Experimental Brain Research

Chandrababu, Krishnapriya; Radhakrishnan, Vineeth; Anjana, A. S.; Rajan, Rahul; Sivan, Unnikrishnan; Krishnan, Syam; Baby Chakrapani, P. S.

doi: 10.1007/s00221-023-06735-1pmid: 38015243

Parkinson's disease (PD) is a neurodegenerative disorder, prevalent in the elderly population. Neuropathological hallmarks of PD include loss of dopaminergic cells in the nigro-striatal pathway and deposition of alpha-synuclein protein in the neurons and synaptic terminals, which lead to a complex presentation of motor and non-motor symptoms. This review focuses on various aspects of PD, from clinical diagnosis to currently accepted treatment options, such as pharmacological management through dopamine replacement and surgical techniques such as deep brain stimulation (DBS). The review discusses in detail the potential of emerging stem cell-based therapies and gene therapies to be adopted as a cure, in contrast to the present symptomatic treatment in PD. The potential sources of stem cells for autologous and allogeneic stem cell therapy have been discussed, along with the progress evaluation of pre-clinical and clinical trials. Even though recent techniques hold great potential to improve the lives of PD patients, we present the importance of addressing the safety, efficacy, ethical, cost, and regulatory concerns before scaling them to clinical use.

Shen, Yufei; Zhu, Zhuoying; Wang, Yanping; Qian, Shuxia; Xu, Congying; Zhang, Baorong

doi: 10.1007/s00221-023-06709-3pmid: 37910178

Parkinson’s disease (PD) is one of the most common and complex Neurodegeneration, with an inherited metabolic disorder. Fibroblast growth factor 21 (FGF21), an endocrine hormone that belongs to the fibroblast growth factor superfamily, plays an extensive role in metabolic regulation. However, our understandings of the specific function and mechanisms of FGF21 on PD are still quite limited. Here, we aimed to elucidate the actions and the underlying mechanisms of FGF21 on dopaminergic neurodegeneration using cellular models of parkinsonism. To investigate the effects of FGF21 on dopaminergic neurodegeneration in vitro, proteasome impairment models of PD were utilized. Human dopaminergic neuroblastoma SH-SY5Y cells were treated with the proteasome inhibitor lactacystin (5 μmol/L) for 12 h, then with 50 ng/ml FGF-21 with or without 5 mmol/L of 3-methyladenine.The cells were dissected to assess alterations in autophagy using immunofluorescence, immunoblotting and electron microscopy assays. Our data indicate that FGF21 prevents dopaminergic neuron loss and shows beneficial effects against proteasome impairment induced PD syndrome, indicating it might be a potent candidate for developing novel drugs to deal with PD.

Jiang, Wei; Jia, Qingge; Ma, Hongxin; Han, Song; Bi, Shijun; Zhu, Kunyuan; Chen, Ligang; Liang, Guobiao

doi: 10.1007/s00221-023-06682-xpmid: 37932484

Spontaneous subarachnoid hemorrhage (SAH) accounts for approximately 5% of all cases of stroke. SAH is correlated with elevated rates of mortality and disability. Despite significant advancements in comprehending the pathogenesis and surgical management, efficacious clinical interventions remain restricted, and the prognosis is yet to be enhanced. MicroRNAs play a crucial role in various pathological processes in organisms. Revealing these regulatory processes is conducive to the development of new treatment methods. MicroRNA-124 is highly expressed in the nervous system and has significant research value for SAH. This study aims to explore the role of miR-124 in the early post-SAH period on neural function and verify whether it is involved in the pathological and physiological processes of SAH. In this study, we used methods such as comparing the expression levels of miR-124 in cerebrospinal fluid, establishing a rat SAH model, and a mouse embryonic primary neuron hemoglobin stimulation model to verify the downstream proteins of miR-124 in SAH. Through transfection techniques, we adjusted the expression of this small RNA in Vitro and in Vivo models using miR-124 inhibitor and mimic in the primary neuron hemoglobin stimulation model and rat SAH model, and observed the phenotype. Finally, by consulting the literature and verifying in Vivo and in Vitro methods, AK4 and downstream molecule ATF3 were identified as downstream targets of miR-124.

