Experimental Neurobiology最新文献_第10页

Low-voltage Activating K⁺ Channels in Cochlear Afferent Nerve Fiber Dendrites. 低电压激活耳蜗传入神经纤维树突中的K+通道。

IF 2.4 4区医学

Experimental Neurobiology Pub Date : 2022-08-31 DOI: 10.5607/en22013

Kushal Sharma, Kwon Woo Kang, Young-Woo Seo, Elisabeth Glowatzki, Eunyoung Yi

{"title":"Low-voltage Activating K+ Channels in Cochlear Afferent Nerve Fiber Dendrites.","authors":"Kushal Sharma, Kwon Woo Kang, Young-Woo Seo, Elisabeth Glowatzki, Eunyoung Yi","doi":"10.5607/en22013","DOIUrl":"https://doi.org/10.5607/en22013","url":null,"abstract":"Cochlear afferent nerve fibers (ANF) are the first neurons in the ascending auditory pathway. We investigated the low-voltage activating K+ channels expressed in ANF dendrites using isolated rat cochlear segments. Whole cell patch clamp recordings were made from the dendritic terminals of ANFs. Outward currents activating at membrane potentials as low as -64 mV were observed in all dendrites studied. These currents were inhibited by 4-aminopyridine (4-AP), a blocker known to preferentially inhibit low-voltage activating K+ currents (IKL) in CNS auditory neurons and spiral ganglion neurons. When the dendritic IKL was blocked by 4-AP, the EPSP decay time was significantly prolonged, suggesting that dendritic IKL speeds up the decay of EPSPs and likely modulates action potentials of ANFs. To reveal molecular subtype of dendritic IKL, α-dendrotoxin (α-DTX), a selective inhibitor for Kv1.1, Kv1.2, and Kv1.6 containing channels, was tested. α-DTX inhibited 23±9% of dendritic IKL. To identify the α-DTXsensitive and α-DTX-insensitive components of IKL, immunofluorescence labeling was performed. Strong Kv1.1- and Kv1.2-immunoreactivity was found at unmyelinated dendritic segments, nodes of Ranvier, and cell bodies of most ANFs. A small fraction of ANF dendrites showed Kv7.2- immunoreactivity. These data suggest that dendritic IKL is conducted through Kv1.1and Kv1.2 channels, with a minor contribution from Kv7.2 and other as yet unidentified channels.","PeriodicalId":12263,"journal":{"name":"Experimental Neurobiology","volume":"31 4","pages":"243-259"},"PeriodicalIF":2.4,"publicationDate":"2022-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/07/d4/en-31-4-243.PMC9471414.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40340902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

Simultaneous Cellular Imaging, Electrical Recording and Stimulation of Hippocampal Activity in Freely Behaving Mice. 自由行为小鼠海马活动的同步细胞成像、电记录和刺激。

