Effects of intraventricular transplantation of NGF-secreting cells on cholinergic basal forebrain neurons after partial immunolesion

S. Roßner, J. Yu, D. Pizzo, K. Werrbach-Perez, R. Schliebs, V. Bigl, J. R. Perez-Polo

    Research output: Contribution to journalArticle

    42 Citations (Scopus)

    Abstract

    The aim of the present study was to examine the effects of nerve growth factor on brain cholinergic function after a partial immunolesion to the rat cholinergic basal forebrain neurons (CBFNs) by 192 IgG-saporin. Two weeks after intraventricular injections of 1.3 μg of 192 IgG-saporin, about 50% of CBFNs were lost which was associated with 40-60% reductions of choline acetyltransferase (ChAT) and high-affinity choline uptake (HACU) activities throughout the basal forebrain cholinergic system. Two groups of lesioned animals received intraventricular transplantations of mouse 3T3 fibroblasts retrovirally transfected with either the rat NGF gene (3T3(NGF+)) or the retrovirus alone (3T3(NGF-)) and were sacrificed eight weeks later. In vivo production of NGF by 3T3(NGF+) cells was confirmed by NGF immunohistochemistry on the grafts and NGF immunoassay on cerebrospinal fluid (CSF) samples. Both ChAT and HACU activities returned to normal control levels in the basal forebrain and cortex after 3T3(NGF+) transplants, whereas no recovery was observed in 3T3(NGF-) transplanted animals. There was a 25% increase in the size of remaining CBFNs and an increased staining intensity for NGF immunoreactivity in these cells after NGF treatments. Acetylcholinesterase (AChE) histochemistry revealed that the optical density of AChE-positive fibers in the cerebral cortex and hippocampus were reduced by about 60% in immunolesioned rats which were completely restored by 3T3(NGF+) grafts. In addition, decreases in growth-associated protein (GAP)- 43 immunoreactivity after immunolesion and increases in synaptophysin immunoreactivity after 3T3(NGF+) grafts were observed in the hippocampus. Our results further confirm the notion that transfected NGF-secreting cells are useful in long-term in vivo NGF treatment and NGF can up-regulate CBFN function. They also highly suggest that NGF induces terminal sprouting from remaining CBFNs.

    Original languageEnglish (US)
    Pages (from-to)40-56
    Number of pages17
    JournalJournal of Neuroscience Research
    Volume45
    Issue number1
    DOIs
    StatePublished - 1996

    Fingerprint

    Nerve Growth Factor
    Cholinergic Agents
    Transplantation
    Neurons
    Transplants
    Basal Forebrain
    Choline O-Acetyltransferase
    Acetylcholinesterase
    Choline
    Hippocampus
    Intraventricular Injections
    GAP-43 Protein
    3T3 Cells
    Synaptophysin
    Retroviridae
    Immunoassay

    Keywords

    • AChE
    • ChAT
    • high-affinity choline uptake
    • p75(NFGR)
    • sprouting

    ASJC Scopus subject areas

    • Neuroscience(all)

    Cite this

    Effects of intraventricular transplantation of NGF-secreting cells on cholinergic basal forebrain neurons after partial immunolesion. / Roßner, S.; Yu, J.; Pizzo, D.; Werrbach-Perez, K.; Schliebs, R.; Bigl, V.; Perez-Polo, J. R.

    In: Journal of Neuroscience Research, Vol. 45, No. 1, 1996, p. 40-56.

