Long term changes in brain cholinergic markers and nerve growth factor levels after partial immunolesion

Zezong Gu, Juan Yu, J. Regino Perez-Polo

    Research output: Contribution to journalArticle

    15 Citations (Scopus)

    Abstract

    There are deficits in cholinergic basal forebrain neurons (CBFNs) in the aged brain and patients suffering Alzheimer's disease associated with a partial loss of the CBFNs. To mimic this partial loss and assess its long term effects on residual cholinergic activity and resultant target-derived nerve growth factor (NGF) levels, we produced a partial immunolesion to CBFNs with 192 IgG-saporin, an immunotoxin selectively taken up by p75(NTR)- bearing neurons. We measured two cholinergic markers, choline acetyltransferase (CHAT) and acetylcholinesterase (ACHE) activity, and NGF protein levels at 10 days, 1, 6 and 12 months postlesion. There were no significant changes in the cholinergic markers and the NGF protein levels in the sham-treated animal controls during the one year experiment. Ten days after 192 IgG-saporin treatment, ChAT activity decreased to 35-50% of controls in the olfactory bulb, hippocampus, and cortex. There was a minor but significant recovery of ChAT activity one year after the immunolesion in the hippocampus. Changes in ACHE activity mirrored the ChAT changes but were less robust. There were transient increases in NGF protein levels in the hippocampus and cortex that returned to basal levels at 6 months and 12 months postlesion, respectively. In summary, partial immunolesions resulted in partial region-specific and time-dependent recoveries of cholinergic activity in the target areas of the basal forebrain after a partial elimination of CBFNs and a return to basal levels of NGF protein consistent with the hypothesis that the remaining CBFNs compensated for losses of ChAT and NGF due to changes in cholinergic innervation of basal forebrain target areas.

    Original languageEnglish (US)
    Pages (from-to)190-197
    Number of pages8
    JournalBrain Research
    Volume801
    Issue number1-2
    DOIs
    StatePublished - Aug 10 1998

    Fingerprint

    Nerve Growth Factor
    Cholinergic Agents
    Brain
    Neurons
    Hippocampus
    Acetylcholinesterase
    Proteins
    Immunotoxins
    Choline O-Acetyltransferase
    Olfactory Bulb
    Basal Forebrain
    Alzheimer Disease

    Keywords

    • 192 IgG-saporin
    • Acetylcholinesterase
    • Choline acetyltransferase
    • Cholinergic basal forebrain neuron
    • Immunolesion
    • Nerve growth factor
    • Regeneration

    ASJC Scopus subject areas

    • Neuroscience(all)

    Cite this

    Long term changes in brain cholinergic markers and nerve growth factor levels after partial immunolesion. / Gu, Zezong; Yu, Juan; Perez-Polo, J. Regino.

    In: Brain Research, Vol. 801, No. 1-2, 10.08.1998, p. 190-197.

    Research output: Contribution to journalArticle

    Gu, Zezong ; Yu, Juan ; Perez-Polo, J. Regino. / Long term changes in brain cholinergic markers and nerve growth factor levels after partial immunolesion. In: Brain Research. 1998 ; Vol. 801, No. 1-2. pp. 190-197.
    @article{fcdba4ec147b4717aad1a5b806bbb5cf,
    title = "Long term changes in brain cholinergic markers and nerve growth factor levels after partial immunolesion",
    abstract = "There are deficits in cholinergic basal forebrain neurons (CBFNs) in the aged brain and patients suffering Alzheimer's disease associated with a partial loss of the CBFNs. To mimic this partial loss and assess its long term effects on residual cholinergic activity and resultant target-derived nerve growth factor (NGF) levels, we produced a partial immunolesion to CBFNs with 192 IgG-saporin, an immunotoxin selectively taken up by p75(NTR)- bearing neurons. We measured two cholinergic markers, choline acetyltransferase (CHAT) and acetylcholinesterase (ACHE) activity, and NGF protein levels at 10 days, 1, 6 and 12 months postlesion. There were no significant changes in the cholinergic markers and the NGF protein levels in the sham-treated animal controls during the one year experiment. Ten days after 192 IgG-saporin treatment, ChAT activity decreased to 35-50{\%} of controls in the olfactory bulb, hippocampus, and cortex. There was a minor but significant recovery of ChAT activity one year after the immunolesion in the hippocampus. Changes in ACHE activity mirrored the ChAT changes but were less robust. There were transient increases in NGF protein levels in the hippocampus and cortex that returned to basal levels at 6 months and 12 months postlesion, respectively. In summary, partial immunolesions resulted in partial region-specific and time-dependent recoveries of cholinergic activity in the target areas of the basal forebrain after a partial elimination of CBFNs and a return to basal levels of NGF protein consistent with the hypothesis that the remaining CBFNs compensated for losses of ChAT and NGF due to changes in cholinergic innervation of basal forebrain target areas.",
    keywords = "192 IgG-saporin, Acetylcholinesterase, Choline acetyltransferase, Cholinergic basal forebrain neuron, Immunolesion, Nerve growth factor, Regeneration",
    author = "Zezong Gu and Juan Yu and Perez-Polo, {J. Regino}",
    year = "1998",
    month = "8",
    day = "10",
    doi = "10.1016/S0006-8993(98)00579-4",
    language = "English (US)",
    volume = "801",
    pages = "190--197",
    journal = "Brain Research",
    issn = "0006-8993",
    publisher = "Elsevier",
    number = "1-2",

