Enhanced GABAergic immunoreactivity in hippocampal neurons and astroglia of multiple sclerosis patients

Svenja Kiljan, Marloes Prins, Bart M. Baselmans, John G. J. M. Bol, Geert J. Schenk, Anne-Marie van Dam

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Cognitive dysfunction occurs frequently in multiple sclerosis (MS). Research suggests that hippocampal lesions and GABAergic neurotransmitter changes contribute to cognitive dysfunction. In the present study, we aim to determine the cellular changes in GABAergic expression in MS hippocampus related to inflammation and demyelination. To this end, the presence and inflammatory activity of demyelinating lesions was determined by immunohistochemistry in human postmortem hippocampal tissue of 15 MS patients and 9 control subjects. Subsequently, GABAergic cells were visualized using parvalbumin (PV) and glutamate acid decarboxylase 67 (GAD67) markers. Fluorescent colabeling was performed of GAD67 with neuronal nuclei, PV, astrocytic glial fibrillary acidic protein, or vesicular GABA transporter. We observed increased GAD67-positive (GAD67þ) neuron and synapse numbers in the CA1 of MS patients with active hippocampal lesions, not due to neurogenesis. The number and size of PV-positive neurons remained unchanged. GAD67þastrocytes were more numerous in hippocampal white matter than grey matter lesions. Additionally, in MS patients with active hippocampal lesions GAD67þastrocyte surface area was increased. Disturbed cognition was most prevalent in MS patients with active hippocampal lesions. Summarizing, increased GAD67 immunoreactivity occurs in neurons and astrocytes and relates to hippocampal inflammation and possibly disturbed cognition in MS.
Original languageEnglish
Pages (from-to)480-491
JournalJournal of Neuropathology and Experimental Neurology
Volume78
Issue number6
DOIs
Publication statusPublished - 1 Jan 2019

Cite this

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title = "Enhanced GABAergic immunoreactivity in hippocampal neurons and astroglia of multiple sclerosis patients",
abstract = "Cognitive dysfunction occurs frequently in multiple sclerosis (MS). Research suggests that hippocampal lesions and GABAergic neurotransmitter changes contribute to cognitive dysfunction. In the present study, we aim to determine the cellular changes in GABAergic expression in MS hippocampus related to inflammation and demyelination. To this end, the presence and inflammatory activity of demyelinating lesions was determined by immunohistochemistry in human postmortem hippocampal tissue of 15 MS patients and 9 control subjects. Subsequently, GABAergic cells were visualized using parvalbumin (PV) and glutamate acid decarboxylase 67 (GAD67) markers. Fluorescent colabeling was performed of GAD67 with neuronal nuclei, PV, astrocytic glial fibrillary acidic protein, or vesicular GABA transporter. We observed increased GAD67-positive (GAD67{\th}) neuron and synapse numbers in the CA1 of MS patients with active hippocampal lesions, not due to neurogenesis. The number and size of PV-positive neurons remained unchanged. GAD67{\th}astrocytes were more numerous in hippocampal white matter than grey matter lesions. Additionally, in MS patients with active hippocampal lesions GAD67{\th}astrocyte surface area was increased. Disturbed cognition was most prevalent in MS patients with active hippocampal lesions. Summarizing, increased GAD67 immunoreactivity occurs in neurons and astrocytes and relates to hippocampal inflammation and possibly disturbed cognition in MS.",
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Enhanced GABAergic immunoreactivity in hippocampal neurons and astroglia of multiple sclerosis patients. / Kiljan, Svenja; Prins, Marloes; Baselmans, Bart M.; Bol, John G. J. M.; Schenk, Geert J.; van Dam, Anne-Marie.

In: Journal of Neuropathology and Experimental Neurology, Vol. 78, No. 6, 01.01.2019, p. 480-491.

Research output: Contribution to journalArticleAcademicpeer-review

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AU - Schenk, Geert J.

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AB - Cognitive dysfunction occurs frequently in multiple sclerosis (MS). Research suggests that hippocampal lesions and GABAergic neurotransmitter changes contribute to cognitive dysfunction. In the present study, we aim to determine the cellular changes in GABAergic expression in MS hippocampus related to inflammation and demyelination. To this end, the presence and inflammatory activity of demyelinating lesions was determined by immunohistochemistry in human postmortem hippocampal tissue of 15 MS patients and 9 control subjects. Subsequently, GABAergic cells were visualized using parvalbumin (PV) and glutamate acid decarboxylase 67 (GAD67) markers. Fluorescent colabeling was performed of GAD67 with neuronal nuclei, PV, astrocytic glial fibrillary acidic protein, or vesicular GABA transporter. We observed increased GAD67-positive (GAD67þ) neuron and synapse numbers in the CA1 of MS patients with active hippocampal lesions, not due to neurogenesis. The number and size of PV-positive neurons remained unchanged. GAD67þastrocytes were more numerous in hippocampal white matter than grey matter lesions. Additionally, in MS patients with active hippocampal lesions GAD67þastrocyte surface area was increased. Disturbed cognition was most prevalent in MS patients with active hippocampal lesions. Summarizing, increased GAD67 immunoreactivity occurs in neurons and astrocytes and relates to hippocampal inflammation and possibly disturbed cognition in MS.

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