Brain Research最新文献

This study investigated whether the cognitive benefits of intermittent theta-burst stimulation (iTBS) in post-stroke cognitive impairment (PSCI) are mediated through modulation of the cerebellar dentate nucleus-contralateral ventromedial thalamus (DN-VM) circuit. The PSCI mice model were created using photothrombotic stroke, and the animals were assigned to five groups: Sham, PSCI, PSCI + iTBS, PSCI + iTBS + chemogenetic inhibition, and PSCI + chemogenetic excitation. Each group received its corresponding intervention. Behavioral changes were assessed before and after the intervention, and local field potentials (LFPs) were recorded from the medial prefrontal cortex (mPFC) and ventral hippocampus (vHPC) using in vivo electrophysiology. We analyzed oscillatory power within each region, as well as interregional coherence and theta-gamma coupling between the mPFC and vHPC. After 21 days of cerebellar iTBS, PSCI mice showed significant improvements in Y-maze performance, accompanied by increased theta band power in both the mPFC and vHPC, as well as enhanced interregional coherence and theta-gamma coupling. When chemogenetic inhibition of DN-VM excitability was applied with iTBS, these improvements were markedly reduced. Conversely, 21 days of chemogenetic excitation of the DN-VM circuit produced behavioral and electrophysiological effects comparable to those observed in the iTBS group. These findings suggest that cerebellar iTBS improves post-stroke cognition in mice by modulating the DN-VM circuit. Furthermore, the DN-VM pathway appears closely associated with cognitive function and may serve as a novel neuromodulatory target for PSCI.

Alpha-band power is considered as a marker of sensory processing-related cortical states, including sensory suppression and the temporal organization of sensory input. This study aimed to investigate whether alpha-band power of electrophysiological brain responses is modulated by different interstimulus intervals during repetitive, non-painful tactile stimulation. Non-painful tactile stimuli were delivered to the index finger of the right hand with different interstimulus intervals (ISI) of 2 s (s), 4 s, and 8 s via a pneumatic stimulator. A separate session was conducted for each ISI in a pseudorandomized order. The electroencephalogram was recorded in all sessions with 24 volunteers. The results of the analysis showed that the alpha activity was lowest at ISI₄ and highest at ISI₈. This pattern was consistently observed in both the central and parietal regions. In the ISI₂ session, although no notable variation among the frontal, central, and parietal areas was observed, the most pronounced activity was observed in the frontal region in the ISI₄ session. The highest level of alpha activity was observed in the central area during the ISI₈ session. Variations in interstimulus intervals affect inhibitory control and sensory processing in the brain. The frontal cortex appears to manage attention and cognitive control more efficiently at intermediate intervals (ISI₄), whereas the central region shows greater involvement in processing tactile inputs at longer intervals (ISI₈).

Hydrogen sulfide (H₂S), known as a metabolic modulator, is a gaseous signaling molecule with functions similar to those of nitric oxide and carbon monoxide, all of which possess vasodilatory, antioxidant, and other properties. In the central nervous system, H₂S is a signaling molecule that is crucial for neuroprotection and the control of neurological processes. The paraventricular nucleus (PVN) of the hypothalamus is an important central nucleus that regulates and integrates cardiovascular and peripheral sympathetic activity. This study aimed to investigate whether intra-PVN injection of the endogenous H₂S synthase CBS activator S-adenosylmethionine (SAMe) or the endogenous H₂S synthase CBS inhibitor hydroxylamine (HA) modulates H₂S expression in the PVN, whether microglia in the PVN are targeted by H₂S, and whether PVN H₂S further induces alterations in blood pressure(BP) by affecting endoplasmic reticulum(ER) stress in the PVN of spontaneously hypertensive rats (SHR). Healthy male Wistar-Kyoto (WKY) rats and SHR were fed a normal diet for 8 weeks, followed by intra-PVN injections of SAMe, HA, or vehicle for 4 weeks. Plasma norepinephrine levels and mean arterial pressure were elevated in the SHR group. The expression of factors related to ER stress, such as p-PERK, GRP78, and p-IRE1α, was also elevated. Levels of these parameters were lower in the SHR + SAMe group, whereas the SHR + HA group presented with higher levels of these indicators. These findings suggest that endogenous H₂S attenuates sympathetic activity and hypertensive responses in the PVN, in part by modulating ER stress.