IF 2.4 4区医学

Experimental Neurobiology Pub Date : 2022-06-30 DOI: 10.5607/en22011

Chae Young Kim, Sang Jeong Kim, Fabian Kloosterman

{"title":"Simultaneous Cellular Imaging, Electrical Recording and Stimulation of Hippocampal Activity in Freely Behaving Mice.","authors":"Chae Young Kim, Sang Jeong Kim, Fabian Kloosterman","doi":"10.5607/en22011","DOIUrl":"https://doi.org/10.5607/en22011","url":null,"abstract":"Hippocampal sharp-wave ripple activity (SWRs) and the associated replay of neural activity patterns are well-known for their role in memory consolidation. This activity has been studied using electrophysiological approaches, as high temporal resolution is required to recognize SWRs in the neuronal signals. However, it has been difficult to analyze the individual contribution of neurons to task-specific SWRs, because it is hard to track neurons across a long time with electrophysiological recording. In this study, we recorded local field potential (LFP) signals in the hippocampal CA1 of freely behaving mice and simultaneously imaged calcium signals in contralateral CA1 to leverage the advantages of both electrophysiological and imaging approaches. We manufactured a custom-designed microdrive array and targeted tetrodes to the left hippocampus CA1 for LFP recording and applied electrical stimulation in the ventral hippocampal commissure (VHC) for closed-loop disruption of SWRs. Neuronal population imaging in the right hippocampal CA1 was performed using a miniature fluorescent microscope (Miniscope) and a genetically encoded calcium indicator. As SWRs show highly synchronized bilateral occurrence, calcium signals of SWR-participating neurons could be identified and tracked in spontaneous or SWR-disrupted conditions. Using this approach, we identified a subpopulation of CA1 neurons showing synchronous calcium elevation to SWRs. Our results showed that SWR-related calcium transients are more disrupted by electrical stimulation than non-SWRrelated calcium transients, validating the capability of the system to detect and disrupt SWRs. Our dual recording method can be used to uncover the dynamic participation of individual neurons in SWRs and replay over extended time windows.","PeriodicalId":12263,"journal":{"name":"Experimental Neurobiology","volume":" ","pages":"208-220"},"PeriodicalIF":2.4,"publicationDate":"2022-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/bd/ea/en-31-3-208.PMC9272116.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40470371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cranial and Spinal Window Preparation for in vivo Optical Neuroimaging in Rodents and Related Experimental Techniques. 啮齿类动物体内光学神经成像的颅、脊窗制备及相关实验技术。

IF 2.4 4区医学

Experimental Neurobiology Pub Date : 2022-06-30 DOI: 10.5607/en22015

Chanmi Yeon, Jeong Myo Im, Minsung Kim, Young Ro Kim, Euiheon Chung

{"title":"Cranial and Spinal Window Preparation for in vivo Optical Neuroimaging in Rodents and Related Experimental Techniques.","authors":"Chanmi Yeon, Jeong Myo Im, Minsung Kim, Young Ro Kim, Euiheon Chung","doi":"10.5607/en22015","DOIUrl":"https://doi.org/10.5607/en22015","url":null,"abstract":"Optical neuroimaging provides an effective neuroscience tool for multi-scale investigation of the neural structures and functions, ranging from molecular, cellular activities to the inter-regional connectivity assessment. Amongst experimental preparations, the implementation of an artificial window to the central nervous system (CNS) is primarily required for optical visualization of the CNS and associated brain activities through the opaque skin and bone. Either thinning down or removing portions of the skull or spine is necessary for unobstructed long-term in vivo observations, for which types of the cranial and spinal window and applied materials vary depending on the study objectives. As diversely useful, a window can be designed to accommodate other experimental methods such as electrophysiology or optogenetics. Moreover, auxiliary apparatuses would allow the recording in synchrony with behavior of large-scale brain connectivity signals across the CNS, such as olfactory bulb, cerebral cortex, cerebellum, and spinal cord. Such advancements in the cranial and spinal window have resulted in a paradigm shift in neuroscience, enabling in vivo investigation of the brain function and dysfunction at the microscopic, cellular level. This Review addresses the types and classifications of windows used in optical neuroimaging while describing how to perform in vivo studies using rodent models in combination with other experimental modalities during behavioral tests. The cranial and spinal window has enabled longitudinal examination of evolving neural mechanisms via in situ visualization of the brain. We expect transformable and multi-functional cranial and spinal windows to become commonplace in neuroscience laboratories, further facilitating advances in optical neuroimaging systems.","PeriodicalId":12263,"journal":{"name":"Experimental Neurobiology","volume":" ","pages":"131-146"},"PeriodicalIF":2.4,"publicationDate":"2022-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/9b/a0/en-31-3-131.PMC9272117.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40469900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

The Change in Circadian Rhythms in P301S Transgenic Mice is Linked to Variability in Hsp70-related Tau Disaggregation. P301S转基因小鼠的昼夜节律变化与hsp70相关的Tau分解变异性有关。

