Details

Autor(en) / Beteiligte

• Huguet, Gemma
• Temel, Yasin
• Kádár, Elisabet
• Pol, Sylvana
• Casaca-Carreira, Joao
• Segura-Torres, Pilar
• Jahanshahi, Ali

Titel

Altered expression of dopaminergic cell fate regulating genes prior to manifestation of symptoms in a transgenic rat model of Huntington's disease

Ist Teil von

• Brain research, 2019-06, Vol.1712, p.101-108

Ort / Verlag

Netherlands: Elsevier B.V

Erscheinungsjahr

2019

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• •Dopaminergic cell fate related gene expression is altered in tgHD rats.•Zbtb16 may be a candidate to be regionally tuning dopaminergic cell fate.•Changes in dopaminergic system could precede the manifestation of HD symptoms. Hyperactivity of the dopaminergic pathway is thought to contribute to clinical symptoms in the early stages of Huntington’s disease (HD). It is suggested to be result of a reduced dopaminergic inhibition by degeneration of medium spiny neurons in the striatum. Previously, we have shown that the number of dopaminergic cells is increased in the dorsal raphe nucleus (DRN) of HD patients and transgenic HD (tgHD) rats during the manifestation phase of the disease; as well as in the substantia nigra pars compacta (SNc) and ventral tegmental area (VTA) of tgHD rats. To address whether these changes are secondary to neurodegeneration or take place in the pre-manifest phase of the disease, we examined the expression of genes controlling neuronal cell fate and genes that define dopaminergic cell phenotype. In the SNc-VTA of tgHD rats, Msx1 was upregulated, which correlated with an altered expression of transcription factors Zbtb16 and Tcf12. Zbtb16 was upregulated in the DRN and it was the only gene that showed a correlated expression in the tgHD rats between SNc-VTA and DRN. Zbtb16 may be a candidate for regionally tuning its cell populations, resulting in the increase in dopaminergic cells observed in our previous studies. Here, we demonstrated an altered expression of genes related to dopaminergic cell fate regulation in the brainstem of 6 months-old tgHD rats. This suggests that changes in dopaminergic system in HD precede the manifestation of clinical symptoms, contradicting the theory that hyperdopaminergic status in HD is a consequence of neurodegeneration in the striatum.