Ishida, Tomomi; Nittono, Hiroshi

doi: 10.1007/s00221-023-06726-2pmid: 37947851

Omitted stimulus potentials (OSPs) occur when a sensory stimulus is unexpectedly omitted. They are thought to reflect predictions about upcoming sensory events. The present study examined how OSPs differ across the sensory modalities of predicted stimuli. Twenty-nine university students were asked to press a mouse button at a regular interval of 1–2 s, which was immediately followed by either a visual or auditory stimulus in different blocks. The stimuli were sometimes omitted (p = 0.2), to which event-related potentials (ERPs) were recorded. The results showed that stimulus omissions in both modalities elicited ERP waveforms consisting of three components, oN1, oN2, and oP3. The peak latencies of these components were shorter in the auditory modality than in the visual modality. The amplitudes of OSPs were larger when participants were told that the omission indicated their poor performance (i.e., they pressed a button at an irregular interval) than when it was irrelevant to their performance. These findings suggest that OSPs occur from around 100 ms in a modality-specific manner and increase in amplitude depending on the task relevance of stimulus omissions.

Eschelmuller, Gregg; Szarka, Annika; Gandossi, Braelyn; Inglis, J. Timothy; Chua, Romeo

doi: 10.1007/s00221-023-06727-1pmid: 37955706

Tendon vibration is used extensively to assess the role of peripheral mechanoreceptors in motor control, specifically, the muscle spindles. Periodic tendon vibration is known to activate muscle spindles and induce a kinesthetic illusion that the vibrated muscle is longer than it actually is. Noisy tendon vibration has been used to assess the frequency characteristics of proprioceptive reflex pathways during standing; however, it is unknown if it induces the same kinesthetic illusions as periodic vibration. The purpose of the current study was to assess the effects of both periodic and noisy tendon vibration in a kinesthetic targeting task. Participants (N = 15) made wrist extension movements to a series of visual targets without vision of the limb, while their wrist flexors were either vibrated with periodic vibration (20, 40, 60, 80, and 100 Hz), or with noisy vibration which consisted of filtered white noise with power between ~ 20 and 100 Hz. Overall, our results indicate that both periodic and noisy vibration can induce robust targeting errors during a wrist targeting task. Specifically, the vibration resulted in an undershooting error when moving to the target. The findings from this study have important implications for the use of noisy tendon vibration to assess proprioceptive reflex pathways and should be considered when designing future studies using noisy vibration.

Sasaki, Ayuka; Aisawa, Anri; Takeuchi, Naoyuki

doi: 10.1007/s00221-023-06728-0pmid: 37955707

Backward walking training presents a great challenge to the physical and neural systems, which may result in an improvement in gait performance. Transcranial direct current electrical stimulation (tDCS), which can non-invasively enhance cortical activity, has been reported to strengthen corticomotor plasticity. We investigated whether excitatory tDCS over the primary motor cortex (M1) or the dorsolateral prefrontal cortex (DLPFC) enhances the effects of backward walking training in healthy participants. Thirty-six healthy participants (16 men and 20 women, mean age 21.3 ± 1.4 years) participated in this study. The participants were randomly assigned to one of the three tDCS groups (M1, DLPFC, and sham). They performed 5 min of backward walking training during 15 min of tDCS. We evaluated dual-task forward and backward walking performance before and after training. Both tDCS groups increased walking speed in the backward condition, but the DLPFC group increased the dual-task backward walking speed more than the M1 group. The M1 group showed decreased gait variability in dual-task backward walking, whereas the DLPFC group showed increased gait variability. Backward walking training combined with M1 stimulation may increase the backward walking speed by reducing gait variability. Backward walking training combined with DLPFC stimulation may prioritize walking speed over gait stability. Our results indicate that backward walking training combined with tDCS may be extended to other rehabilitation methods to improve gait performance.

Akbari-Lalimi, Hossein; Naseri, Shahrokh; Momennezhad, Mahdi; Zare, Hoda; Talaei, Ali; Shafiei, Seyed Ali

doi: 10.1007/s00221-023-06712-8pmid: 37962638

The attention networks test (ANT) is frequently utilized to evaluate executive, alerting, and orienting attentional components. Additionally, it serves as an activation task in neuroimaging studies. This study aimed to examine the relationship between attention networks and brain electrophysiology. The study enrolled 40 right-handed male students (age = 20.8 ± 1.3 years) who underwent the revised attention network test, while their electroencephalogram signals were recorded. The study aimed to explore the effects of attention networks and their efficiencies on brain electrophysiology. The results indicated that the P3 amplitude was modulated by the conflict effect in the central (p-value = 0.014) and parietal (p-value = 0.002) regions. The orienting component significantly influenced P1 and N1 latencies in the parietal and parieto-occipital regions (p-values < 0.006), as well as P1 and N1 amplitude in the parieto-occipital region (p-values = 0.017 and 0.011). The alerting component significantly affected P1 latency and amplitude in the parietal and parieto-occipital regions, respectively (p-value = 0.02). Furthermore, N1 amplitude and the time interval between P1 and N1 were significantly correlated with the efficiency of alerting and orienting networks. In terms of connectivity, the coherence of theta and alpha bands significantly decreased in the incongruent condition compared to the congruent condition. Additionally, the effects of attention networks on event-related spectral perturbation were observed. The study revealed the influence of attention networks on various aspects of brain electrophysiology. Specifically, the alerting score correlated with the amplitude of the N1 component in the double-cue and no-cue conditions in the parieto-occipital region, while the orienting score in the same region correlated with the N1 amplitude in the valid cue condition and the difference in N1 amplitude between the valid cue and double-cue conditions. Overall, empirical evidence suggests that attention networks not only impact the amplitudes of electrophysiological activities but also influence their time course.

