Biology subjects

Han, Y.-E.

Publications and source records attributed to Han, Y.-E..

4 recordsLinked to original sources

bioRxiv2023

Discrete projections from MCH neurons mediate anti-parkinsonian effects of acupuncture

Parkinsons disease (PD) presents with typical motor dysfunction and non-motor symptoms, including memory loss. Although acupuncture is suggested as an alternative therapy for PD, its neuroanatomical mechanisms remain unclear. We demonstrate that acupuncture ameliorates both motor and memory deficits in PD mice through activation of melanin-concentrating hormone (MCH) neurons in the lateral hypothalamus and zona incerta (LH/ZI)--MCHLH/ZI-- via nerve conduction. We identify two distinct subpopulations of MCHLH/ZI projecting to the substantia nigra and hippocampus, each of which is responsible for controlling motor and memory function. This effect can be attributed to MCH-mediated recovery from dopaminergic neurodegeneration, reactive gliosis, and impaired hippocampal synaptic plasticity. Collectively, MCHLH/ZI constitutes not only the neuroanatomical basis of acupuncture but also a potential cellular target for treating both motor and non-motor PD symptoms. One-Sentence SummaryAcupuncture alleviates both motor and non-motor symptoms in Parkinsons disease by activating two distinct MCH projections.

neuroscience↗

bioRxiv2022

Characterization of TMEM43 as a novel ion channel

The TMEM43 gene has been reported to play supportive but critical roles in human diseases including cancer, arrhythmogenic right ventricular cardiomyopathy (ARVC), and auditory neuropathy spectrum disorder (ANSD). However, direct characterization of the TMEM43 protein itself and its role in the brain remain unexplored. In this study, we demonstrated that TMEM43 confers ion channel activities via the lipid bilayer reconstitution of purified TMEM43 protein and further characterized TMEM43 as a pH-sensing cation channel in the heterologous expression system. TMEM43 was shown to conduct transjunctional potentials between adjacent cells, further facilitating electrical couplings of the gap junctions. In the hippocampus of TMEM43 knockout (KO) mice, we observed a decrease in astrocytic dye diffusion and potassium buffering, an increase in neuronal excitability, and alterations in AMPA/NMDA ratio and LTP. The electrophysiological changes in the KO mice led to a disturbance in memory retrieval which was rescued with TMEM43 overexpression. These results indicate that TMEM43 actively participates in gap junction networks of the hippocampus to prevent neurons from hyperexcitability, which is critical for memory retrieval. Together, our study elucidates the molecular and functional identities of TMEM43 and underscores its role in memory retrieval.

molecular biology↗

bioRxiv2022

High-order thalamic and motor cortex inputs integrate sublinearly into tuft dendrites of pyramidal neurons in mouse somatosensory cortex

Tuft dendrites of pyramidal neurons housed in layer 1 of the neocortex form extensive excitatory synaptic connections with long-range cortical and high-order thalamic axons, along with diverse inhibitory inputs. Recently, we reported that synapses from the vibrissal primary motor cortex (vM1) and posterior medial thalamic nucleus (POm) are spatially clustered together in the same set of distal dendrites, suggesting a close functional interaction. In this study, we evaluated how these two types of synapses interact with each other using in vivo two-photon Ca2+ imaging and electrophysiology. We observed that dendritic Ca2+ responses could be efficiently evoked by electrical stimulation of POm or vM1 in the overlapping set of dendritic branches, rejecting the idea of branch-wise origin-selective synaptic wiring. Surprisingly, the Ca2+ responses upon coincident POm and vM1 stimulation summed sublinearly. We attribute this sublinearity to mutual inhibition via inhibitory neurons because synaptic currents generated by POm and vM1 also integrated sublinearly, but pharmacologically isolated direct synaptic currents summed linearly. Inhibitory neurons receiving POm inputs in the superficial cortical layer negatively regulated vM1-evoked responses. Finally, POm and vM1 innervated overlapping but distinct populations of somatostatin-expressing inhibitory neurons. Thus, POm and vM1 inputs negatively modulate each other in the mouse somatosensory cortex.

neuroscience↗

bioRxiv2021

Visualization of reactive astrocytes in living brain of Alzheimer's disease patient

An early appearance of reactive astrocytes is a hallmark of Alzheimers disease (AD)1,2, providing a substrate for early diagnostic neuroimaging targets. However, there is no clinically validated neuroimaging probe to visualize the reactive astrogliosis in the human brain in vivo. Here, we report that PET/CT imaging with 11C-acetate and 18F-fluorodeoxyglucose (18F-FDG) functionally visualizes the reactive astrocyte-mediated neuronal hypometabolism in the brains with neuroinflammation and AD. We demonstrate that reactive astrocytes excessively absorb acetate through elevated monocarboxylate transporter-1 (MCT1), leading to aberrant GABA synthesis and release which suppresses neuronal glucose uptake through decreased glucose transporter-3 (GLUT3) in both animal and human brains. We propose the non-invasive functional PET/CT imaging for astrocytic acetate-hypermetabolism and neuronal glucose-hypometabolism as an advanced diagnostic strategy for early stages of AD.

neuroscience↗