Cited by 251Nerve injury and regenerationNeurogenesis and neuroplasticity mechanismsNuclear Receptors and Signaling

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Brain-derived neurotrophic factor (BDNF) prevents the degeneration of medial septal cholinergic neurons following fimbria transection

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Morse, JK, Wiegand, SJ, Anderson, K, You, Y, Cai, N, Carnahan, J, Miller, J, DiStefano, PS, Altar, CA, Lindsay, RM·1993·The Journal of Neuroscience

DOI 10.1523/jneurosci.13-10-04146.1993PMC PMC6576390

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Abstract

Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, supports the survival of developing basal forebrain cholinergic neurons in vitro and is retrogradely transported by cholinergic neurons of the medial septum and diagonal band following intrahippocampal injections in vivo. To substantiate a potential role for BDNF in the maintenance of forebrain cholinergic neurons in the adult brain, we assessed the ability of BDNF to sustain the phenotype of medial septal cholinergic neurons following a unilateral transection of the fimbria. BDNF, NGF, or vehicle solutions were infused continuously in adult female rats either into the lateral ventricle (intracerebroventricularly) or directly into the septum for 2 weeks beginning at the time of the transection. In vehicle-infused animals, only 28% of the ChAT-immunoreactive neurons remained on the side ipsilateral to the lesion compared to the contralateral intact side. When infused intracerebroventricularly, both BDNF and NGF reduced the extent of the phenotypic loss, in that 44% and 68%, respectively, of the ChAT-immunopositive neurons remained on the lesioned side. Intraseptal infusion proved even more effective, in that following BDNF and NGF treatment 60% and 86%, respectively, of the normal complement of ChAT-immunopositive neurons were apparent on the side ipsilateral to the lesion. Similar results were obtained when an antibody to the low- affinity NGF receptor was used to identify the cholinergic neurons. To determine if the apparent greater efficacy of NGF compared to BDNF might be related to differences in delivery, we examined the patterns of distribution of radiolabeled BDNF and NGF injected into the lateral ventricle. 125I-BDNF showed only very little diffusion from the ventricles into the adjacent neural tissue and negligible retrograde labeling of the neurons within the basal forebrain. 125I-NGF, however, diffused readily into the brain, resulting in widespread retrograde labeling of basal forebrain neurons. A similarly limited distribution pattern was observed where BDNF was detected immunohistochemically in animals infused intracerebroventricularly (12 micrograms/d) for 2 weeks. In contrast, when delivered intraseptally, the same dose of BDNF exhibited a widespread diffusion within the surrounding neuropil and retrograde labeling of neurons in the medial septum and the vertical limb of the diagonal band. Thus, when delivered effectively, BDNF has a substantial capacity to rescue axotomized cholinergic neurons.

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Ip NY, Li Y, Yancopoulos GD, Lindsay RM (1993) Cultured hip- pocampal neurons show responses to BDNF, NT3, and NT4 but not NGF. J Neurosci, in press.

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Authors: Morse, J., Wiegand, S., Anderson, K., You, Y., Cai, N., Carnahan, J., Miller, J., DiStefano, P., Altar, C., & Lindsay, R.
Affiliations: Regeneron (United States) (US)
Venue: The Journal of Neuroscience
Publisher: Society for Neuroscience
Published: 1993-10-01
Volume: 13
Issue: 10
Pages: 4146-4156
ISSN: 0270-6474 (ISSN-L)
1529-2401
DOI: 10.1523/jneurosci.13-10-04146.1993
PMC: PMC6576390
OpenAlex: W1565095682
Cited by: 251
References: 47
Citations by year: 2026: 2 · 2025: 1 · 2023: 5 · 2022: 3 · 2021: 2 · 2020: 4 · 2019: 5 · 2018: 6 · 2017: 2 · 2016: 4 · 2015: 8 · 2014: 3 · 2013: 4 · 2012: 4
FWCI: 7.44
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by-nc-sa
creativecommons.org/licenses/by-nc-sa/4.0/ (vor, 182 d)
Locations: Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Receptors and Signaling
Keywords: brain-derived neurotrophic factor, neurotrophins, medial septum, cholinergic neurons, neurodegeneration, nerve growth factor, choline acetyltransferase, low-affinity NGF receptor, intracerebroventricular infusion, retrograde transport, basal forebrain, neuroprotection
MeSH terms: Animals, Brain, Cerebral Ventricles, Choline O-Acetyltransferase, Female, Humans, Injections, Intraventricular, Nerve Degeneration, Nerve Growth Factors, Nerve Tissue Proteins, Neurons, Recombinant Proteins, Prosencephalon, Rats, Sprague-Dawley, Receptors, Nerve Growth Factor, Brain-Derived Neurotrophic Factor, Rats

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Brain-derived neurotrophic factor (BDNF) prevents the degeneration of medial septal cholinergic neurons following fimbria transection

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