Dataset Information

Analysis of human tau and age dependent changes in the synaptic and non-synaptic mitochondrial proteomes of the htau model of tauopathy

ABSTRACT: We investigated the effects of human tau on subcellular populations of the brain mitochondrial proteome in vivo using transgenic htau mice at ages preceding (5 months) and coinciding with (8 months) onset of tauopathy.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain

SUBMITTER: Kelly Stauch

LAB HEAD: Kelly L. Stauch, Ph.D.

PROVIDER: PXD030950 | Pride | 2022-02-28

REPOSITORIES: Pride

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			Action	DRS
	02Mar15_KS_Mito_NS_C3.wiff	Wiff
	02Mar15_KS_Mito_NS_C3.wiff.scan	Wiff
	02Mar15_KS_Mito_NS_H1.wiff	Wiff
	02Mar15_KS_Mito_NS_H1.wiff.scan	Wiff
	02Mar15_KS_Mito_NS_H2.wiff	Wiff

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Project description:Current human reproductive risk assessment methods rely on semen and serum hormone analyses, which are not easily comparable to the histopathological endpoints and mating studies used in animal testing. Because of these limitations, there is a need to develop universal evaluations that reliably reflect male reproductive function. We hypothesized that toxicant-induced testicular injury can be detected in sperm using mRNA transcripts as indicators of insult. To test this, we exposed adult male Fischer 344 rats to low doses of model testicular toxicants and classically characterized the testicular injury while simultaneously evaluating sperm mRNA transcripts from the same animals. Overall, this study aimed to: 1) identify sperm transcripts altered after exposure to the model testicular toxicant, 2,5-hexanedione (HD) using microarrays; 2) expand on the HD-induced transcript changes in a comprehensive time course experiment using qRT-PCR arrays; and 3) test these injury indicators after exposure to another model testicular toxicant, carbendazim (CBZ). Microarray analysis of HD-treated adult Fischer 344 rats identified 128 altered sperm mRNA transcripts when compared to control using linear models of microarray analysis (q < 0.05). All transcript alterations disappeared after 3 months of post-exposure recovery. In the time course experiment, time-dependent alterations were observed for 12 candidate transcripts selected from the microarray data based upon fold change and biological relevance, and 8 of these transcripts remained significantly altered after the 3-month recovery period (p < 0.05). In the last experiment, 8 candidate transcripts changed after exposure to CBZ (p < 0.05). The two testicular toxicants produced distinct molecular signatures with only 4 overlapping transcripts between them, each occurring in opposite directions. Overall, these results suggest that sperm mRNA transcripts are indicators of low dose toxicant-induced testicular injury in the rat. Rats were exposed to sub-chronic low doses of the Sertoli cell toxicant 2,5-hexanedione (HD) or water (control for HD) for 3 months. Some rats in each group underwent 3 months of post-exposure recovery.

Dataset Information

Analysis of human tau and age dependent changes in the synaptic and non-synaptic mitochondrial proteomes of the htau model of tauopathy

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