Sperm RNAs in inheritance

Parkinson’s disease is the second most common neurodegenerative disease, which is described as the selective loss of dopaminergic neurons. In response to cellular stress, dysfunctional mitochondria produce ROS and other pro-death mediators to initiate cell death programs, such as apoptosis, necroptosis and cell death. Defects in mitophagy lead to a variety of mitochondrial diseases.

PGAM5 has also been reported as a genetic suppressor of PINK1 in Drosophila. We generated Pgam5 knockout (KO) mice from gene-targeted embryonic stem cells and have confirmed its KO efficiency. We examined mouse embryonic?broblasts (MEFs) by microscopy (TEM). KO MEFs contained an increased number of swollen bulbous mitochondria that lacked normal cristae and were?lled with debris.

PGAM5 is required for the stabilization of the mitophagy-inducing protein PINK1 on damaged mitochondria. Loss of PGAM5 disables PINK1-mediated mitophagy in vitro and leads to dopaminergic neurodegeneration and mild dopamine loss in vivo. Lent viral-mediated expression of GFP-tagged PGAM5 in KO MEFs rescued PINK1 indicating that PGAM5 accounted for PINK1 mitochondrial stabilization

We evaluated neurological function using behavioral tests on Pgam5 KO mice at 1 year of age. The behavioral phenotype of Pgam5 Ko mice reveals some, but not all Parkinson’s disease features.

PGAM5 is a regulator of mitophagy involved in mitochondrial turnover and a key player of DA neuron survival in vivo.

Individuals who have experienced trauma often have children that also display particular behavioral traits, such as depression and anxiety. This observation led researchers to believe that there may be more to the story than purely social explanations.

Epigenetic inheritance is the transmittance of information from one generation to the next that affects the traits of offspring without alteration of the primary structure of DNA. sncRNAs are potential mediators of gene-environment interactions that can relay signals from the environment to the genome and exert regulatory functions on gene activity. Besides sncRNAs are abundant in the mature sperm in mammals and may therefore convey transgenerational inheritance

Deep sequencing of purified sperm RNA identified several populations of short RNAs mapping to the mouse genome to a different degree and fidelity. Injection of sperm RNAs from traumatized males into fertilized wild-type oocytes reproduced the behavioral and metabolic alterations in the resulting offspring.

This work provides evidence for the idea that RNA-dependent processes contribute to the transmission of acquired traits in mammals. They underline the significance of sncRNAs in germ cells and highlight their sensitivity to early traumatic stress. The identification of several miRNAs and putative targets as mediators of these effects provide molecular markers of traumatic stress for potential use for the diagnostic of stress predisposition and stress-induced disorders in humans.

Numerologist Warda is hooked on OG-L002 fishing, collecting. And lastly her encouragement comes from socializing along with her companions.