Neuroplastin Expression in the Hippocampus of Mice Lacking Complex Gangliosides

Abstract

We report changes in neuroplastin gene and protein expression in the hippocampus of B4galnt1 null mice, which lacks complex ganglioside structures, compared with that of wild-type mice. Neuroplastin mRNA expression was significantly higher in the hippocampi of B4galnt1 null mice than in wild-type mice. Moreover, Western blot analysis shows increased neuroplastin protein levels of neuroplastin-55 isoform in B4galnt1 null hippocampal homogenates. Immunohistochemistry revealed a substantially different distribution of neuroplastin immunoreactivity in sagittal sections of the hippocampi derived from B4galnt1 null in comparison with those from wild-type mice. Most strikingly, B4galnt1 null mice had relatively little neuroplastin immunoreactivity in the pyramidal layer of CA1 and CA3, whereas wild-type mice had strong neuroplastin staining of pyramidal cells. Results of this study support the hypothesis that alterations of brain ganglioside expression influence the expression of neuroplastin. As both neuroplastin and gangliosides have important roles in synaptic transmission, synaptic plasticity, and neurite outgrowth, it will be of particular interest to unravel the molecular mechanisms underlying the relationship between ganglioside composition and neuroplastin transcript and protein expression in the mammalian nervous system.

The Neuroplastin adhesion molecules: key regulators of neuronal plasticity and synaptic function

“…Interestingly, Neuroplastin expression is linked to the ganglioside composition of neural membranes (Mlinac et al 2012). In mice deficient for the enzyme B4galnt1 and thus lacking complex gangliosides, Neuroplastin mRNA and particularly Np55 protein expression is increased in the hippocampus.…”

Neuroplastin in human cognition: review of literature and future perspectives

“…Our group reported that Np positioning within the neuronal membrane is highly sensitive on its particular membrane lipid environment in murine brain tissue [30]. Specifically, compositional changes of membrane glycosphingolipids-gangliosides alter Np gene and protein expression, as well its immunolocalization and distribution in the mouse hippocampus [30]. The finding that implies effects of membrane lipid composition on functionality of Np has been recently supported by a study describing specific rearrangements of Np and gangliosides upon chronic stress and aging in the rat hippocampus [31].…”

“…Further aspect of molecular complexity and machineries underlying processes related to memory, learning, and cognition encompasses so far a well-recognized influence of neuronal membrane composition, organization, and dynamics on synaptic plasticity [28,29]. Our group reported that Np positioning within the neuronal membrane is highly sensitive on its particular membrane lipid environment in murine brain tissue [30]. Specifically, compositional changes of membrane glycosphingolipids-gangliosides alter Np gene and protein expression, as well its immunolocalization and distribution in the mouse hippocampus [30].…”

Neuronal Signaling by Thy-1 in Nanodomains With Specific Ganglioside Composition: Shall We Open the Door to a New Complexity?

“…In the human brain, and very similarly in the rodent brain (Figure 2), GM1, GD1a, GD1b, and GT1b together sum up to 97% of the total ganglioside content. Ganglioside distribution has been studied in brain tissue using specific primary antibodies followed by 3-3′-Diaminobenzidine-based staining similarly as for Thy-1 (Heffer-Lauc et al, 2005, 2007) or other CAMs like Neuroplastin (Mlinac et al, 2012; Herrera-Molina et al, 2017; Ilic et al, 2019). However, special caution is required regarding the detergent used during the procedures as inappropriate conditions produce artifacts as drastic as loss and re-distribution of several ganglioside types.…”