IF 2.4 4区医学

Experimental Neurobiology Pub Date : 2022-06-30 DOI: 10.5607/en22019

Song Mi Han, Yu Jung Jang, Eun Young Kim, Sun Ah Park

{"title":"The Change in Circadian Rhythms in P301S Transgenic Mice is Linked to Variability in Hsp70-related Tau Disaggregation.","authors":"Song Mi Han, Yu Jung Jang, Eun Young Kim, Sun Ah Park","doi":"10.5607/en22019","DOIUrl":"https://doi.org/10.5607/en22019","url":null,"abstract":"Circadian disruption often involves a neurodegenerative disorder, such as Alzheimer's disease or frontotemporal dementia, which are characterized by intraneuronal tau accumulations. The altered sleep pattern and diurnal rhythms in these disorders are the results of tau pathology. The circadian disturbance in reverse is thought to develop and potentially aggravate the condition. However, the underlying mechanism is not fully understood. In this study, perturbed oscillations in BMAL1 , the core clock gene, were observed in P301S tau transgenic mice. Tau fractionation analysis of the hippocampus revealed profound fluctuations in soluble and insoluble tau protein levels that were in opposite directions to each other according to zeitgeber time. Interestingly, a diurnal oscillation was detected in the heat shock 70 kDa protein 1A (Hsp70) chaperone that was in-phase with soluble tau but out-of-phase with insoluble tau. Tau protein levels decreased in the soluble and insoluble fractions when Hsp70 was overexpressed in HEK293T cells. Transfection of the BMAL1 carrying vector was continual with the increase in Hsp70 expression and diminished tau protein levels, and it was effectively attenuated by the knockdown of Hsp70, suggesting that Bmal1 could modulate tau protein by Hsp70. Our results suggest that altered circadian oscillations affect tau status and solubility by modulating Hsp70 expression in an experimental model of tau pathology. These findings suggest Hsp70 as a possible pathogenic link between circadian disruption and aggravations of tau pathology.","PeriodicalId":12263,"journal":{"name":"Experimental Neurobiology","volume":" ","pages":"196-207"},"PeriodicalIF":2.4,"publicationDate":"2022-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/11/8c/en-31-3-196.PMC9272121.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40470370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

Unaltered Tonic Inhibition in the Arcuate Nucleus of Diet-induced Obese Mice. 饮食诱导肥胖小鼠弓形核不变的强直抑制。

IF 2.4 4区医学

Experimental Neurobiology Pub Date : 2022-06-30 DOI: 10.5607/en22014

Moonsun Sa, Jung Moo Lee, Mingu Gordon Park, Jiwoon Lim, Jong Min Joseph Kim, Wuhyun Koh, Bo-Eun Yoon, C Justin Lee

{"title":"Unaltered Tonic Inhibition in the Arcuate Nucleus of Diet-induced Obese Mice.","authors":"Moonsun Sa, Jung Moo Lee, Mingu Gordon Park, Jiwoon Lim, Jong Min Joseph Kim, Wuhyun Koh, Bo-Eun Yoon, C Justin Lee","doi":"10.5607/en22014","DOIUrl":"https://doi.org/10.5607/en22014","url":null,"abstract":"The principal inhibitory transmitter, γ-aminobutyric acid (GABA), is critical for maintaining hypothalamic homeostasis and released from neurons phasically, as well as from astrocytes tonically. Although astrocytes in the arcuate nucleus (ARC) of the hypothalamus are shown to transform into reactive astrocytes, the tonic inhibition by astrocytic GABA has not been adequately investigated in diet-induced obesity (DIO). Here, we investigated the expression of monoamine oxidase-B (MAOB), a GABA-synthesizing enzyme, in reactive astrocytes in obese mice. We observed that a chronic high-fat diet (HFD) significantly increased astrocytic MAOB and cellular GABA content, along with enhanced hypertrophy of astrocytes in the ARC. Unexpectedly, we found that the level of tonic GABA was unaltered in chronic HFD mice using whole-cell patch-clamp recordings in the ARC. Furthermore, the GABA-induced current was increased with elevated GABAA receptor α5 (GABRA5) expression. Surprisingly, we found that a nonselective GABA transporter (GAT) inhibitor, nipecotic acid (NPA)-induced current was significantly increased in chronic HFD mice. We observed that GAT1 inhibitor, NO711-induced current was significantly increased, whereas GAT3 inhibitor, SNAP5114-induced current was not altered. The unexpected unaltered tonic inhibition was due to an increase of GABA clearance in the ARC by neuronal GAT1 rather than astrocytic GAT3. These results imply that increased astrocytic GABA synthesis and neuronal GABAA receptor were compensated by GABA clearance, resulting in unaltered tonic GABA inhibition in the ARC of the hypothalamus in obese mice. Taken together, GABA-related molecular pathways in the ARC dynamically regulate the tonic inhibition to maintain hypothalamic homeostasis against the HFD challenge.","PeriodicalId":12263,"journal":{"name":"Experimental Neurobiology","volume":"31 3","pages":"147-157"},"PeriodicalIF":2.4,"publicationDate":"2022-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/4c/85/en-31-3-147.PMC9272119.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10325817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

