Abstract
Neuroserpin is a serine protease inhibitor that regulates the activity of tissue-type plasminogen activator (tPA) in the nervous system. Neuroserpin is strongly expressed during nervous system development as well as during adulthood, when it is predominantly found in regions eliciting synaptic plasticity. In the hippocampus, neuroserpin regulates developmental neurogenesis, synaptic maturation and in adult mice it modulates synaptic plasticity and controls cognitive and social behavior. High expression levels of neuroserpin in the neocortex starting from prenatal stage and persisting during adulthood suggest an important role for the serpin in the formation of this brain region and in the maintenance of cortical functions. In order to uncover neuroserpin function in the murine neocortex, in this work we performed a comprehensive investigation of its expression pattern during development and in the adulthood. Moreover, we assessed the role of neuroserpin in cortex formation by comparing cortical lamination and neuronal maturation between neuroserpin-deficient and control mice. Finally, we evaluated a possible regulatory role of neuroserpin at cortical synapses in neuroserpin-deficient mice. We observed that neuroserpin is expressed starting from the beginning of corticogenesis until adulthood throughout the neocortex in several classes of glutamatergic projection neurons and GABA-ergic interneurons. However, in the absence of neuroserpin we did not detect any alteration either in cortical layer formation, or in neuronal soma size and dendritic length. Furthermore, no significant quantitative changes were observed in the proteome of cortical synapses upon neuroserpin deficiency. We conclude that, although strongly expressed in the neocortex, absence of neuroserpin does not lead to gross developmental abnormalities, and does not perturb the composition of the cortical synaptic proteome.
Highlights
Cognition, sensation, perception, voluntary movements are higher-order brain functions that rely on the ordered architecture of the cerebral cortex
Reelin-positive Cajal-Retzius cells were present in the marginal zone, they did not express neuroserpin, as no colocalization was observed between the two proteins
Neuroserpin expression was clearly visible in the developing cortical plate at E13, where it was found around the nuclei of Tbr1-positive projection neurons
Summary
Sensation, perception, voluntary movements are higher-order brain functions that rely on the ordered architecture of the cerebral cortex. GABA-ergic interneurons are generated from progenitors located in the ganglionic eminence during the same embryonic period as glutamatergic projection neurons and migrate tangentially into the neocortex (de Carlos et al, 1996; Tamamaki et al, 1997; Sultan et al, 2013). Once they reach their terminal destination, neurons undergo maturation by extending dendrites and establishing synaptic contacts with other cells, thereby forming neural circuits (Ohtaka-Maruyama and Okado, 2015). The coordinated generation and migration of cortical neurons is crucial for proper formation and functioning of the neocortex, as impairment of corticogenesis may lead to brain malformations or psychiatric disorders
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