Enhanced GABAergic Immunoreactivity in Hippocampal Neurons and Astroglia of Multiple Sclerosis Patients.

Autor:	Kiljan S; Department of Anatomy and Neurosciences, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam, The Netherlands., Prins M; Department of Anatomy and Neurosciences, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam, The Netherlands., Baselmans BM; Department of Anatomy and Neurosciences, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam, The Netherlands.; Bart M. Baselmans, Department of Biological Psychology, VU University, Amsterdam, The Netherlands., Bol JGJM; Department of Anatomy and Neurosciences, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam, The Netherlands., Schenk GJ; Department of Anatomy and Neurosciences, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam, The Netherlands., van Dam AM; Department of Anatomy and Neurosciences, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam, The Netherlands.
Jazyk:	angličtina
Zdroj:	Journal of neuropathology and experimental neurology [J Neuropathol Exp Neurol] 2019 Jun 01; Vol. 78 (6), pp. 480-491.
DOI:	10.1093/jnen/nlz028
Abstrakt:	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+) 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+ astrocytes were more numerous in hippocampal white matter than grey matter lesions. Additionally, in MS patients with active hippocampal lesions GAD67+ 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. (© 2019 American Association of Neuropathologists, Inc.)
Databáze:	MEDLINE
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