Astrocyte-targeted Overproduction of IL-10 Reduces Neurodegeneration after TBI. 星形胶质细胞靶向IL-10的过量产生减少TBI后神经退行性变。

IF 2.4 4区医学

Experimental Neurobiology Pub Date : 2022-06-30 DOI: 10.5607/en21035

Mahsa Shanaki-Barvasad, Beatriz Almolda, Berta González, Bernardo Castellano

{"title":"Astrocyte-targeted Overproduction of IL-10 Reduces Neurodegeneration after TBI.","authors":"Mahsa Shanaki-Barvasad, Beatriz Almolda, Berta González, Bernardo Castellano","doi":"10.5607/en21035","DOIUrl":"https://doi.org/10.5607/en21035","url":null,"abstract":"Traumatic brain injury is the greatest cause of disability and death in young adults in the developed world. The outcome for a TBI patient is determined by the severity of the injury, not only from the initial insult but, especially, as a product of the secondary injury. It is proposed that this secondary injury is directly linked to neuro-inflammation, with the production of pro-inflammatory mediators, activation of resident glial cells and infiltration of peripheral immune cells. In this context, anti-inflammatory treatments are one of the most promising therapies to dampen the inflammatory response associated with TBI and to reduce secondary injury. In this sense, the main objective of the present study is to elucidate the effect of local production of IL-10 in the neurological outcome after TBI. For this purpose, a cryogenic lesion was caused in transgenic animals overproducing IL-10 under the GFAP promoter on astrocytes (GFAP-IL10Tg mice) and the neuro-protection, microglial activation and leukocyte recruitment were evaluated. Our results showed a protective effect of IL-10 on neurons at early time-points after TBI, in correlation with a shift in the microglial activation profile towards a down-regulating phenotype and lower production of pro-inflammatory cytokines. Concomitantly, we observed a reduction in the BBB leakage together with modifications in leukocyte infiltration into the affected area. In conclusion, local IL-10 production modifies the neuro-inflammatory response after TBI, shifting it to anti-inflammatory and neuro-protective conditions. These results point to IL-10 as a promising candidate to improve neuro-inflammation associated with TBI.","PeriodicalId":12263,"journal":{"name":"Experimental Neurobiology","volume":"31 3","pages":"173-195"},"PeriodicalIF":2.4,"publicationDate":"2022-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/d8/d5/en-31-3-173.PMC9272120.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10620555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 5

Time Course of Remote Neuropathology Following Diffuse Traumatic Brain Injury in the Male Rat. 雄性大鼠弥漫性创伤性脑损伤后远端神经病理的时间过程。

IF 2.4 4区医学

Experimental Neurobiology Pub Date : 2022-04-30 DOI: 10.5607/en21027

Katherine R Giordano, L Matthew Law, Jordan Henderson, Rachel K Rowe, Jonathan Lifshitz

