Increasing brain N‐acetylneuraminic acid alleviates hydrocephalus‐induced neurological deficits

Abstract

AimsThis metabolomic study aimed to evaluate the role of N‐acetylneuraminic acid (Neu5Ac) in the neurological deficits of normal pressure hydrocephalus (NPH) and its potential therapeutic effect.MethodsWe analyzed the metabolic profiles of NPH using cerebrospinal fluid with multivariate and univariate statistical analyses in a set of 42 NPH patients and 38 controls. We further correlated the levels of differential metabolites with severity‐related clinical parameters, including the normal pressure hydrocephalus grading scale (NPHGS). We then established kaolin‐induced hydrocephalus in mice and treated them using N‐acetylmannosamine (ManNAc), a precursor of Neu5Ac. We examined brain Neu5Ac, astrocyte polarization, demyelination, and neurobehavioral outcomes to explore its therapeutic effect.ResultsThree metabolites were significantly altered in NPH patients. Only decreased Neu5Ac levels were correlated with NPHGS scores. Decreased brain Neu5Ac levels have been observed in hydrocephalic mice. Increasing brain Neu5Ac by ManNAc suppressed the activation of astrocytes and promoted their transition from A1 to A2 polarization. ManNAc also attenuated the periventricular white matter demyelination and improved neurobehavioral outcomes in hydrocephalic mice.ConclusionIncreasing brain Neu5Ac improved the neurological outcomes associated with the regulation of astrocyte polarization and the suppression of demyelination in hydrocephalic mice, which may be a potential therapeutic strategy for NPH.

Comparative Site-Specific O-Glycosylation Analysis of the Milk Fat Globule Membrane Proteome in Donkey Colostrum and Mature Milk

“…Studies have shown that sialic acid is essential for neonatal brain neurodevelopment and immune system development because neonates cannot synthesize it themselves and supplement it mainly through exogenous sources . Recent studies have shown that sialic acid can inhibit astrocytic proliferation, promote the polarization of A1 to A2 astrocytes, reduce demyelination, and attenuate neurological deficits induced by hydrocephalus, promoting its use in new therapeutic strategies for normal-pressure hydrocephalus …”

“…16 Recent studies have shown that sialic acid can inhibit astrocytic proliferation, promote the polarization of A1 to A2 astrocytes, reduce demyelination, and attenuate neurological deficits induced by hydrocephalus, promoting its use in new therapeutic strategies for normal-pressure hydrocephalus. 17 The O-glycan core structures of DC and DM MFGM glycoproteins were further observed. As shown in Figure 3A,B, both DC and DM MFGM glycoprotein O-glycans were predominantly mucin-type core structures, with 38.56% core-2 glycans, 25.77% core-4 glycans, 19.67% core-3 glycans, and 14.16% core-1 glycans in DC and 28.89% core-2 glycans, 25.1% core-4 glycans, 23.39% core-1 glycans, and 21.14% core-3 glycans in DM.…”