Neuroscience
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At the vertebrate neuromuscular junction (NMJ), presynaptic homeostatic potentiation (PHP) refers to an increase in neurotransmitter release that restores the strength of synaptic transmission following a blockade of nicotinic acetylcholine receptors (nAChRs). Mechanisms informing the presynaptic terminal of the loss of postsynaptic receptivity remain poorly understood. Previous research at the mouse NMJ suggests that extracellular protons may function as a retrograde signal that triggers an upregulation of neurotransmitter output (measured by quantal content, QC) through the activation of acid-sensing ion channels (ASICs). ⋯ In line with this hypothesis, we found that pharmacological inhibition of the PMCA with carboxyeosin induces QC upregulation and that this effect requires functional ASICs. We also demonstrated that muscles pre-treated with carboxyeosin fail to generate PHP. These findings suggest that reduced PMCA activity causes presynaptic homeostatic potentiation by activating ASICs at the mouse NMJ.
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Normal aging in mammals is accompanied by a decline in learning and memory. Dopamine plays a vital role in regulating cognitive functions, but it declines with age: During non-pathological aging, dopamine levels, receptors, and transporters decrease. Regarding the role of the dopaminergic system's changes in old age, we examined the effect of age and applied dopamine on working memory, synaptic transmission, and long-term potentiation (LTP) induction and maintenance in young adult and mature adult mice. ⋯ There was no difference in LTP induction and maintenance between young and mature adult mice before dopamine application. However, the application of dopamine on mature adult murine slices increased LTP magnitude compared to slices from young adults. According to the obtained results, it may be concluded that hippocampal neural excitability increased in mature adult subjects, and application of dopamine abolished the difference in neural excitability among young mature and adult mature groups; which was accompanied with increment of working memory and synaptic potentiation in mature adult animals.
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Previous study showed that electroacupuncture (EA) produced a protective effect on cerebral ischemia-reperfusion injury (CIRI) in rats and may correlate with the anti-inflammatory effects of microglia. This study aimed to investigate further whether EA could modulate neuroinflammation by targeting the Signal Transducer and Activator of Transcription 6 (STAT6) and Peroxisome Proliferator-Activated Receptor γ (PPARγ) pathway, the key regulator of microglia. Middle cerebral artery occlusion (MCAO) rats were used, and 6 h after reperfusion, EA interventions were performed in Chize (LU 5), Hegu (LI 4), Sanyinjiao (SP 6), and Zusanli (ST 36) on the affected side of the rats, the group that received EA + STAT6 phosphorylation inhibitor AS1517499 was used as a parallel control. ⋯ The data showed that EA significantly alleviated nerve injury, reduced infarct volume, enhanced the expression and activity of STAT6/PPARγ pathway, inhibited NF-κB activity, increased M2 microglia numbers and anti-inflammatory factor release, and inhibited microglia M1-type polarization and pro-inflammatory factor expression. In contrast, inhibition of STAT6 phosphorylation exacerbated neural damage, inhibited STAT6/PPARγ pathway activity, promoted microglia M1-type polarization and exacerbated neuroinflammation, resulting in an attenuated positive effect of EA intervention. Therefore, we concluded that EA intervention could attenuate microglia-associated neuroinflammation by enhancing the expression and activity of STAT6/PPARγ pathway, thereby reducing CIRI in MCAO rats.
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During the critical period of postnatal development, brain maturation is extremely sensitive to external stimuli. Newborn rodents already have functional somatosensory pathways and the thalamus, but the cortex is still forming. Immature thalamic synapses may produce large postsynaptic potentials in immature neurons, while non-synaptic membrane currents remain relatively weak and slow. ⋯ Inhibitory events prevented inactivation of action potentials and gamma-modulated neuronal firing. We conclude that the interplay of strong excitatory and inhibitory synapses and relatively weak intrinsic currents produces sensory-evoked early gamma oscillations in thalamocortical cells. We also propose that sensory-evoked large-amplitude excitatory events contribute to evoked spindle-bursts.
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Review
The biology, pathological roles of exosomes and their clinical application in Parkinson's disease.
Parkinson's disease (PD) is a neurodegenerative disease with a high global incidence and places a great burden on the patient, their family and society. Early diagnosis of PD is the key to hindering the progression process and may enable treatment to partially reverse the disease course. Exosomes are lipid bilayers with a diameter of 40-160 nm (average ∼100 nm), show a cup-shaped structure in transmission electron microscopy (TEM) images, and contain different types of nucleic acids and proteins. ⋯ Of course, exosomes also have great potential as drug delivery systems due to their low toxicity, lipid solubility and immunological inertness. However, there is still a lack of standardized, efficient, and ultrasensitive methods for the isolation of exosomes, hindering the development of effective biomarkers. Therefore, this review describes the biological characteristics of exosomes, exosome extraction methods, and the pathological role, diagnostic/therapeutic value of exosomes in PD.