Ghrelin plays a crucial role in metabolism and gastrointestinal function. In the central nervous system, ghrelin modulates both hedonic and homeostatic control of eating behavior. Ghrelin promotes neuron survival by reducing apoptosis, inflammation, and oxidative stress, making it a potential therapeutic agent for neurodegenerative diseases. Parkinson's Disease (PD) is a neurodegenerative disease characterized by motor and non-motor symptoms. The motor impairments result primarily from the progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta. Individuals with PD exhibit reduced levels of fasting and postprandial plasma ghrelin, and its receptors (GHSR) are expressed in the substantia nigra. Thus, this review aimed to evaluate the effects of ghrelin or GHSR agonists administration in experimental models of PD. A systematic search was conducted across PubMed, Scopus, Web of Science, and Embase. The 12 included studies involved PD models induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), 6-hydroxydopamine (6-OHDA), as well as A53T transgenic mice. Interventions were performed with acylated and/or des-acylated ghrelin, in addition to the GHSR agonist HM01. Intervention with ghrelin was able to reduce dopaminergic neurodegeneration and improve motor function, while also positively impacting metabolic and gastrointestinal functions, expanding its relevance to non-motor consequences of PD. Considering that most results were obtained using acute toxin-induced models and only male animals, further studies using progressive PD models and evaluating sex differences are needed. Thus, although preclinical evidence supports ghrelin or GHSR agonists as promising agents for treatment, future studies will be essential to inform clinical translation and optimize therapeutic strategies for individuals with PD.

Depression is thought to emerge as a result of monoamine neuromodulators' deficiency in a specific central nervous system site. Tauroursodeoxycholic acid (TUDCA) has been found to have a protective role against diseases affecting the central nervous system. The potential effects of TUDCA on brain monoamine neurotransmitters in a stress-induced depression model have not been reported. We investigated the effects of TUCDA treatment on serotonin, norepinephrine and dopamine, catecholamine biosynthesis enzyme tyrosine hydroxylase (TH) and degrading enzyme monoamine oxidase A (MAO-A), NLRP3 and pro-inflammatory IL-1β in the hippocampus and mPFC of male rats subjected to chronic unpredictable mild stress (CUMS). Behavioral results demonstrated that TUDCA exhibits antidepressant and anxiolytic properties. TUDCA treatment markedly reduced the stress-increased the levels of IL-1β and NLRP3 in the hippocampus and mPFC of CUMS rats. Results showed that TUDCA treatment failed to alter serotonin levels in the hippocampus and mPFC, whereas it restored reduced dopamine and norepinephrine in the hippocampus and ameliorated dopamine imbalance in the mPFC of stressed rats. Further analysis showed that TUDCA treatment increases TH expression in the hippocampus and reduces the increased the protein levels of MAO-A in both brain areas. Our research suggests that TUDCA mitigated depressive-like behavior, and the mechanism appeared to be related to the regulation of catecholamine levels and their synthetic and degrading enzymes in both brain areas.

Cholesterol is a major astrocyte-derived substance that reprograms neuronal lipid metabolism and regulates neuronal function upon uptake by neurons. However, the mechanisms controlling cholesterol biosynthesis and secretion in astrocytes remain poorly understood. Here, we show that hepaCAM, an astrocytic membrane protein, is essential for normal memory function in mice by maintaining synaptic protein levels and synaptic spine density. Mechanistically, hepaCAM promotes neuronal function by modulating SREBP2-dependent cholesterol biosynthesis in astrocytes and facilitating its subsequent secretion. Furthermore, we identify the interaction of hepaCAM and ClC-2 is required for hepaCAM's regulatory role in cholesterol biosynthesis. Knockdown of hepaCAM in the hippocampus leads to reduced synaptic protein levels, decreased spine density, and impaired memory in mice. Collectively, our findings demonstrate that astrocytic hepaCAM regulates memory function through modulation of the astrocytic cholesterol biosynthesis pathway.