{"title":"Time Course of Remote Neuropathology Following Diffuse Traumatic Brain Injury in the Male Rat.","authors":"Katherine R Giordano, L Matthew Law, Jordan Henderson, Rachel K Rowe, Jonathan Lifshitz","doi":"10.5607/en21027","DOIUrl":"https://doi.org/10.5607/en21027","url":null,"abstract":"Traumatic brain injury (TBI) can affect different regions throughout the brain. Regions near the site of impact are the most vulnerable to injury. However, damage to distal regions occurs. We investigated progressive neuropathology in the dorsal hippocampus (near the impact) and cerebellum (distal to the impact) after diffuse TBI. Adult male rats were subjected to midline fluid percussion injury or sham injury. Brain tissue was stained by the amino cupric silver stain. Neuropathology was quantified in sub-regions of the dorsal hippocampus at 1, 7, and 28 days post-injury (DPI) and coronal cerebellar sections at 1, 2, and 7 DPI. The highest observed neuropathology in the dentate gyrus occurred at 7 DPI which attenuated by 28 DPI, whereas the highest observed neuropathology was at 1 DPI in the CA3 region. There was no significant neuropathology in the CA1 region at any time point. Neuropathology was increased at 7 DPI in the cerebellum compared to shams and stripes of pathology were observed in the molecular layer perpendicular to the cerebellar cortical surface. Together these data show that diffuse TBI can result in neuropathology across the brain. By describing the time course of pathology in response to TBI, it is possible to build the temporal profile of disease progression.","PeriodicalId":12263,"journal":{"name":"Experimental Neurobiology","volume":"31 2","pages":"105-115"},"PeriodicalIF":2.4,"publicationDate":"2022-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/00/5a/en-31-2-105.PMC9194637.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9587839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

Neonatal Mice Spinal Cord Interneurons Send Axons through the Dorsal Roots 新生小鼠脊髓中间神经元通过背根发送轴突

IF 2.4 4区医学

Experimental Neurobiology Pub Date : 2022-04-30 DOI: 10.5607/en21019

L. P. Osuna-Carrasco, S. Dueñas-Jiménez, Carmen Toro-Castillo, Braniff De la Torre, I. Aguilar-García, Jonatan Alpirez, Luis Castillo, J. M. Dueñas-Jiménez

{"title":"Neonatal Mice Spinal Cord Interneurons Send Axons through the Dorsal Roots","authors":"L. P. Osuna-Carrasco, S. Dueñas-Jiménez, Carmen Toro-Castillo, Braniff De la Torre, I. Aguilar-García, Jonatan Alpirez, Luis Castillo, J. M. Dueñas-Jiménez","doi":"10.5607/en21019","DOIUrl":"https://doi.org/10.5607/en21019","url":null,"abstract":"Spontaneous interneuron activity plays a critical role in developing neuronal networks. Discharges conducted antidromically along the dorsal root (DR) precede those from the ventral root’s (VR) motoneurons. This work studied whether spinal interneurons project axons into the neonate’s dorsal roots. Experiments were carried out in postnatal Swiss-Webster mice. We utilized a staining technique and found that interneurons in the spinal cord’s dorsal horn send axons through the dorsal roots. In vitro electrophysiological recordings showed antidromic action potentials (dorsal root reflex; DRR) produced by depolarizing the primary afferent terminals. These reflexes appeared by stimulating the adjacent dorsal roots. We found that bicuculline reduced the DRR evoked by L5 dorsal root stimulation when recording from the L4 dorsal root. Simultaneously, the monosynaptic reflex (MR) in the L5 ventral root was not affected; nevertheless, a long-lasting after-discharge appeared. The addition of 2-amino-5 phosphonovaleric acid (AP5), an NMDA receptor antagonist, abolished the MR without changing the after-discharge. The absence of DRR and MR facilitated single action potentials in the dorsal and ventral roots that persisted even in low Ca2+ concentrations. The results suggest that firing interneurons could send their axons through the dorsal roots. These interneurons could activate motoneurons producing individual spikes recorded in the ventral roots. Identifying these interneurons and the persistence of their neuronal connectivity in adulthood remains to be established.","PeriodicalId":12263,"journal":{"name":"Experimental Neurobiology","volume":"31 1","pages":"89 - 96"},"PeriodicalIF":2.4,"publicationDate":"2022-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43897836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Physiological Roles of Monomeric Amyloid-β and Implications for Alzheimer's Disease Therapeutics. 单体淀粉样蛋白-β的生理作用及其对阿尔茨海默氏症治疗的意义

