Expression of parvalbumin, osteopontin and glypican 4 in neurons of lumbar region distant from the epicenter of traumatic spinal cord injury

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Abstract

Spinal cord injury (SCI) is manifested by pathologic changes in the areas significantly distant from the area of primary injury. In order to find new potential therapeutic targets to restore motor function, it is particularly relevant to identify the causes and mechanisms of these shifts in the lumbar spinal cord when injury occurs in the proximal spinal cord. On the model of dosed SCI the expression of Ca-binding protein parvalbumin (PARV), osteopontin (OPN) and glypican 4 (GPC4) in neurons of laminae VII, VIII and IX within segments L3–4 on 7 and 60 days of the experiment was studied. Laminas VII and IX show a decrease in the number of PARV+ neurons during the acute and chronic phase of SCI, which may indicate a decrease in calcium binding in ventral horn neurons at the level of segments L3–4. Decreased PARV expression in these neurons indicates an increased risk of their vulnerability and impaired motor function. The pattern of OPN expression in lumbar horn neurons distant from the epicenter of traumatic injury was studied for the first time. In all the studied laminae in the ventral horns of the gray matter, we did not observe shifts in the number of OPN+ neurons both in the acute and chronic phases of SCI. In lamina IX of the lumbar spinal cord, we found an increase in the number of GPC4+ neurons in the acute posttraumatic period, which can be regarded as a key positive adaptive reaction of neurons in the lumbar spinal cord remote from the epicenter of injury. The assessment of this reaction as positive is based on the data on the binding of GPC4 anchored on the neuron surface to various molecules with neuroprotective activity and stimulating neuroregeneration.

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About the authors

O. N. Tutova

Kazan (Volga region) Federal University

Email: ikabdesh@gmail.com
Russian Federation, Kazan

I. M. Kabdesh

Kazan (Volga region) Federal University

Author for correspondence.
Email: ikabdesh@gmail.com
Russian Federation, Kazan

Ya. O. Mukhamedshina

Kazan (Volga region) Federal University; Kazan State Medical University

Email: ikabdesh@gmail.com
Russian Federation, Kazan; Kazan

Yu. A. Chelyshev

Kazan (Volga region) Federal University; Kazan State Medical University

Email: ikabdesh@gmail.com
Russian Federation, Kazan; Kazan

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2. Fig. 1. Immunofluorescence analysis. Visualization of GPC4 expression in different laminae (VII, VIII, IX) of the anterior horns in the lumbar region (segments L3–4) of the rat spinal cord. Scale bar: 100 µm (10×).

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3. Fig. 2. The number of (a) PARV+, (b) OPN+, (c) GPC4+ neurons in the lamina VII of the anterior horns in the lumbar region (segments L3–4) of the intact and injured at the thoracic level (segment Th8) of the rat spinal cord on the 7th and 60th days after injury (7 and 60 dpi – days post injury); p < 0.05, Kruskal–Wallis test.

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4. Fig. 3. The number of (a) PARV+, (b) OPN+, (c) GPC4+ neurons in the VIII lamina of the anterior horns in the lumbar region (segments L3–4) of the intact and injured at the thoracic level (segment Th8) spinal cord of the rat on the 7th and 60th days after injury (7 and 60 dpi); p < 0.05, Kruskal–Wallis test.

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5. Fig. 4. The number of (a) PARV+, (b) OPN+, (c) GPC4+ neurons in the lamina IX of the anterior horns in the lumbar region (segments L3–4) of the intact and injured at the thoracic level (segment Th8) spinal cord of the rat on the 7th and 60th days after injury (7 and 60 dpi – days post injury); p < 0.05, Kruskal – Wallis test.

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6. Fig. 5. Changes in the integrated fluorescence intensity (MIF units – mean intensity of fluorescence) of GPC4 in the anterior horns of the lumbar region (segments L3–4) of the intact and injured at the level of the thoracic region (segment Th8) of the rat spinal cord on the 7th and 60th days after injury (7 and 60 dpi – days post injury); p < 0.05, Tukey test.

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7. Fig. 6. Immunofluorescence analysis visualizing the expression of (a) PARV (red), (b) OPN (yellow), and (c) GPC4 (red) in the anterior horn (lamina IX) of the lumbar region (segments L3–4) of the rat spinal cord. Scale bar: 50 μm (20×).

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