    Research output: Contribution to journalArticle

    Roßner, S. ; Yu, J. ; Pizzo, D. ; Werrbach-Perez, K. ; Schliebs, R. ; Bigl, V. ; Perez-Polo, J. R. / Effects of intraventricular transplantation of NGF-secreting cells on cholinergic basal forebrain neurons after partial immunolesion. In: Journal of Neuroscience Research. 1996 ; Vol. 45, No. 1. pp. 40-56.
    @article{c7aafc76224846d290927b4aea01d770,
    title = "Effects of intraventricular transplantation of NGF-secreting cells on cholinergic basal forebrain neurons after partial immunolesion",
    abstract = "The aim of the present study was to examine the effects of nerve growth factor on brain cholinergic function after a partial immunolesion to the rat cholinergic basal forebrain neurons (CBFNs) by 192 IgG-saporin. Two weeks after intraventricular injections of 1.3 μg of 192 IgG-saporin, about 50{\%} of CBFNs were lost which was associated with 40-60{\%} reductions of choline acetyltransferase (ChAT) and high-affinity choline uptake (HACU) activities throughout the basal forebrain cholinergic system. Two groups of lesioned animals received intraventricular transplantations of mouse 3T3 fibroblasts retrovirally transfected with either the rat NGF gene (3T3(NGF+)) or the retrovirus alone (3T3(NGF-)) and were sacrificed eight weeks later. In vivo production of NGF by 3T3(NGF+) cells was confirmed by NGF immunohistochemistry on the grafts and NGF immunoassay on cerebrospinal fluid (CSF) samples. Both ChAT and HACU activities returned to normal control levels in the basal forebrain and cortex after 3T3(NGF+) transplants, whereas no recovery was observed in 3T3(NGF-) transplanted animals. There was a 25{\%} increase in the size of remaining CBFNs and an increased staining intensity for NGF immunoreactivity in these cells after NGF treatments. Acetylcholinesterase (AChE) histochemistry revealed that the optical density of AChE-positive fibers in the cerebral cortex and hippocampus were reduced by about 60{\%} in immunolesioned rats which were completely restored by 3T3(NGF+) grafts. In addition, decreases in growth-associated protein (GAP)- 43 immunoreactivity after immunolesion and increases in synaptophysin immunoreactivity after 3T3(NGF+) grafts were observed in the hippocampus. Our results further confirm the notion that transfected NGF-secreting cells are useful in long-term in vivo NGF treatment and NGF can up-regulate CBFN function. They also highly suggest that NGF induces terminal sprouting from remaining CBFNs.",
    keywords = "AChE, ChAT, high-affinity choline uptake, p75(NFGR), sprouting",
    author = "S. Ro{\ss}ner and J. Yu and D. Pizzo and K. Werrbach-Perez and R. Schliebs and V. Bigl and Perez-Polo, {J. R.}",
    year = "1996",
    doi = "10.1002/(SICI)1097-4547(19960701)45:1<40::AID-JNR4>3.0.CO;2-H",
    language = "English (US)",
    volume = "45",
    pages = "40--56",
    journal = "Journal of Neuroscience Research",
    issn = "0360-4012",
    publisher = "Wiley-Liss Inc.",
    number = "1",

    }

    TY - JOUR

    T1 - Effects of intraventricular transplantation of NGF-secreting cells on cholinergic basal forebrain neurons after partial immunolesion

    AU - Roßner, S.

    AU - Yu, J.

    AU - Pizzo, D.

    AU - Werrbach-Perez, K.

    AU - Schliebs, R.

    AU - Bigl, V.

    AU - Perez-Polo, J. R.