Mitsutake, Tsubasa; Nakazono, Hisato; Shiozaki, Tomoyuki; Fujita, Daisuke; Sakamoto, Maiko

doi: 10.1007/s00221-023-06731-5pmid: 37966504

Vestibular nuclei and cerebellar function comprise vestibular neural networks that control vestibular-related responses. However, the vestibular-related responses to simultaneous stimulation of these regions are unclear. This study aimed to examine whether the combination of noisy galvanic vestibular stimulation (nGVS) and cerebellar transcranial direct current stimulation (ctDCS) using a complex transcranial electrical stimulation device alters vestibular-dominant standing stability and vestibulo-ocular reflex (VOR) function. The center of foot pressure (COP) sway and VOR of participants (28 healthy, young adults) were assessed under four conditions of transcranial electrical stimulation using nGVS and ctDCS. The COP was calculated with the participant standing on a soft-foam surface with eyes closed using a force plate to evaluate body sway. VOR measurements were collected via passive head movements and fixation on a target projected onto the front wall using a video head impulse test (vHIT). VOR gain was calculated in six directions using a semicircular canal structure based on the ratio of eye movement to head movement. The nGVS + ctDCS and nGVS + sham ctDCS conditions decreased COP sway compared to the sham nGVS + ctDCS and sham nGVS + sham ctDCS conditions. No significant differences were observed in the main effect of stimulation or the interaction of stimulation and direction on the vHIT parameters. The results of this study suggest that postural stability may be independently affected by nGVS. Our findings contribute to the basic neurological foundation for the clinical application of neurorehabilitation using transcranial electrical stimulation of the vestibular system.

Zhu, Mengjiao; Long, Si; Tao, Yizhi; Zhang, Zhifa; Zhou, Zhiqiang; Wang, Xueren; Chen, Wei

doi: 10.1007/s00221-023-06730-6pmid: 37973625

Accumulating evidence indicates that microglia-mediated neuroinflammation in the hippocampus contributes to the development of perioperative neurocognitive disorder (PND). P38MAPK, a point of convergence for different signaling processes involved in inflammation, can be activated by various stresses. This study aims to investigate the role of the P38MAPK/ATF2 signaling pathway in the development of PND in mice. Aged C57BL/6 mice were subjected to tibial fracture surgery under isoflurane anesthesia to establish a PND animal model. The open field test was used to evaluate the locomotor activity of the mice. Neurocognitive function was assessed with the Morris water maze (MWM) and fear conditioning test (FCT) on postoperative days 1, 3 and 7. The mice exhibited cognitive impairment accompanied by increased expression of proinflammatory factors (IL-1β, TNF-α), proapoptotic molecules (caspase-3, bax) and microglial activation in the hippocampus 1, 3 and 7 days after surgery. Treatment with SB239063 (a P38MAPK inhibitor) decreased the expression of proinflammatory factors, proapoptotic molecules and Iba-1 in the CA1 region of the hippocampus. The number of surviving neurons was significantly increased. Inhibition of the P38MAPK/ATF2 signaling pathway attenuates hippocampal neuroinflammation and neuronal apoptosis in aged mice with PND, thus improving the perioperative cognitive function of the mice.

Nettinga, Jamie; Naseem, Sarah; Yakobi, Ofir; Willoughby, Teena; Danckert, James

doi: 10.1007/s00221-023-06733-3pmid: 37978080

Boredom is a prominent experience commonly reported in school settings and associated with poor academic achievement. Little is known, however, about the age-related trajectory of boredom. Here we examined self-reported ratings of boredom in a cross-sectional sample of 8 to 15-year olds (n = 185) as a function of resting state EEG. Results indicated that reports of boredom in school rose as a function of age. Resting state EEG showed a decrease in theta power with age perhaps reflective of increased control. While no effects were evident in beta and alpha bands, we did observe an interaction between boredom and age for frontal asymmetry such that for those higher in boredom, the asymmetry increased with age. Finally, for theta to beta ratios there were main effects of age (i.e., a decrease in theta/beta ratio with age) and boredom such that those higher in boredom had higher theta/beta ratios over frontal and central brain areas. The results are discussed in the context of prior work on school-related boredom and provide several important avenues for further research.