Intraneuronal IgG in the central nervous system

Fabian, Roderic H.; Ritchie, Teresa C.

doi:10.1016/0022-510x(86)90150-4

Cited by 53 publications

(23 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Transport of antibodies within the CNS has not been thoroughly investigated but IgG transport within and across cells in the periphery is essential for effective humoral immunity. Also, several studies have shown that antibodies can be found within neurons, which supports the feasibility of our approach (Fabian and Ritchie, 1986;Fabian and Petroff, 1987;Liu et al, 1989;Dietzschold et al, 1992;Aihara et al, 1994;Mohamed et al, 2002). The antibodies may enter the cells via pinocytosis (e.g., receptormediated endocytosis or fluid-phase endocytosis) (Lobo et al, 2004).…”

mentioning

confidence: 69%

“…Clearance of extracellular tangles may reduce associated pathology, and numerous reports of neuronal uptake of antibodies suggest that intracellular tangles and pretangles may also be affected (Fabian and Ritchie, 1986;Fabian and Petroff, 1987;Liu et al, 1989;Dietzschold et al, 1992;Aihara et al, 1994;Mohamed et al, 2002). Toward this end, homozygous P301L mice were immunized with a phosphorylated tau epitope with subsequent analysis of tau pathology and associated functional impairments.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Immunotherapy Targeting Pathological Tau Conformers in a Tangle Mouse Model Reduces Brain Pathology with Associated Functional Improvements

Asuni

Boutajangout²,

Quartermain³

et al. 2007

J. Neurosci.

464

524

View full text Add to dashboard Cite

Immunotherapies for various neurodegenerative diseases have recently emerged as a promising approach for clearing pathological protein conformers in these disorders. This type of treatment has not been assessed in models that develop neuronal tau aggregates as observed in frontotemporal dementia and Alzheimer's disease. Here, we present that active immunization with a phosphorylated tau epitope, in P301L tangle model mice, reduces aggregated tau in the brain and slows progression of the tangle-related behavioral phenotype. Females had more tau pathology than males but were also more receptive to the immunotherapy. The tau antibodies generated in these animals recognized pathological tau on brain sections. Performance on behavioral assays that require extensive motor coordination correlated with tau pathology in corresponding brain areas, and antibody levels against the immunogen correlated inversely with tau pathology. Interestingly, age-dependent autoantibodies that recognized recombinant tau protein but not the immunogen were detected in the P301L mice. To confirm that anti-tau antibodies could enter the brain and bind to pathological tau, FITC-tagged antibodies purified from a P301L mouse, with a high antibody titer against the immunogen, were injected into the carotid artery of P301L mice. These antibodies were subsequently detected within the brain and colocalized with PHF1 and MC1 antibodies that recognize pathological tau. Currently, no treatment is available for clearing tau aggregates. Our present findings may lead to a novel therapy targeting one of the major hallmarks of Alzheimer's disease and frontotemporal dementia.

show abstract

mentioning

confidence: 69%

Section: Introductionmentioning

confidence: 99%

Immunotherapy Targeting Pathological Tau Conformers in a Tangle Mouse Model Reduces Brain Pathology with Associated Functional Improvements

Asuni

Boutajangout²,

Quartermain³

et al. 2007

J. Neurosci.

464

524

View full text Add to dashboard Cite

show abstract

“…26 Deposition of IgG on neurons may result from their function as a ''sink'' for extravasated plasma proteins after changes in their membrane permeability due to injury, 27,28 or as a result of retrograde transport from outside the CNS through motoneurons of the spinal cord, whose axons project into the periphery. [29][30][31][32][33] Similarly, IgG binding to astrocytes may result from sequestration of immunoglobulins that are extravasated into the CNS due to the breakdown of the BSCB in order to maintain homeostasis after injury. 19 To test the latter hypothesis, we measured binding of serum immunoglobulins from rats with sham or cSCI injury at 2 weeks to fixed astrocytes, which cannot engage in sequestration.…”

Section: Discussionmentioning

confidence: 99%

Characterization of the Antibody Response after Cervical Spinal Cord Injury

Ulndreaj

Τζέκου

Mothe

et al. 2017

Journal of Neurotrauma

View full text Add to dashboard Cite

The immune system plays a critical and complex role in the pathobiology of spinal cord injury (SCI), exerting both beneficial and detrimental effects. Increasing evidence suggests that there are injury level-dependent differences in the immune response to SCI. Patients with traumatic SCI have elevated levels of circulating autoantibodies against components of the central nervous system, but the role of these antibodies in SCI outcomes remains unknown. In rodent models of mid-thoracic SCI, antibody-mediated autoimmunity appears to be detrimental to recovery. However, whether autoantibodies against the spinal cord are generated following cervical SCI (cSCI), the most common level of injury in humans, remains undetermined. To address this knowledge gap, we investigated the antibody responses following cSCI in a rat model of injury. We found increased immunoglobulin G (IgG) and IgM antibodies in the spinal cord in the subacute phase of injury (2 weeks), but not in more chronic phases (10 and 20 weeks). At 2 weeks post-cSCI, antibodies were detected at the injury epicenter and co-localized with the astroglial scar and neurons of the ventral horn. These increased levels of antibodies corresponded with enhanced activation of immune responses in the spleen. Higher counts of antibodysecreting cells were observed in the spleen of injured rats. Further, increased levels of secreted IgG antibodies and enhanced proliferation of T-cells in splenocyte cultures from injured rats were found. These findings suggest the potential development of autoantibody responses following cSCI in the rat. The impact of the post-traumatic antibody responses on functional outcomes of cSCI is a critical topic that requires further investigation.

show abstract

“…Staining within neurons was granular and tended to be concentrated around, but was excluded from, the nucleus, and extended into proximal dendrites. This staining was noted in all major brainstem and spinal cord motor nuclei, as has been described previously (LaRocca and Wiley, 1988;Fabian and Ritchie, 1986). …”

Section: Perfusion-fixed Tissue: General Observationsmentioning

confidence: 99%

Poor reliability of immunocytochemical localization of IgG in immersion-fixed tissue from the central nervous system.

Fabian

1992

J Histochem Cytochem.

View full text Add to dashboard Cite

The effect of furation technique and post mortem-to-fixation interval in immersion-fined tissue from the central nervous system on immunocytochemical staining for the presence of an immunoglobulin was determined in mice. Immersionfixed tissue was found to be inferior to perfusion-fixed tissue for immunocytochemical staining of this serum protein.Unlike what has been observed for other antigens, the quality of staining for IgG in immersion-fixed tissue decreased to unacceptable levels if the post mortem-to-fixation interval was increased to more than a few hours. This effect may be secondary to the rapid post-mortem disintegration of the blood-brain barrier and a resulting diffusion of serum proteins into surrounding tissue from the vasculature. ( J Histochem Cytochem 40:987-991, 1992)

show abstract

Intraneuronal IgG in the central nervous system

Cited by 53 publications

References 17 publications

Immunotherapy Targeting Pathological Tau Conformers in a Tangle Mouse Model Reduces Brain Pathology with Associated Functional Improvements

Immunotherapy Targeting Pathological Tau Conformers in a Tangle Mouse Model Reduces Brain Pathology with Associated Functional Improvements

Characterization of the Antibody Response after Cervical Spinal Cord Injury

Poor reliability of immunocytochemical localization of IgG in immersion-fixed tissue from the central nervous system.

Contact Info

Product

Resources

About