test (BBT), thumb localization test (TLT), the sensory subscale of the Fugl-Meyer assessment for upper extremity (FMA-UE-S), and Barthel Index (BI). The results showed that the mean change scores of FMA-UE were significantly greater in the PG than in the CG (p = 0.010 for FMA-UE-M, p = 0.033 for FMA-UE-S). The PG group was improved significantly in TLT (p = 0.010) and BBT (p = 0.027), while there was no significant improvement in TLT (p = 0.083) and BBT (p = 0.107) for the CG group. The results showed that proprioceptive training was effective in improving proprioception and motor function of the upper extremity in patients with poststroke. This trial is registered in the Chinese Clinical Trial Registry (ChiCTR2000037808).

The mammalian hippocampal dentate gyrus is a niche for adult neurogenesis from neural stem cells. Newborn neurons integrate into existing neuronal networks, where they play a key role in hippocampal functions, including learning and memory. In the ageing brain, neurogenic capability progressively declines while in parallel increases the risk for developing Alzheimer's disease (AD), the main neurodegenerative disorder associated with memory loss. Numerous studies have investigated whether impaired adult neurogenesis contributes to memory decline in AD. Here, we review the literature on adult hippocampal neurogenesis (AHN) and AD by focusing on both human and mouse model studies. First, we describe key steps of AHN, report recent evidence of this phenomenon in humans, and describe the specific contribution of newborn neurons to memory, as evinced by animal studies. Next, we review articles investigating AHN in AD patients and critically examine the discrepancies among different studies over the last two decades. Also, we summarize researches investigating AHN in AD mouse models, and from these studies, we extrapolate the contribution of molecular factors linking AD-related changes to impaired neurogenesis. Lastly, we examine animal studies that link impaired neurogenesis to specific memory dysfunctions in AD and review treatments that have the potential to rescue memory capacities in AD by stimulating AHN.

Background: Contralaterally controlled neuromuscular electrical stimulation (CCNMES) is a novel electrical stimulation treatment for stroke; however, reports on the efficacy of CCNMES on lower extremity function after stroke are scarce.

Objective: To compare the effects of CCNMES versus NMES on lower extremity function and activities of daily living (ADL) in subacute stroke patients.

Methods: Forty-four patients with a history of subacute stroke were randomly assigned to a CCNMES group and a NMES group (n = 22 per group). Twenty-one patients in each group completed the study per protocol, with one subject lost in follow-up in each group. The CCNMES group received CCNMES to the tibialis anterior (TA) and the peroneus longus and brevis muscles to induce ankle dorsiflexion motion, whereas the NMES group received NMES. The stimulus current was a biphasic waveform with a pulse duration of 200 μs and a frequency of 60 Hz. Patients in both groups underwent five 15 min sessions of electrical stimulation per week for three weeks. Indicators of motor function and ADL were measured pre- and posttreatment, including the Fugl-Meyer assessment of the lower extremity (FMA-LE) and modified Barthel index (MBI). Surface electromyography (sEMG) assessments included average electromyography (aEMG), integrated electromyography (iEMG), and root mean square (RMS) of the paretic TA muscle.

Results: Values for the FMA-LE, MBI, aEMG, iEMG, and RMS of the affected TA muscle were significantly increased in both groups after treatment (p < 0.01). Patients in the CCNMES group showed significant improvements in all the measurements compared with the NMES group after treatment. Within-group differences in all post- and pretreatment indicators were significantly greater in the CCNMES group than in the NMES group (p < 0.05).

Conclusion: CCNMES improved motor function and ADL ability to a greater extent than the conventional NMES in subacute stroke patients.

Objective: To determine the long-term effects of low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) over the contralesional M1 preceding motor task practice on the interhemispheric asymmetry of the cortical excitability and the functional recovery in subacute stroke patients with mild to moderate arm paresis.

Methods: Twenty-four subacute stroke patients were randomly allocated to either the experimental or control group. The experimental group underwent rTMS over the contralesional M1 (1 Hz), immediately followed by 30 minutes of motor task practice (10 sessions within 2 weeks). The controls received sham rTMS and the same task practice. Following the 2-week intervention period, the task practice was continued twice weekly for another 10 weeks in both groups. Outcomes were evaluated at baseline (T0), at the end of the 2-week stimulation period (T1), and at 12-week follow-up (T2).

