Expression of CRYM in different rat organs during development and its decreased expression in degenerating pyramidal tracts in amyotrophic lateral sclerosis

Abstract

The protein μ-crystallin (CRYM) is a novel component of the marsupial lens that has two functions: it is a key regulator of thyroid hormone transportation and a reductase of sulfur-containing cyclic ketimines. In this study, we examined changes of the expression pattern of CRYM in different rat organs during development using immunohistochemistry and immunoblotting. As CRYM is reportedly expressed in the corticospinal tract, we also investigated CRYM expression in human cases of amyotrophic lateral sclerosis (ALS) using immunohistochemistry. In the rat brain, CRYM was expressed in the cerebral cortex, basal ganglia, hippocampus and corticospinal tract in the early postnatal period. As postnatal development progressed, CRYM expression was restricted to large pyramidal neurons in layers V and VI of the cerebral cortex and pyramidal cells in the deep layer of CA1 in the hippocampus. Even within the same regions, CRYM-positive and negative neurons were distributed in a mosaic pattern. In the kidney, CRYM was expressed in epithelial cells of the proximal tubule and mesenchymal cells of the medulla in the early postnatal period; however, CRYM expression in the medulla was lost as mesenchymal cell numbers decreased with the rapid growth of the medulla. In human ALS brains, we observed marked loss of CRYM in the corticospinal tract, especially distally. Our results suggest that CRYM may play roles in development of cortical and hippocampal pyramidal cells in the early postnatal period, and in the later period, performs cell-specific functions in selected neuronal populations. In the kidney, CRYM may play roles in maturation of renal function. The expression patterns of CRYM may reflect significance of its interactions with T3 or ketimines in these cells and organs. The results also indicate that CRYM may be used as a marker of axonal degeneration in the corticospinal tract.

Identification of a novel mutation in CRYM in a Chinese family with hearing loss using whole‑exome sequencing

“…CRYM has a critical role in the physiological regulation of the activity of thyroid hormone ( 35 ). An experimental study has indicated that CRYM may have a role in the development of cortical and hippocampal pyramidal cells in the early postnatal period ( 36 ). Furthermore, CRYM expression is possibly upregulated through the activator protein-1 (AP-1) site in the promoter ( 37 ).…”

Key Disease Mechanisms Linked to Amyotrophic Lateral Sclerosis in Spinal Cord Motor Neurons

“…Contrary to these findings, thyroid hormone levels did not correlate with prolonged survival in a clinical study including 278 patients with ALS (Zheng et al, 2014 ). Another study reported the expression of protein μ crystalline (CRYM), a key regulator of thyroid hormone transport, is reduced in the corticospinal tract of ALS patients (Hommyo et al, 2018 ). Based on these studies, there is no conclusive evidence between thyroid dysfunction and the development of ALS.…”

Saffron extract (Safr'Inside™) improves anxiety related behaviour in a mouse model of low-grade inflammation through the modulation of the microbiota and gut derived metabolites

“…27 Although the exact function of CRYM/KR remains to be fully elucidated, it may play important roles in neuroprotection, neurotransmission, cell survival and lysine metabolism through interactions with thyroid hormone T3 or ketimines. 82…”