Effect of methamphetamine on rat primary midbrain cells; mitochondrial biogenesis as a compensatory response.

Abstract:

:Methamphetamine (MA), neurotoxic drug of abuse, causes cell death in vitro and in vivo via several mechanisms such as mitochondrial dysfunction. In this study we evaluated the effect of MA on cell viability and mitochondrial biogenesis in primary midbrain culture. Primary mesencephalon cells prepared from E14.5 rat embryo were treated with 0.2-5 mM MA concentrations for 24, 48, and 72 h. Morphological changes of the cells were observed under light microscope. Cell viability and cell death following MA were assessed using MTT assay and immunocytochemistry. Gene expressions of mitochondrial biogenesis-involved factors (PGC1α, NRF1 and TFAM), and neuronal and glial markers were measured by qPCR. Low to moderate MA concentrations elevated cell viability in all time points, while higher concentrations and longer incubation times (48 and 72 h) decreased it. Sphered cell bodies and neurites degeneration were observed following exposure to high MA concentrations. MA at 5 mM concentration decreased the number of β3-tubulin-, TH-, GFAP- and Iba1-positive cells, and their corresponding mRNA levels; however, 1 mM MA reduced α-synuclein mRNA. Unexpectedly, gene expression of PGC1α, NRF1 and TFAM was increased in response to 5 mM MA, with no changes following 1 mM MA. The results indicated that MA effect on cell viability occurs in a dose-dependent manner. While moderate concentrations increased cell viability, the higher ones reduced it and caused cell death. Mitochondrial biogenesis activation, as a compensatory mechanism, did not prevent neuronal and glial cell death following high MA concentration.

journal_name

Neuroscience

journal_title

Neuroscience

authors

Valian N,Heravi M,Ahmadiani A,Dargahi L

doi

10.1016/j.neuroscience.2019.03.016

subject

Has Abstract

pub_date

2019-05-15 00:00:00

pages

278-289

eissn

0306-4522

issn

1873-7544

pii

S0306-4522(19)30167-8

journal_volume

406

pub_type

杂志文章