IF 1.8 4区医学

Experimental Neurobiology Pub Date : 2022-04-30 DOI: 10.5607/en22004

Hyomin Jeong, Heewon Shin, Seungpyo Hong, YoungSoo Kim

{"title":"Physiological Roles of Monomeric Amyloid-β and Implications for Alzheimer's Disease Therapeutics.","authors":"Hyomin Jeong, Heewon Shin, Seungpyo Hong, YoungSoo Kim","doi":"10.5607/en22004","DOIUrl":"10.5607/en22004","url":null,"abstract":"Alzheimer's disease (AD) progressively inflicts impairment of synaptic functions with notable deposition of amyloid-β (Aβ) as senile plaques within the extracellular space of the brain. Accordingly, therapeutic directions for AD have focused on clearing Aβ plaques or preventing amyloidogenesis based on the amyloid cascade hypothesis. However, the emerging evidence suggests that Aβ serves biological roles, which include suppressing microbial infections, regulating synaptic plasticity, promoting recovery after brain injury, sealing leaks in the blood-brain barrier, and possibly inhibiting the proliferation of cancer cells. More importantly, these functions were found in in vitro and in vivo investigations in a hormetic manner, that is to be neuroprotective at low concentrations and pathological at high concentrations. We herein summarize the physiological roles of monomeric Aβ and current Aβ-directed therapies in clinical trials. Based on the evidence, we propose that novel therapeutics targeting Aβ should selectively target Aβ in neurotoxic forms such as oligomers while retaining monomeric Aβ in order to preserve the physiological functions of Aβ monomers.","PeriodicalId":12263,"journal":{"name":"Experimental Neurobiology","volume":"31 2","pages":"65-88"},"PeriodicalIF":1.8,"publicationDate":"2022-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/fd/b3/en-31-2-65.PMC9194638.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10252253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Deletion of Phospholipase C β1 in the Thalamic Reticular Nucleus Induces Absence Seizures 丘脑网状核中磷脂酶C β1缺失诱导癫痫发作

IF 2.4 4区医学

Experimental Neurobiology Pub Date : 2022-04-30 DOI: 10.5607/en22007

Bomi Chang, Junweon Byun, Ko Keun Kim, Seung Eun Lee, Boyoung Lee, Key‐Sun Kim, Hoon Ryu, Hee-Sup Shin, Eunji Cheong

{"title":"Deletion of Phospholipase C β1 in the Thalamic Reticular Nucleus Induces Absence Seizures","authors":"Bomi Chang, Junweon Byun, Ko Keun Kim, Seung Eun Lee, Boyoung Lee, Key‐Sun Kim, Hoon Ryu, Hee-Sup Shin, Eunji Cheong","doi":"10.5607/en22007","DOIUrl":"https://doi.org/10.5607/en22007","url":null,"abstract":"Absence seizures are caused by abnormal synchronized oscillations in the thalamocortical (TC) circuit, which result in widespread spike-and-wave discharges (SWDs) on electroencephalography (EEG) as well as impairment of consciousness. Thalamic reticular nucleus (TRN) and TC neurons are known to interact dynamically to generate TC circuitry oscillations during SWDs. Clinical studies have suggested the association of Plcβ1 with early-onset epilepsy, including absence seizures. However, the brain regions and circuit mechanisms related to the generation of absence seizures with Plcβ1 deficiency are unknown. In this study, we found that loss of Plcβ1 in mice caused spontaneous complex-type seizures, including convulsive and absence seizures. Importantly, TRN-specific deletion of Plcβ1 led to the development of only spontaneous SWDs, and no other types of seizures were observed. Ex vivo slice patch recording demonstrated that the number of spikes, an intrinsic TRN neuronal property, was significantly reduced in both tonic and burst firing modes in the absence of Plcβ1. We conclude that the loss of Plcβ1 in the TRN leads to decreased excitability and impairs normal inhibitory neuronal function, thereby disrupting feedforward inhibition of the TC circuitry, which is sufficient to cause hypersynchrony of the TC system and eventually leads to spontaneous absence seizures. Our study not only provides a novel mechanism for the induction of SWDs in Plcβ1-deficient patients but also offers guidance for the development of diagnostic and therapeutic tools for absence epilepsy.","PeriodicalId":12263,"journal":{"name":"Experimental Neurobiology","volume":"31 1","pages":"116 - 130"},"PeriodicalIF":2.4,"publicationDate":"2022-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44629233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0