Effect of 1α,25‐dihydroxyvitamin D3 in embryonic hippocampal cells

Abstract

Although the role of 1alpha,25-dihydroxyvitamin D3 in calcium homeostasis of bone tissue is clear, evidence of the involvement of vitamin D3 in the central nervous system functions is increasing. In fact, vitamin D3 regulates vitamin D receptor and nerve growth factor expression, modulates brain development, and reverses experimental autoimmune encephalomyelitis. Only few studies, however, address vitamin D3 effect on embryonic hippocampal cell differentiation. In this investigation, the HN9.10e cell line was used as experimental model; these cells, that are a somatic fusion product of hippocampal cells from embryonic day-18 C57BL/6 mice and N18TG2 neuroblastoma cells, show morphological and cytoskeletal features similar to their neuronal precursors. By this model, we have studied the time course of vitamin D3 localization in the nucleus and its effect on proteins involved in proliferation and/or differentiation. We found that the translocation of vitamin D3 from cytoplasm to the nucleus is transient, as the maximal nuclear concentration is reached after 10 h of incubation with (3)H-vitamin D3 and decreases to control values by 12 h. The appearance of differentiation markers such as Bcl2, NGF, STAT3, and the decrease of proliferation markers such as cyclin-1 and PCNA are late events. Moreover, physiological concentrations of vitamin D3 delay cell proliferation and induce cell differentiation of embryonic cells characterized by modification of soma lengthening and formation of axons and dendrites.

Therapeutic effects of vitamin D3 on motor functions following experimental spinal cord injury

“…Yapılan çalışmalarda gösterilmiş ki vitamin D VDR üzerinden beyin kaynaklı nörotrofik faktör, sinir büyüme faktörü ve nörotrofin 3'ü kodlayan genlerin ekspresyonunu regule etmektedir (48). Hipokampal hücre kültürlerinde vitamin D 3 'ün eklenmesi ile nörotrofinlerin ekspresyonunun uyarıldığı ve nöronların büyümesinin arttığı gözlenmiş (49). Başka bir çalışmada sıçan beyinlerinde vitamin D 3 ortamdan uzaklaştırıldığında nöronal büyüme faktörlerinin ekspresyonunun azaldığı saptanmış (50).…”

O sistema endocrinológico vitamina D

“…Cérebro: em animais de laboratório demonstrou-se que o VDR apresenta ações estimulatórias do fator de crescimento neural e moduladoras do desenvolvimento cerebral (46). Como várias células do cérebro humano expressam a CYP27B1 e o VDR (47), infere-se, a partir de estudos moleculares, que a 1,25(OH) 2 D exerça ações autócrinas e parácrinas na regulação do desenvolvimento e nas funções cerebrais, mas as evidências atuais ainda não são suficientes para confirmar e explicar essas ações no cérebro humano.…”

Changes in the expression of the vitamin D receptor and LVSCC-A1C in the rat hippocampus submitted to single prolonged stress

“…The action of vitamin D is mediated by the vitamin D receptor (VDR), a ligand-activated transcription factor (8). VDR is considered to be a nuclear receptor that is ubiquitously expressed in a wide variety of organs or tissues, including in the muscle, adipose tissue, bone (9), cerebral cortex and hippocampus (6,10). Genetic variance in the VDR gene affects the susceptibility to age-related changes in cognitive functioning and depressive symptoms (11).…”