The striatum plays a crucial role in providing input to the basal ganglia circuit and is implicated in the pathological process of Parkinson’s disease (PD). Disruption of the dynamic equilibrium in the basal ganglia loop can be attributed to the abnormal functioning of the medium spiny neurons (MSNs) within the striatum, potentially acting as a trigger for PD. Exercise has been shown to mitigate striatal neuronal dysfunction through neuroprotective and neurorestorative effects and to improve behavioral deficits in PD model mice. In addition, this effect is offset by the activation of MSNs expressing dopamine D2 receptors (D2-MSNs). In the current study, we investigated the underlying neurobiological mechanisms of this effect. Our findings indicated that exercise reduces the power spectral density of the beta-band in the striatum and decreases the overall firing frequency of MSNs, particularly in the case of striatal D2-MSNs. These observations were consistent with the results of molecular biology experiments, which revealed that aerobic training specifically enhanced the expression of striatal dopamine D2 receptors (D2R). Taken together, our results suggest that aerobic training aimed at upregulating striatal D2R expression to inhibit the functional activity of D2-MSNs represents a potential therapeutic strategy for the amelioration of motor dysfunction in PD.

Parkinson's disease (PD), a prevalent neurodegenerative condition, manifests predominantly through the degeneration of nigrostriatal dopaminergic (DA) pathways, culminating in a notable depletion of striatal dopamine. This pathophysiological process critically impairs the DA-mediated regulation of motor behaviors within the basal ganglia circuitry, particularly impacting various subtypes of striatal medium spiny neurons. Recent advancements in neuroscientific research have illuminated the pivotal role of D2-dopamine receptor expressing medium spiny neurons (D2-MSNs) plasticity in coordinating motor control in PD. Intriguingly, aerobic exercise emerges as a potent therapeutic intervention, capable of preventing or improving motor impairments. This ameliorative effect is mediated through the modulation of DA receptor activity and the consequent activation of downstream extracellular signal-regulated kinase (Erk) signaling pathway. This article meticulously reviewed the intricate regulatory mechanisms governing the structural and functional plasticity of striatal D2-MSNs in the context of PD. It particularly emphasized the transformative impact of aerobic exercise on motor deficits in PD, attributing this effect to the modulation of striatal D2-MSNs.

细胞外信号调节激酶1和2（Erk1/2）是一种丝氨酸/苏氨酸蛋白激酶，属于丝裂原活化蛋白激酶（MAPK）家族的关键成员，通过磷酸化细胞质和细胞核内的多种底物参与正常及病理状态下的细胞活动。以纹状体为核心的基底神经节（basal ganglia， BG）被认为是运动控制相关的重要结构。Erk1/2通过对纹状体胞外多巴胺（DA）和谷氨酸（Glu）信号进行整合，协调了细胞增殖、分化及转录和翻译等重要细胞事件。研究显示，纹状体多巴胺受体1型中等多棘神经元（D1-MSNs）和多巴胺受体2型中等多棘神经元（D2-MSNs）上，Erk/MAPK信号通路具有差异性调控运动行为的作用。纹状体D1-MSNs的Erk1/2通过多巴胺D1样受体(D 1 R)激活cAMP/PKA通路促进运动行为，D2-MSNs的Erk1/2通过多巴胺D2样受体(D 2 R)和α-氨-3-羟基-5-甲基-4-异恶唑丙酸受体（AMPAR）抑制运动行为。此外，Erk/MAPK信号通路还能参与调节帕金森病（PD）、亨廷顿病及成瘾行为相关的病理生理学进程。Erk/MAPK信号通路干预能够有效缓解相关运动功能障碍。因此，本文围绕Erk/MAPK信号通路对基底神经节运动行为调控的影响，以及该信号通路在PD等神经系统相关运动功能障碍发生中的分子生物学机制进行总结，为相关疾病的治疗及预防提供新的视角。

In Parkinson’s disease (PD) state, with progressive loss of dopaminergic neurons in the substantia nigra, the striatal dopamine (DA) and glutamate (Glu) levels change, resulting in dysfunction of basal ganglia motor regulation. The PD patient presents motor dysfunction such as resting tremor, bradykinesia, and muscular rigidity. To investigate the mechanism of aerobic exercise to improve PD-related motor dysfunction, in the current study, 6-hydroxydopamine (6-OHDA) was used to induce the PD mice model, and the motor function of PD mice was comprehensively evaluated by open-field test, rotarod test, and gait test. The co-expression of prodynorphin (PDYN) and proenkephalin (PENK) with extracellular signal-regulated kinase (Erk1/2) and phosphorylation Erk1/2 (p-Erk1/2) were detected by double-labeling immunofluorescence. The results showed that a 4-week aerobic exercise intervention could effectively improve the motor dysfunction of PD mice. Moreover, it was found that the expressions of Erk1/2 and p-Erk1/2 in the dorsal striatum (Str) of PD mice were significantly increased, and the number of positive cells co-expressed by Erk1/2, p-Erk1/2, and PENK was significantly higher than PDYN. The above phenomenon was reversed by a 4-week aerobic exercise intervention. Therefore, this study suggests that the mechanism by which aerobic exercise improves PD-related motor dysfunction may be related to that the aerobic exercise intervention alleviates the activity of extracellular signal-regulated kinase/mitogen-activated protein kinases (Erk/MAPK) signaling pathway in striatal medium spiny neurons expressing D2-like receptors (D2-MSNs) of PD mice by regulating the striatal DA and Glu signaling.

