Xinjiang Kang

• Southwest Medical University

Animal models are crucial for elucidating the pathological mechanisms underlying Parkinson’s disease (PD). Unfortunately, most of transgenic mouse models fail to manifest pathological changes observed in PD patients, pending the advancement of PD research. However, the mechanism underlying this discrepancy remains elusive. Here, we provide compelli...

Sociosexual preference is critical for reproduction and survival. However, neural mechanisms encoding social decisions on sex preference remain unclear. In this study, we show that both male and female mice exhibit female preference but shift to male preference when facing survival threats; their preference is mediated by the dimorphic changes in t...

Dopamine (DA) in the striatum is vital for motor and cognitive behaviors. Midbrain dopaminergic neurons generate both tonic and phasic action potential (AP) firing patterns in behavior mice. Besides AP numbers, whether and how different AP firing patterns per se modulate DA release remain largely unknown. Here by using in vivo and ex vivo models, i...

Schizophrenia is a severe neuropsychiatric disease, but the initiation mechanisms are unclear. Although antipsychotics are effective against positive symptoms, therapeutic interventions for negative symptoms are limited due to the lack of pathophysiological mechanisms. Here we identify synaptotagmin-11 (Syt11) as a potential genetic risk factor and...

BACKGROUND The KCNQ1+KCNE1 (I Ks ) potassium channel plays a crucial role in cardiac adaptation to stress, in which β-adrenergic stimulation phosphorylates the I Ks channel through the cyclic adenosine monophosphate (cAMP)/PKA (protein kinase A) pathway. Phosphorylation increases the channel current and accelerates repolarization to adapt to an inc...

Endocytosis is a fundamental biological process that couples exocytosis to maintain the homeostasis of the plasma membrane and sustained neurotransmission. Super-resolution microscopy enables optical imaging of exocytosis and endocytosis in live cells and makes an essential contribution to understanding molecular mechanisms of endocytosis in neuron...

The central mechanisms underlying pain chronicity remain elusive. Here, we identify a reciprocal neuronal circuit in mice between the anterior cingulate cortex (ACC) and the ventral tegmental area (VTA) that mediates mutual exacerbation between hyperalgesia and allodynia and their emotional consequences and, thereby, the chronicity of neuropathic p...

The development of the cardiac conduction system (CCS) is essential for correct heart function. However, critical details on the cell types populating the CCS in the mammalian heart during the development remain to be resolved. Using single-cell RNA sequencing, we generated a large dataset of transcriptomes of ~0.5 million individual cells isolated...

Significance Precise and efficient coupling of endocytosis to exocytosis is critical for neurotransmission. The activity-dependent facilitation of endocytosis has been well established for efficient membrane retrieval; however, whether neural activity clamps endocytosis to avoid excessive membrane retrieval remains debatable with the mechanisms lar...

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Sympathetic neural remodeling, which involves the inflammatory response, plays an important role in ventricular arrhythmias (VAs) after myocardial infarction (MI). Adrenergic receptors on macrophages potentially modulate the inflammatory response. We hypothesized that the increased level of catecholamines activates macrophages and regulates sympath...

Parkinson’s disease is characterized by loss of dopamine neurons in the substantia nigra¹. Similar to other major neurodegenerative disorders, there are no disease-modifying treatments for Parkinson’s disease. While most treatment strategies aim to prevent neuronal loss or protect vulnerable neuronal circuits, a potential alternative is to replace...

Synaptotagmins (Syts) are well-established primary Ca²⁺ sensors to initiate presynaptic neurotransmitter release. They also play critical roles in the docking, priming, and fusion steps of exocytosis, as well as the tightly coupled exo-endocytosis, in presynapses. A recent study by Awasthi and others (2019) shows that Syt3 Ca²⁺-dependently modulate...

Co-release of multiple neurotransmitters from secretory vesicles is common in neurons and neuroendocrine cells. However, whether and how the transmitters co-released from a single vesicle are differentially regulated remains unknown. In matrix-containing dense-core vesicles (DCVs) in chromaffin cells, there are two modes of catecholamine (CA) relea...

α-synuclein (α-Syn) is a presynaptic enriched protein involved in the pathogenesis of Parkinson’s disease. However, the physiological roles of α-Syn remain poorly understood. Recent studies have indicated a critical role of α-Syn in the sensing and generation of membrane curvature during vesicular exocytosis and endocytosis. It has been known to mo...

