Glutamate Decarboxylase (GAD) is not Detectable on the Surface of Rat Islet Cells Examined by Cytofluorometry and Complement-Dependent Antibody-Mediated Cytotoxicity of Monoclonal GAD Antibodies

Ziegler, B; Augstein, Petra; Schroder, D.K.; Mauch, Ludwig; Hahmann, Jens; Schlosser, Michael; Ziegler, M.

doi:10.1055/s-2007-979121

Cited by 11 publications

(6 citation statements)

References 9 publications

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“…There is 65% amino acid sequence homology between the two isoforms (Karlsen et al, 1991;Li et al, 1995, Bu et al, 1992. The hybridoma secreting the antibody to GAD 65/67 was generated by fusion of splenocytes from a mouse immunized with fragments of recombinant human GAD 65 fused to glutathione-S-transferase (Ziegler et al, 1996).…”

Section: Glutamic Acid Decarboxylasementioning

confidence: 99%

Calretinin inputs are confined to motoneurons for upward eye movements in monkey

Zeeh

Hess²,

Horn

2013

J of Comparative Neurology

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Motoneurons of extraocular muscles are controlled by different premotor pathways, whose selective damage may cause directionally selective eye movement disorders. The fact that clinical disorders can affect only one direction, e.g., isolated up-/downgaze palsy or up-/downbeat nystagmus, indicates that up- and downgaze pathways are organized separately. Recent work in monkey revealed that a subpopulation of premotor neurons of the vertical eye movement system contains the calcium-binding protein calretinin (CR). With combined tract-tracing and immunofluorescence, the motoneurons of vertically pulling eye muscles in monkey were investigated for the presence of CR-positive afferent terminals. In the oculomotor nucleus, CR was specifically found in punctate profiles contacting superior rectus and inferior oblique motoneurons, as well as levator palpebrae motoneurons, all of which participate in upward eye movements. Double-immunofluorescence labeling revealed that CR-positive terminals lacked the γ-aminobutyric acid (GABA)-synthesizing enzyme glutamate decarboxylase, which is present in inhibitory afferents to all motoneurons mediating vertical eye movements. Therefore, CR-containing afferents are considered to be excitatory. In conclusion, a strong CR input is confined to motoneurons mediating upgaze, which derive from premotor pathways mediating saccades and smooth pursuit, but not from secondary vestibulo-ocular neurons in the magnocellular part of the medial vestibular nucleus. The functional significance of CR in these connections is unclear, but it may serve as a useful marker to locate upgaze pathways in the human brain.

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Section: Glutamic Acid Decarboxylasementioning

confidence: 99%

Calretinin inputs are confined to motoneurons for upward eye movements in monkey

Zeeh

Hess²,

Horn

2013

J of Comparative Neurology

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“…42 The accessibility of dif-ferent GAD antigens to antibodies may also differ depending on GAD antigen exposure on the cell surface during GABA exocytosis. 43 Most importantly, other antigenic targets that have different properties and distribution may be responsible in SPS.…”

Section: Commentmentioning

confidence: 99%

Brain γ-Aminobutyric Acid Changes in Stiff-Person Syndrome

Levy¹,

Levy-Reis²,

Fujii³

et al. 2005

Arch Neurol

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Background: Patients with stiff-person syndrome (SPS) have circulating antibodies against glutamic acid decarboxylase, the rate-limiting enzyme responsible for the synthesis of ␥-aminobutyric acid (GABA). Although the patients' symptoms of stiffness and unexpected spasms can be explained on the basis of reduced or impaired inhibitory neurotransmitters, such as GABA, it is unclear whether the level of GABA in the brains of these patients is reduced and, if so, whether the reduction is due to anti-glutamic acid decarboxylase antibodies. Objective: To measure GABA levels in the brains of patients with SPS.

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“…The antibody GC 3108 recognizes a linear epitope at the C-terminus of rat GAD, common to both isoforms. The hybridoma secreting the antibody to GAD 65/67 was generated by fusion of splenocytes from a mouse immunized with fragments of recombinant human GAD 65 fused to glutathione-S-transferase (Ziegler et al, 1996 ).…”

Section: Methodsmentioning

confidence: 99%

Calretinin as a Marker for Premotor Neurons Involved in Upgaze in Human Brainstem

et al. 2015

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Eye movements are generated by different premotor pathways. Damage to them can cause specific deficits of eye movements, such as saccades. For correlative clinico-anatomical post-mortem studies of cases with eye movement disorders it is essential to identify the functional cell groups of the oculomotor system in the human brain by marker proteins. Based on monkey studies, the premotor neurons of the saccadic system can be identified by the histochemical markers parvalbumin (PAV) and perineuronal nets in humans. These areas involve the interstitial nucleus of Cajal (INC) and the rostral interstitial nucleus of the medial longitudinal fascicle (RIMLF), which both contain premotor neurons for upgaze and downgaze. Recent monkey and human studies revealed a selective excitatory calretinin (CR)-positive input to the motoneurons mediating upgaze, but not to those for downgaze. Three premotor regions were identified as sources of CR input in monkey: y-group, INC and RIMLF. These findings suggest that the expression pattern of parvalbumin and CR may help to identify premotor neurons involved in up- or downgaze. In a post-mortem study of five human cases without neurological diseases we investigated the y-group, INC and RIMLF for the presence of parvalbumin and CR positive neurons including their co-expression. Adjacent thin paraffin sections were stained for the aggrecan (ACAN) component of perineuronal nets, parvalbumin or CR and glutamate decarboxylase. The comparative analysis of scanned thin sections of INC and RIMLF revealed medium-sized parvalbumin positive neurons with and without CR coexpression, which were intermingled. The parvalbumin/CR positive neurons in both nuclei are considered as excitatory premotor upgaze neurons. Accordingly, the parvalbumin-positive neurons lacking CR are considered as premotor downgaze neurons in RIMLF, but may in addition include inhibitory premotor upgaze neurons in the INC as indicated by co-expression of glutamate decarboxylase in a subpopulation. CR-positive neurons ensheathed by perineuronal nets in the human y-group are considered as the homolog premotor neurons described in monkey, projecting to superior rectus (SR) and inferior oblique (IO) motoneurons. In conclusion, combined immunostaining for parvalbumin, perineuronal nets and CR may well be suited for the specific identification and subsequent analysis of premotor upgaze pathways in clinical cases of isolated up- or downgaze deficits.

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Glutamate Decarboxylase (GAD) is not Detectable on the Surface of Rat Islet Cells Examined by Cytofluorometry and Complement-Dependent Antibody-Mediated Cytotoxicity of Monoclonal GAD Antibodies

Cited by 11 publications

References 9 publications

Calretinin inputs are confined to motoneurons for upward eye movements in monkey

Calretinin inputs are confined to motoneurons for upward eye movements in monkey

Brain γ-Aminobutyric Acid Changes in Stiff-Person Syndrome

Calretinin as a Marker for Premotor Neurons Involved in Upgaze in Human Brainstem

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