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Striatal responses to partial dopaminergic lesion: evidence for compensatory sprouting.

ABSTRACT: Dopaminergic lesions result in the acute loss of striatal dopamine content, the loss of tyrosine hydroxylase-immunoreactive fibers, upregulation of preproenkephalin mRNA expression, and compensatory changes in the synthesis and metabolism of dopamine. Despite the severe loss of fine tyrosine hydroxylase-immunoreactive fibers, larger fibers persist. We found that some tyrosine hydroxylase fiber types increase their branching and become thicker after partial lesion. To determine whether the remaining tyrosine hydroxylase fibers were degenerative or part of a compensatory response, we morphologically characterized striatal tyrosine hydroxylase fibers and compared them to silver-stained degenerative structures. Branched and large tyrosine hydroxylase fiber types were nondegenerative. Furthermore, normal preproenkephalin mRNA expression was maintained despite severe overall loss of tyrosine hydroxylase fibers in striatal regions with abundant branching, whereas preproenkephalin mRNA expression increased in severely depleted regions that lacked branched fibers, indicating that branching or sprouting was involved in the compensation for dopamine depletion and the maintenance of normal preproenkephalin expression. In support of compensatory sprouting by tyrosine hydroxylase fibers, mRNA for growth associated protein-43 was upregulated in dopaminergic midbrain cells. We conclude that an important compensatory response to partial dopaminergic depletion is the formation of new branches or sprouting.

SUBMITTER: Song DD

PROVIDER: S-EPMC6772281 | biostudies-literature | 2000 Jul

REPOSITORIES: biostudies-literature

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Striatal responses to partial dopaminergic lesion: evidence for compensatory sprouting.

Song D D DD Haber S N SN

The Journal of neuroscience : the official journal of the Society for Neuroscience 20000701 13

Dopaminergic lesions result in the acute loss of striatal dopamine content, the loss of tyrosine hydroxylase-immunoreactive fibers, upregulation of preproenkephalin mRNA expression, and compensatory changes in the synthesis and metabolism of dopamine. Despite the severe loss of fine tyrosine hydroxylase-immunoreactive fibers, larger fibers persist. We found that some tyrosine hydroxylase fiber types increase their branching and become thicker after partial lesion. To determine whether the remain ...[more]

PMID: 10864967

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Project description:Cystectomy is the removal of all or part of the urinary bladder. It has been observed that there is significant regrowth of the bladder after partial cystectomy and this has been proposed to be through regeneration of the organ. Regrowth of tissue in mammals has been proposed to involve compensatory mechanisms that share many characteristics of true regeneration, like the growth of specialized structures such as blood vessels or nerves. However, the overall structure of the normal organ is not achieved. Here we tested if bladder growth after subtotal cystectomy (STC, removal of 50% of the bladder) was compensatory or regenerative. To do this we subjected adult female mouse bladders to STC and assessed regrowth using several established cellular parameters including histological, gene expression, cytokine accumulation and cell proliferation studies. Bladder function was analyzed using cystometry and the voiding stain on paper (VSOP) technique. We found that STC bladders were able to increase their ability to hold urine with the majority of volume restoration occurring within the first two weeks. Regenerating bladders had thinner walls with less mean muscle thickness, and they showed increased collagen deposition at the incision as well as throughout the bladder wall suggesting that fibrosis was occurring. Cell populations differed in their response to injury with urothelial regeneration complete by day 7, but stromal and detrusor muscle still incomplete after 8wks. Cells incorporated EdU when administered at the time of surgery and tracing of EdU positive cells over time indicated that many newborn cells originate at the incision and move mediolaterally. Basal urothelial cells and bladder mesenchymal stem cells but not smooth muscle cells significantly incorporated EdU after STC. Since anti-inflammatory cytokines play a role in regeneration, we analyzed expressed cytokines and found that no anti-inflammatory cytokines were present in the bladder 1wk after STC. Our findings suggest that bladder regrowth after cystectomy is compensatory and functions to increase the volume that the bladder can hold. This finding sets the stage for understanding how the bladder responds to cystectomy and how this can be improved in patients after suffering bladder injury.

Project description:ObjectiveMajor depressive disorder is characterized by reduced reward-related striatal activation and dysfunctional reward learning, putatively reflecting decreased dopaminergic signaling. The goal of this study was to test whether a pharmacological challenge designed to facilitate dopaminergic transmission can enhance striatal responses to reward and improve reward learning in depressed individuals.MethodIn a double-blind placebo-controlled design, 46 unmedicated depressed participants and 43 healthy control participants were randomly assigned to receive either placebo or a single low dose (50 mg) of the D2/D3 receptor antagonist amisulpride, which is believed to increase dopamine signaling through presynaptic autoreceptor blockade. To investigate the effects of increased dopaminergic transmission on reward-related striatal function and behavior, a monetary incentive delay task (in conjunction with functional MRI) and a probabilistic reward learning task were administered at absorption peaks of amisulpride.ResultsDepressed participants selected previously rewarded stimuli less frequently than did control participants, indicating reduced reward learning, but this effect was not modulated by amisulpride. Relative to depressed participants receiving placebo (and control participants receiving amisulpride), depressed participants receiving amisulpride exhibited increased striatal activation and potentiated corticostriatal functional connectivity between the nucleus accumbens and the midcingulate cortex in response to monetary rewards. Stronger corticostriatal connectivity in response to rewards predicted better reward learning among depressed individuals receiving amisulpride as well as among control participants receiving placebo.ConclusionsAcute enhancement of dopaminergic transmission potentiated reward-related striatal activation and corticostriatal functional connectivity in depressed individuals but had no behavioral effects. Taken together, the results suggest that targeted pharmacological treatments may normalize neural correlates of reward processing in depression; despite such acute effects on neural function, behavioral modification may require more chronic exposure. This is consistent with previous reports that antidepressant effects of amisulpride in depression emerged after sustained administration.

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Striatal responses to partial dopaminergic lesion: evidence for compensatory sprouting.

Publications

Striatal responses to partial dopaminergic lesion: evidence for compensatory sprouting.

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