    PY - 1996

    Y1 - 1996

    N2 - The aim of the present study was to examine the effects of nerve growth factor on brain cholinergic function after a partial immunolesion to the rat cholinergic basal forebrain neurons (CBFNs) by 192 IgG-saporin. Two weeks after intraventricular injections of 1.3 μg of 192 IgG-saporin, about 50% of CBFNs were lost which was associated with 40-60% reductions of choline acetyltransferase (ChAT) and high-affinity choline uptake (HACU) activities throughout the basal forebrain cholinergic system. Two groups of lesioned animals received intraventricular transplantations of mouse 3T3 fibroblasts retrovirally transfected with either the rat NGF gene (3T3(NGF+)) or the retrovirus alone (3T3(NGF-)) and were sacrificed eight weeks later. In vivo production of NGF by 3T3(NGF+) cells was confirmed by NGF immunohistochemistry on the grafts and NGF immunoassay on cerebrospinal fluid (CSF) samples. Both ChAT and HACU activities returned to normal control levels in the basal forebrain and cortex after 3T3(NGF+) transplants, whereas no recovery was observed in 3T3(NGF-) transplanted animals. There was a 25% increase in the size of remaining CBFNs and an increased staining intensity for NGF immunoreactivity in these cells after NGF treatments. Acetylcholinesterase (AChE) histochemistry revealed that the optical density of AChE-positive fibers in the cerebral cortex and hippocampus were reduced by about 60% in immunolesioned rats which were completely restored by 3T3(NGF+) grafts. In addition, decreases in growth-associated protein (GAP)- 43 immunoreactivity after immunolesion and increases in synaptophysin immunoreactivity after 3T3(NGF+) grafts were observed in the hippocampus. Our results further confirm the notion that transfected NGF-secreting cells are useful in long-term in vivo NGF treatment and NGF can up-regulate CBFN function. They also highly suggest that NGF induces terminal sprouting from remaining CBFNs.

    AB - The aim of the present study was to examine the effects of nerve growth factor on brain cholinergic function after a partial immunolesion to the rat cholinergic basal forebrain neurons (CBFNs) by 192 IgG-saporin. Two weeks after intraventricular injections of 1.3 μg of 192 IgG-saporin, about 50% of CBFNs were lost which was associated with 40-60% reductions of choline acetyltransferase (ChAT) and high-affinity choline uptake (HACU) activities throughout the basal forebrain cholinergic system. Two groups of lesioned animals received intraventricular transplantations of mouse 3T3 fibroblasts retrovirally transfected with either the rat NGF gene (3T3(NGF+)) or the retrovirus alone (3T3(NGF-)) and were sacrificed eight weeks later. In vivo production of NGF by 3T3(NGF+) cells was confirmed by NGF immunohistochemistry on the grafts and NGF immunoassay on cerebrospinal fluid (CSF) samples. Both ChAT and HACU activities returned to normal control levels in the basal forebrain and cortex after 3T3(NGF+) transplants, whereas no recovery was observed in 3T3(NGF-) transplanted animals. There was a 25% increase in the size of remaining CBFNs and an increased staining intensity for NGF immunoreactivity in these cells after NGF treatments. Acetylcholinesterase (AChE) histochemistry revealed that the optical density of AChE-positive fibers in the cerebral cortex and hippocampus were reduced by about 60% in immunolesioned rats which were completely restored by 3T3(NGF+) grafts. In addition, decreases in growth-associated protein (GAP)- 43 immunoreactivity after immunolesion and increases in synaptophysin immunoreactivity after 3T3(NGF+) grafts were observed in the hippocampus. Our results further confirm the notion that transfected NGF-secreting cells are useful in long-term in vivo NGF treatment and NGF can up-regulate CBFN function. They also highly suggest that NGF induces terminal sprouting from remaining CBFNs.

    KW - AChE

    KW - ChAT

    KW - high-affinity choline uptake

    KW - p75(NFGR)

    KW - sprouting

    UR - http://www.scopus.com/inward/record.url?scp=0029957824&partnerID=8YFLogxK

    UR - http://www.scopus.com/inward/citedby.url?scp=0029957824&partnerID=8YFLogxK

    U2 - 10.1002/(SICI)1097-4547(19960701)45:1<40::AID-JNR4>3.0.CO;2-H

    DO - 10.1002/(SICI)1097-4547(19960701)45:1<40::AID-JNR4>3.0.CO;2-H

    M3 - Article

    VL - 45

    SP - 40

    EP - 56

    JO - Journal of Neuroscience Research

    JF - Journal of Neuroscience Research

    SN - 0360-4012

    IS - 1

    ER -