Background: This study explored the neural differentiation and therapeutic effects of stem cells from human exfoliated deciduous teeth (SHED) in a rat model of Parkinson's disease (PD). Methods: The SHED were isolated from fresh dental pulp and were induced to differentiate to neurons and dopamine neurons by inhibiting similar mothers against dp...

Loss-of-function mutations in Parkin are the most common causes of autosomal recessive Parkinson's disease (PD). Many putative substrates of parkin have been reported; their pathogenic roles, however, remain obscure due to poor characterization, particularly in vivo. Here, we show that synaptotagmin-11, encoded by a PD-risk gene SYT11, is a physiol...

Neuronal communication and brain function mainly depend on the fundamental biological events of neurotransmission, including the exocytosis of presynaptic vesicles (SVs) for neurotransmitter release and the subsequent endocytosis for SV retrieval. Neurotransmitters are released through the Ca2+- and SNARE-dependent fusion of SVs with the presynapti...

Schizophrenia is a severely devastating mental disorder, the pathological process of which is proposed to be associated with the dysfunction of dopaminergic transmission. Our previous results have demonstrated slower kinetics of transmitter release (glutamate release in hippocampus and norepinephrine release in adrenal slice) in a schizophrenia mod...

Sympathetic nerve in heart is essential in cardiac physiology and diseases, because it releases catecholamines to regulate cardiac cells including ventricular myocytes, atrial myocytes and vas through GPCRs. With a modified glass-insulated micro carbon fiber electrode (pegCFE), we record stimulus (depolarization or hypoxia)-signals via either amper...

Aims/hypothesis: Insulin is a key metabolic regulator in health and diabetes. In pancreatic beta cells, insulin release is regulated by the major second messengers Ca(2+) and cAMP: exocytosis is triggered by Ca(2+) and mediated by the cAMP/protein kinase A (PKA) signalling pathway. However, the causal link between these two processes in primary be...

Significance With a combination of HPLC and carbon fiber electrodes, we demonstrate that grafted neural stem cells directly release dopamine in the damaged striatum in vivo and partially rescue a Parkinson’s disease (PD) model. ( i ) Primitive neural stem cell–dopamine-like neuron (pNSC–DAn) retained tyrosine hydroxylase expression and reduced the...

Classic calcium hypothesis states that depolarization-induced increase in intracellular Ca(2+) concentration ([Ca(2+)]i) triggers vesicle exocytosis by increasing vesicle release probability in neurons and neuroendocrine cells. The extracellular Ca(2+), in this calcium hypothesis, serves as a reservoir of Ca(2+) source. Recently we find that extrac...

Key points The timing of synaptic transmission is critical to synaptic plasticity in the striatum. However, the timing of striatal dopamine (DA) release induced by cholinergic interneurons (ChIs) in the striatum is unclear. In this study, we focused on the temporal components of DA release and replenishment triggered by different pathways. We show...

Striatal dopamine (DA) release can be independently triggered not only by action potentials (APs) in dopaminergic axons but also APs in cholinergic interneurons (ChIs). Nicotine causes addiction by modulating DA release, but with paradoxical findings. Here, we investigate how physiologically relevant levels of nicotine modulate striatal DA release....

The genetic manipulation of the laboratory mouse has been well developed and generated more and more mouse lines for biomedical research. To advance our science exploration, it is necessary to share genetically modified mouse lines with collaborators between institutions, even in different countries. The transfer process is complicated. Significant...

The locus coeruleus (LC) is an important brainstem area involved in cocaine addiction. However, evidence to elucidate how cocaine modulates the activity of LC neurons remains incomplete. Here, we performed whole recordings in brain slices to evaluate the effects of cocaine on the sodium (Na(+)), potassium (K(+)), calcium (Ca(2+)) channels, and glut...

Neurotransmitter release from presynaptic cells can be recorded by postsynaptic potentials/currents in central nerve system. However, little is known about how to record nerve release in cardiovascular system in fresh tissue or in vivo. We have developed two novel methods for recording catecholamine release induced by nerve action potentials in car...

Bis(monoacylglycero)phosphate (BMP) is an unusually shaped, negatively charged phospholipid found in elevated concentrations in the late endosomes. The unusual structure and stereochemistry of BMP are thought to play important roles in the endosome, including structural integrity, endosome maturation, and lipid/protein sorting and trafficking. We h...