2016
DOI: 10.1016/j.nbd.2015.10.021
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Severely impaired hippocampal neurogenesis associates with an early serotonergic deficit in a BAC α-synuclein transgenic rat model of Parkinson's disease

Abstract: Parkinson's disease (PD) is a multisystem disorder, involving several monoaminergic neurotransmitter systems resulting in a broad range of motor and non-motor symptoms. Pathological hallmarks of PD are the loss of dopaminergic neurons and the accumulation of alpha-synuclein, however also being present in the serotonergic raphe nuclei early in the disease course. The dysfunction of the serotonergic system projecting to the hippocampus might contribute to early non-motor symptoms such as anxiety and depression. … Show more

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Cited by 82 publications
(69 citation statements)
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References 79 publications
(112 reference statements)
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“…Aforementioned BAC transgenic rats (published by Nuber et al, 2013) additionally display severe impairment of hippocampal neurogenesis, a feature strongly associated with early behavioral phenotypes like depression and anxiety at 4 months of age, even prior to the onset of a motor phenotype (Kohl et al, 2016). Impaired hippocampal neurogenesis was accompanied by a profoundly reduced serotonergic innervation of the hippocampal dentate gyrus (DG; Kohl et al, 2016).…”
Section: Axonal Degeneration In Murine Pd Modelsmentioning
confidence: 99%
See 1 more Smart Citation
“…Aforementioned BAC transgenic rats (published by Nuber et al, 2013) additionally display severe impairment of hippocampal neurogenesis, a feature strongly associated with early behavioral phenotypes like depression and anxiety at 4 months of age, even prior to the onset of a motor phenotype (Kohl et al, 2016). Impaired hippocampal neurogenesis was accompanied by a profoundly reduced serotonergic innervation of the hippocampal dentate gyrus (DG; Kohl et al, 2016).…”
Section: Axonal Degeneration In Murine Pd Modelsmentioning
confidence: 99%
“…Impaired hippocampal neurogenesis was accompanied by a profoundly reduced serotonergic innervation of the hippocampal dentate gyrus (DG; Kohl et al, 2016). Furthermore, 5-HT receptor expression was altered and 5-HT levels were significantly reduced in the hippocampal DG and CA3 region of transgenic animals, strongly indicating an early dysfunction of serotonergic terminals.…”
Section: Axonal Degeneration In Murine Pd Modelsmentioning
confidence: 99%
“…Evidence of abnormal adult hippocampal neurogenesis (AHN) in postmortem PD brain and animal models of PD has led to the suggestion that cognitive and affective symptoms of PD may, in part, be a result of defective AHN (13, 14). In support of this notion, it has been shown that α‐synuclein disrupts AHN, which is associated with anxiety‐like behavior (17); however, studies that have investigated the effects of recessive PD gene mutations on adult neurogenesis are lacking, although recessive PD genes safeguard mitochondrial integrity (18) and mitochondrial network adaptations are critical for the differentiation of newborn hippocampal neurons (10). Here, we characterized AHN in PTEN‐induced kinase 1 (PINK1)–deficient mice.…”
mentioning
confidence: 99%
“…These rats also develop aggregates of insoluble proteinase K‐resistant α‐synuclein and significant nonmotor behavioral abnormalities including impaired odor discrimination, and changes in novelty‐seeking behavior before onset of the progressive motor deficits . Subsequent studies of the same line of BAC transgenic rats overexpressing wild‐type human α‐synuclein revealed significantly reduced serotonin levels in the hippocampus, with decreased hippocampal serotonergic fibers and unchanged raphe serotonergic neurons . These abnormalities occurred together with α‐synuclein aggregation and anxiety‐like behavior, as measured by reduced exploration and feeding.…”
Section: Genetic Rat Models Of Pdmentioning
confidence: 98%