| Title: |
GABAergic terminals are a source of Galanin to modulate cholinergic neuron development in the neonatal forebrain |
| Authors: |
Keimpema, Erik; Zheng, Kang; Barde, Swapnali Shantaram; Berghuis, Paul; Dobszay, Márton B.; Schnell, Robert; Mulder, Jan; Luiten, Paul G M; Xu, Zhiqing David; Runesson, Johan; Langel, Ülo; Lu, Bai; Hökfelt, Tomas; Harkany, Tibor |
| Source: |
Keimpema, E, Zheng, K, Barde, S S, Berghuis, P, Dobszay, M B, Schnell, R, Mulder, J, Luiten, P G M, Xu, Z D, Runesson, J, Langel, Ü, Lu, B, Hökfelt, T & Harkany, T 2014, 'GABAergic terminals are a source of Galanin to modulate cholinergic neuron development in the neonatal forebrain', Cerebral Cortex, vol. 24, no. 12, pp. 3277-3288. https://doi.org/10.1093/cercor/bht192 |
| Publication Year: |
2014 |
| Collection: |
University of Groningen research database |
| Subject Terms: |
Axon; Basal forebrain; Galanin receptor 2; Neurotrophin; Projection; NERVE GROWTH-FACTOR; ADULT SENSORY NEURONS; ROOT GANGLION-CELLS; ALZHEIMERS-DISEASE; NEURITE OUTGROWTH; LOCUS-COERULEUS; DIAGONAL BAND; RAT-BRAIN; NEUROTROPHIC FACTOR |
| Description: |
The distribution and (patho-)physiological role of neuropeptides in the adult and aging brain have been extensively studied. Galanin is an inhibitory neuropeptide that can coexist with ã-aminobutyric acid (GABA) in the adult forebrain. However, galanin's expression sites, mode of signaling, impact on neuronal morphology, and colocalization with amino acid neurotransmitters during brain development are less well understood. Here, we show that galaninergic innervation of cholinergic projection neurons, which preferentially express galanin receptor 2 (GalR2) in the neonatal mouse basal forebrain, develops by birth. Nerve growth factor (NGF), known to modulate cholinergic morphogenesis, increases GalR2 expression. GalR2 antagonism (M871) in neonates reduces the in vivo expression and axonal targeting of the vesicular acetylcholine transporter (VAChT), indispensable for cholinergic neurotransmission. During cholinergic neuritogenesis in vitro, GalR2 can recruit Rho-family GTPases to induce the extension of a VAChT-containing primary neurite, the prospective axon. In doing so, GalR2 signaling dose-dependently modulates directional filopodial growth and antagonizes NGF-induced growth cone differentiation. Galanin accumulates in GABA-containing nerve terminals in the neonatal basal forebrain, suggesting its contribution to activity-driven cholinergic development during the perinatal period. Overall, our data define the cellular specificity and molecular complexity of galanin action in the developing basal forebrain. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| ISSN: |
1047-3211; 1460-2199 |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/23897649; info:eu-repo/semantics/altIdentifier/wos/000345838300016; info:eu-repo/semantics/altIdentifier/hdl/https://hdl.handle.net/11370/bb3b59ac-1471-4555-91a2-f69e3466b713; info:eu-repo/semantics/altIdentifier/pissn/1047-3211; info:eu-repo/semantics/altIdentifier/eissn/1460-2199 |
| DOI: |
10.1093/cercor/bht192 |
| Availability: |
https://hdl.handle.net/11370/bb3b59ac-1471-4555-91a2-f69e3466b713; https://research.rug.nl/en/publications/bb3b59ac-1471-4555-91a2-f69e3466b713; https://doi.org/10.1093/cercor/bht192; https://pure.rug.nl/ws/files/62778381/GABAergic_Terminals_Are_a_Source_of_Galanin_to_Modulate_Cholinergic_Neuron_Development.pdf |
| Rights: |
info:eu-repo/semantics/openAccess ; https://www.rug.nl/library/open-access/article-25fa-pilot-end-user-agreement |
| Accession Number: |
edsbas.F4DD4DA6 |
| Database: |
BASE |