Biomedical subjects

Dirk Jones

Publications and source records attributed to Dirk Jones.

3 recordsLinked to original sources

PubMed2006

Neurodegeneration produced by rotenone in the mouse retina: a potential model to investigate environmental pesticide contributions to neurodegenerative diseases.

Rotenone is a widely used pesticide and fish toxin that inhibits complex I of the mitochondrial respiratory chain. Complex I dysfunction is linked to the degeneration of retinal ganglion cells in Leber's optic neuropathy. To study the association between environmental mitochondrial toxin exposure and neurodegeneration, mice were intravitreally microinjected with rotenone in one eye and with the vehicle dimethyl sulfoxide in the contralateral eye, as a within-subject control. The retinal ganglion cell layer (GCL) of eyes injected with rotenone became significantly thinner than that of the control eyes after 24 h, but not as early as 0.5 h. This reduction was observed using complex I histochemistry and with Nissl staining of cell bodies. After 24 h, retinal nerve fiber layer thickness was reduced by 89% and the number of GCL cells was reduced by 21% in rotenone-treated eyes. Cellular morphometric data (soma area, perimeter, and diameter) did not show overall differences, but there was a preferential reduction in the proportion of larger cells. Therefore, the reduction in GCL thickness 24 h after rotenone microinjection could be accounted for by cell loss and nerve fiber shrinkage, but not by overall soma size change. Rotenone-induced degeneration of the ganglion cell layer may be used as a convenient way to (1) evaluate mechanisms and treatments for the neurodegeneration produced by mitochondrial dysfunction and (2) investigate environmental pesticide contributions to neurodegenerative diseases.

Animals↗

PubMed2003

Metabolic mapping of mouse brain activity after extinction of a conditioned emotional response.

Metabolic mapping with fluorodeoxyglucose (FDG), a radiolabeled glucose analog, was used to assess regional activity changes in the mouse brain that result from extinction of a conditioned emotional response (CER). In the extinction group, Pavlovian tone-foot shock conditioning, followed by repeated tone-alone presentations, resulted in the reduction of the CER (freezing behavior). A second group underwent CER acquisition alone (nonextinction group), and a third group showed no CER after pseudorandom training. Then mice were injected with FDG, and tone-evoked brain activity was mapped. In the auditory system, increased activity resulted from the associative effects of acquisition training. Effects common to extinction and nonextinction groups, presumably reflecting the tone-foot shock association independently of CER expression, were found in the medial geniculate, hippocampus, and subiculum. In the extinction group, a major finding was the elevated activity in prefrontal cortex regions. In addition, brain-behavior correlations between FDG uptake and freezing behavior confirmed that subjects with higher prefrontal activity were more successful at inhibiting the CER. Interregional activity correlations showed extensive functional coupling across large-scale networks in the extinction group. The increased activity of the prefrontal cortex and its negative interactions with other regions within the extinction group suggest a functional network inhibiting the CER composed of prefrontal cortex, medial thalamus, auditory, and hippocampal regions. This is the first time that such a functional network resulting from Pavlovian extinction has been demonstrated, and it supports Pavlov's original hypothesis of extinction as the formation of cortical inhibitory circuits, rather than unlearning or reversal of the acquisition process.

Acoustic Stimulation↗

PubMed2002

Mouse model of optic neuropathy caused by mitochondrial complex I dysfunction.

We developed a mouse model of optic neuropathy caused by mitochondrial complex I dysfunction by intravitreal administration of rotenone, a complex I inhibitor, in CBA/J mice. Retinal thickness was measured in sections stained histochemically for complex I enzymatic activity. The retinal ganglion cell layer of eyes injected with rotenone was significantly thinner than that of the control eyes injected with the vehicle dimethyl sulfoxide at 1, 24, and 48-h survival time groups. The largest reduction was 43% at 24-h post-injection. This effect is consistent with the degeneration of retinal ganglion cells in Leber's hereditary optic neuropathy. This is the first animal model of optic neuropathy caused by mitochondrial dysfunction, and it could be used as a quick and convenient way to test new treatments for mitochondrial neurodegenerative diseases.

Animals↗