Title : Retracted: Allopregnanolone restores the tyrosine hydroxylase-positive neurons and motor performance in a 6-OHDA-injected mouse model.

Pub. Date : 2020 Oct

PMID : 32602622






6 Functional Relationships(s)
Download
Sentence
Compound Name
Protein Name
Organism
1 AIMS: It has been reported that allopregnanolone (APalpha) promotes the neurogenesis of the neural progenitor cells (NPCs) in the subventricular zone (SVZ) and prevents the decrease of dopaminergic neurons in 6-hydroxydopamine (6-OHDA)-treated mice by binding to gamma-aminobutyric acid A receptor (GABAAR) and then opening voltage-gated L-type Ca2+ channel, but the underlying mechanisms remain elusive. Pregnanolone gamma-aminobutyric acid (GABA) A receptor, subunit gamma 2 Mus musculus
2 AIMS: It has been reported that allopregnanolone (APalpha) promotes the neurogenesis of the neural progenitor cells (NPCs) in the subventricular zone (SVZ) and prevents the decrease of dopaminergic neurons in 6-hydroxydopamine (6-OHDA)-treated mice by binding to gamma-aminobutyric acid A receptor (GABAAR) and then opening voltage-gated L-type Ca2+ channel, but the underlying mechanisms remain elusive. Pregnanolone gamma-aminobutyric acid (GABA) A receptor, subunit gamma 2 Mus musculus
3 METHODS: 6-OHDA-treated mice and primary cultured midbrain cells were administrated with APalpha and GABAAR antagonist bicuculline (Bic), and the proliferation and differentiation of NPCs, the tyrosine hydroxylase (TH)-positive neurons and their fibers, the expression levels of CaMKIIdelta3 and brain-derived neurotrophic factor (BDNF), and motor functions were measured using ELISA, immunohistochemical staining, real-time RT-PCR, Western blot, and behavioral test. Oxidopamine gamma-aminobutyric acid (GABA) A receptor, subunit gamma 2 Mus musculus
4 RESULTS: Allopregnanolone significantly promoted the phosphorylation of cytoplasmic CaMKIIdelta3 and its nuclear translocation by binding to GABAAR, which, in turn, increased the expression levels of BDNF. Pregnanolone gamma-aminobutyric acid (GABA) A receptor, subunit gamma 2 Mus musculus
5 CONCLUSIONS: Allopregnanolone may directly activate GABAAR, which, in turn, enhance the proliferation and differentiation of NPCs via upregulating the expression levels of CaMKIIdelta3, and finally contribute to the restoration of dopaminergic neurons in 6-OHDA-treated mice. Pregnanolone gamma-aminobutyric acid (GABA) A receptor, subunit gamma 2 Mus musculus
6 CONCLUSIONS: Allopregnanolone may directly activate GABAAR, which, in turn, enhance the proliferation and differentiation of NPCs via upregulating the expression levels of CaMKIIdelta3, and finally contribute to the restoration of dopaminergic neurons in 6-OHDA-treated mice. Oxidopamine gamma-aminobutyric acid (GABA) A receptor, subunit gamma 2 Mus musculus