Visceral obesity is one of the key features of metabolic syndrome. High-intensity interval training (HIIT) could effectively reduce visceral fat, but its effects show strong heterogeneity in populations with different degrees of obesity. The mechanism may be related to the differential adaptation to training between obesity phenotypes, namely obesity prone (OP) and obesity resistant (OR). The aim of the present study was to compare adaptive changes of visceral adipose lipolysis adaptation to HIIT between OP and OR animals and further explore the upstream pathway. OP and OR Sprague Dawley rats were established after feeding a high-fat diet for 6 weeks; they were then divided into HIIT (H-OP and H-OR) and control (C-OP and C-OR) groups. After 12 weeks of HIIT or a sedentary lifestyle, animals were fasted for 12 h and then sacrificed for histology as well as gene and protein analysis. Visceral adipocytes were isolated without fasting for catecholamine stimulation and β3-adrenergic receptor (β3-AR) blockade in vitro to evaluate the role of upstream pathways. After training, there were no differences in weight loss or food intake between OP and OR rats (P > 0.05). However, the visceral fat mass, adipocyte volume, serum triglycerides and liver lipids of OP rats decreased by more than those of OR rats (P < 0.05). Meanwhile, the cell lipolytic capacity and the increase in the expression of β3-AR were higher in the OP compared with OR groups (P < 0.05). Although training did not increase sympathetic nervous system activity (P > 0.05), the cell sensitivity to catecholamine increased significantly in the OP compared with OR groups (P < 0.05). Following blocking β3-AR, the increased sensitivity disappeared. With HIIT, OP rats lost more visceral fat than OR rats, which was related to stronger adaptive changes in lipolysis. Increased β3-AR expression mediated this adaptation.

Inspired by the low energy consumption and highly parallel processing power of the biological neuromorphic system, the development of a brain‐inspired computing paradigm with electronic devices based artificial synapse may play an essential role in eliminating the Von Neumann bottleneck. Among candidate electronic devices, memristive devices have shown great potential for artificial synapse because of its tunable resistive switching (RS) behaviors. Herein, a biological synapse with solution‐processed MgO‐graphene oxide quantum dots (MgO‐GOQDs) based memristor is developed. The device exhibits highly controllable RS behavior owing to the enhancement of the local electric field by GOQDs and redox of GOQDs under electric fields. Moreover, essential biosynaptic functions including paired‐pulse facilitation, short‐term plasticity (STP)/long‐term plasticity (LTP), STP to LTP transition, and spike‐time‐dependent plasticity are successfully emulated. It is noteworthy that the device fabricated on a polyethylene terephthalate substrate also presents stable RS behavior after a large number of bending cycles. This study demonstrates the great potential of solution‐processed MgO–GOQD hybrid film on its application for the realization of flexible artificial neural networks.

近年来,中枢神经系统功能障碍所引发的阿尔茨海默病、帕金森病、抑郁症和肥胖症等众多脑健康问题受到广泛关注.内源性大麻素(endocannabinoid)是脑内一类重要的神经调质和调节能量稳态的关键活性因子,与多种神经退行性疾病及脑健康问题的发生发展密切相关,被视为众多中枢神经系统功能障碍的潜在干预靶点.大量研究显示,规律的运动锻炼可有效改善或缓解中枢神经系统功能障碍,降低阿尔茨海默病、帕金森病、抑郁症及肥胖的发生风险,对促进不同人群脑健康具有积极作用,而内源性大麻素系统可能参与其中.此外,内源性大麻素系统还可通过调节奖赏系统功能促进运动参与,与运动促进脑健康形成"良性循环".该文主要从内源性大麻素系统的结构与生物学功能、运动与内源性大麻素系统的互动关系、内源性大麻素系统在运动防治中枢神经系统功能障碍及肥胖中的作用等方面进行系统论述,为运动促进脑健康理论提供新的视角与研究思路.