Vesicular acetylcholine transporter in the basal forebrain improves cognitive impairment in chronic cerebral hypoperfusion rats by modulating theta oscillations in the hippocampus
Copyright © 2023 Elsevier B.V. All rights reserved..
The cholinergic transmission in the medial septum and ventral limb of the diagonal band of broca (MS/VDB)-hippocampal circuit and its associated theta oscillations play a crucial role in chronic cerebral hypoperfusion (CCH)-related cognitive impairment. However, the contribution and mechanism of the vesicular acetylcholine transporter (VAChT), a vital protein that regulates acetylcholine (ACh) release, in CCH-related cognitive impairment are not well understood. To investigate this, we established a rat model of CCH by performing 2-vessel occlusion (2-VO) and overexpressed VAChT in the MS/VDB via stereotaxic injection of adeno-associated virus (AAV). We evaluated the cognitive function of the rats using the Morris Water Maze (MWM) and Novel Object Recognition Test (NOR). We employed enzyme-linked immunosorbent assay (ELISA), Western blot (WB), and immunohistochemistry (IHC) to assess hippocampal cholinergic levels. We also conducted in vivo local field potentials (LFPs) recording experiments to evaluate changes in hippocampal theta oscillations and synchrony. Our findings showed that VAChT overexpression shortened the escape latency in the hidden platform test, increased swimming time in the platform quadrant in probe trains, and increased the recognition index (RI) in NOR. Moreover, VAChT overexpression increased hippocampal cholinergic levels, improved theta oscillations, and improved the synchrony of theta oscillations between CA1 and CA3 in CCH rats. These results suggest that VAChT plays a protective role in CCH-induced cognitive deficits by regulating cholinergic transmission in the MS/VDB-hippocampal circuit and promoting hippocampal theta oscillations. Therefore, VAChT could be a promising therapeutic target for treating CCH-related cognitive impairments.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2023 |
|---|---|
| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:807 |
|---|---|
| Enthalten in: |
Neuroscience letters - 807(2023) vom: 11. Juni, Seite 137281 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Zheng, Jiaxin [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 10.05.2023 Date Revised 18.05.2023 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1016/j.neulet.2023.137281 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM356234010 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM356234010 | ||
| 003 | DE-627 | ||
| 005 | 20231226070031.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.neulet.2023.137281 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1187.xml |
| 035 | |a (DE-627)NLM356234010 | ||
| 035 | |a (NLM)37120008 | ||
| 035 | |a (PII)S0304-3940(23)00240-9 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Zheng, Jiaxin |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Vesicular acetylcholine transporter in the basal forebrain improves cognitive impairment in chronic cerebral hypoperfusion rats by modulating theta oscillations in the hippocampus |
| 264 | 1 | |c 2023 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 10.05.2023 | ||
| 500 | |a Date Revised 18.05.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2023 Elsevier B.V. All rights reserved. | ||
| 520 | |a The cholinergic transmission in the medial septum and ventral limb of the diagonal band of broca (MS/VDB)-hippocampal circuit and its associated theta oscillations play a crucial role in chronic cerebral hypoperfusion (CCH)-related cognitive impairment. However, the contribution and mechanism of the vesicular acetylcholine transporter (VAChT), a vital protein that regulates acetylcholine (ACh) release, in CCH-related cognitive impairment are not well understood. To investigate this, we established a rat model of CCH by performing 2-vessel occlusion (2-VO) and overexpressed VAChT in the MS/VDB via stereotaxic injection of adeno-associated virus (AAV). We evaluated the cognitive function of the rats using the Morris Water Maze (MWM) and Novel Object Recognition Test (NOR). We employed enzyme-linked immunosorbent assay (ELISA), Western blot (WB), and immunohistochemistry (IHC) to assess hippocampal cholinergic levels. We also conducted in vivo local field potentials (LFPs) recording experiments to evaluate changes in hippocampal theta oscillations and synchrony. Our findings showed that VAChT overexpression shortened the escape latency in the hidden platform test, increased swimming time in the platform quadrant in probe trains, and increased the recognition index (RI) in NOR. Moreover, VAChT overexpression increased hippocampal cholinergic levels, improved theta oscillations, and improved the synchrony of theta oscillations between CA1 and CA3 in CCH rats. These results suggest that VAChT plays a protective role in CCH-induced cognitive deficits by regulating cholinergic transmission in the MS/VDB-hippocampal circuit and promoting hippocampal theta oscillations. Therefore, VAChT could be a promising therapeutic target for treating CCH-related cognitive impairments | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Chronic cerebral hypoperfusion | |
| 650 | 4 | |a Cognitive impairment | |
| 650 | 4 | |a Theta oscillations | |
| 650 | 4 | |a Vesicular acetylcholine transporter | |
| 650 | 7 | |a Vesicular Acetylcholine Transport Proteins |2 NLM | |
| 650 | 7 | |a Cholinergic Agents |2 NLM | |
| 700 | 1 | |a Zhu, Hong |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Zhenyu |e verfasserin |4 aut | |
| 700 | 1 | |a Du, Miaoyu |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Zhitian |e verfasserin |4 aut | |
| 700 | 1 | |a Lan, Liuyi |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Junjian |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Neuroscience letters |d 1975 |g 807(2023) vom: 11. Juni, Seite 137281 |w (DE-627)NLM000386529 |x 1872-7972 |7 nnns |
| 773 | 1 | 8 | |g volume:807 |g year:2023 |g day:11 |g month:06 |g pages:137281 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.neulet.2023.137281 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 807 |j 2023 |b 11 |c 06 |h 137281 | ||