Results: The MEP (paretic hand) and interhemispheric asymmetry, Fugl-Meyer motor assessment, Action Research Arm Test, and box and block test scores improved more in the experimental group than controls at T1 (p < 0.05). The beneficial effects were largely maintained at T2.

Conclusion: LF-rTMS over the contralesional M1 preceding motor task practice was effective in enhancing the ipsilesional cortical excitability and upper limb function with reducing interhemispheric asymmetry in subacute stroke patients with mild to moderate arm paresis. Significance. Adding LF-rTMS prior to motor task practice may reduce interhemispheric asymmetry of cortical excitabilities and promote upper limb function recovery in subacute stroke with mild to moderate arm paresis.

Background: Visual symptoms are common in patients with migraine, even in interictal periods. The purpose was to assess the association between dynamic functional connectivity (dFC) of the visual cortex and clinical characteristics in migraine without aura (MwoA) patients.

Methods: We enrolled fifty-five MwoA patients as well as fifty gender- and age-matched healthy controls. Regional visual cortex alterations were investigated using regional homogeneity (ReHo) and amplitude of low-frequency fluctuation (ALFF). Then, significant regions were selected as seeds for conducting dFC between the visual cortex and the whole brain.

Results: Relative to healthy controls, MwoA patients exhibited decreased ReHo and ALFF values in the right lingual gyrus (LG) and increased ALFF values in the prefrontal cortex. The right LG showed abnormal dFC within the visual cortex and with other core brain networks. Additionally, ReHo values for the right LG were correlated with duration of disease and ALFF values of the right inferior frontal gyrus and middle frontal gyrus were correlated with headache frequency and anxiety scores, respectively. Moreover, the abnormal dFC of the right LG with bilateral cuneus was positively correlated with anxiety scores.

Conclusions: The dFC abnormalities of the visual cortex may be involved in pain integration with multinetworks and associated with anxiety disorder in episodic MwoA patients.

Voltage-gated sodium channel beta 2 (Nav2.2 or Navβ2, coded by SCN2B mRNA), a gene involved in maintaining normal physiological functions of the prefrontal cortex and hippocampus, might be associated with prefrontal cortex aging and memory decline. This study investigated the effects of Navβ2 in amyloid-β 1-42- (Aβ1-42-) induced neural injury model and the potential underlying molecular mechanism. The results showed that Navβ2 knockdown restored neuronal viability of Aβ1-42-induced injury in neurons; increased the contents of brain-derived neurotrophic factor (BDNF), enzyme neprilysin (NEP) protein, and NEP enzyme activity; and effectively altered the proportions of the amyloid precursor protein (APP) metabolites including Aβ42, sAPPα, and sAPPβ, thus ameliorating cognitive dysfunction. This may be achieved through regulating NEP transcription and APP metabolism, accelerating Aβ degradation, alleviating neuronal impairment, and regulating BDNF-related signal pathways to repair neuronal synaptic efficiency. This study provides novel evidence indicating that Navβ2 plays crucial roles in the repair of neuronal injury induced by Aβ1-42 both in vivo and in vitro.

Ketamine (KET) is widely used for induction and maintenance of anesthesia, and long-term use is required for treatment of depression patients. Repeated use of KET is associated with mood and memory disorders. Ulinastatin (UTI), a urinary trypsin inhibitor, has been widely undertaken as an anti-inflammatory drug and proved to have neuroprotective effects. The aim of this work was to determine whether prophylactic use of UTI could attenuate KET-induced cognitive impairment. It was found that repetitive KET anesthesia cause cognitive and emotional disorders in adolescent mice in WMZ and OFT test, while UTI pretreatment reversed the poor performance compared to the AK group, and the platform finding time and center crossing time were obviously short in the CK+UTI group (P < 0.05). Our ELISA experiment results discovered that UTI pretreatment reduced the expression levels of IL-1β and IL-6 induced by CK anesthesia compared to AK (P < 0.05). In addition, UTI pretreatment protected the cognitive function by restraining the expression levels of Tau protein, Tau phospho-396 protein, and Aβ protein in the CK group compared to the AK group in Western blotting (P < 0.05). The results suggested that UTI could act as a new strategy to prevent the neurotoxicity of KET, revealing a significant neuroprotective effect of UTI.