    }

    TY - JOUR

    T1 - Long term changes in brain cholinergic markers and nerve growth factor levels after partial immunolesion

    AU - Gu, Zezong

    AU - Yu, Juan

    AU - Perez-Polo, J. Regino

    PY - 1998/8/10

    Y1 - 1998/8/10

    N2 - There are deficits in cholinergic basal forebrain neurons (CBFNs) in the aged brain and patients suffering Alzheimer's disease associated with a partial loss of the CBFNs. To mimic this partial loss and assess its long term effects on residual cholinergic activity and resultant target-derived nerve growth factor (NGF) levels, we produced a partial immunolesion to CBFNs with 192 IgG-saporin, an immunotoxin selectively taken up by p75(NTR)- bearing neurons. We measured two cholinergic markers, choline acetyltransferase (CHAT) and acetylcholinesterase (ACHE) activity, and NGF protein levels at 10 days, 1, 6 and 12 months postlesion. There were no significant changes in the cholinergic markers and the NGF protein levels in the sham-treated animal controls during the one year experiment. Ten days after 192 IgG-saporin treatment, ChAT activity decreased to 35-50% of controls in the olfactory bulb, hippocampus, and cortex. There was a minor but significant recovery of ChAT activity one year after the immunolesion in the hippocampus. Changes in ACHE activity mirrored the ChAT changes but were less robust. There were transient increases in NGF protein levels in the hippocampus and cortex that returned to basal levels at 6 months and 12 months postlesion, respectively. In summary, partial immunolesions resulted in partial region-specific and time-dependent recoveries of cholinergic activity in the target areas of the basal forebrain after a partial elimination of CBFNs and a return to basal levels of NGF protein consistent with the hypothesis that the remaining CBFNs compensated for losses of ChAT and NGF due to changes in cholinergic innervation of basal forebrain target areas.

    AB - There are deficits in cholinergic basal forebrain neurons (CBFNs) in the aged brain and patients suffering Alzheimer's disease associated with a partial loss of the CBFNs. To mimic this partial loss and assess its long term effects on residual cholinergic activity and resultant target-derived nerve growth factor (NGF) levels, we produced a partial immunolesion to CBFNs with 192 IgG-saporin, an immunotoxin selectively taken up by p75(NTR)- bearing neurons. We measured two cholinergic markers, choline acetyltransferase (CHAT) and acetylcholinesterase (ACHE) activity, and NGF protein levels at 10 days, 1, 6 and 12 months postlesion. There were no significant changes in the cholinergic markers and the NGF protein levels in the sham-treated animal controls during the one year experiment. Ten days after 192 IgG-saporin treatment, ChAT activity decreased to 35-50% of controls in the olfactory bulb, hippocampus, and cortex. There was a minor but significant recovery of ChAT activity one year after the immunolesion in the hippocampus. Changes in ACHE activity mirrored the ChAT changes but were less robust. There were transient increases in NGF protein levels in the hippocampus and cortex that returned to basal levels at 6 months and 12 months postlesion, respectively. In summary, partial immunolesions resulted in partial region-specific and time-dependent recoveries of cholinergic activity in the target areas of the basal forebrain after a partial elimination of CBFNs and a return to basal levels of NGF protein consistent with the hypothesis that the remaining CBFNs compensated for losses of ChAT and NGF due to changes in cholinergic innervation of basal forebrain target areas.

    KW - 192 IgG-saporin

    KW - Acetylcholinesterase

    KW - Choline acetyltransferase

    KW - Cholinergic basal forebrain neuron

    KW - Immunolesion

    KW - Nerve growth factor

    KW - Regeneration

    UR - http://www.scopus.com/inward/record.url?scp=0032504558&partnerID=8YFLogxK

    UR - http://www.scopus.com/inward/citedby.url?scp=0032504558&partnerID=8YFLogxK

    U2 - 10.1016/S0006-8993(98)00579-4

    DO - 10.1016/S0006-8993(98)00579-4

    M3 - Article

    C2 - 9729378

    AN - SCOPUS:0032504558

    VL - 801

    SP - 190

    EP - 197

    JO - Brain Research

    JF - Brain Research

    SN - 0006-8993

    IS - 1-2

    ER -