Dataset Information

Olfactory dysfunction and neurotransmitter disturbance in olfactory bulb of transgenic mice expressing human A53T mutant ?-synuclein.

ABSTRACT: Parkinson disease is a multi-system neurodegenerative disease characterized by both motor and non-motor symptoms. Hyposmia is one of the early non-motor symptoms occurring in more than 90% of Parkinson disease cases, which can precede motor symptoms even several years. Up to now, the relationship between hyposmia and Parkinson disease remains elusive. Lack of proper animal models of hyposmia restricts the investigation. In this study we assessed olfactory function in Prp-A53T-?-synuclein transgenic (?SynA53T) mice which had been reported to show age-dependent motor impairments and intracytoplasmic inclusions. We also examined cholinergic and dopaminergic systems in olfactory bulb of ?SynA53T mice by immunofluorescent staining, enzyme linked immunosorbent assay and western blot. We found that compared to wild type littermates, ?SynA53T mice at 6 months or older displayed a deficit of odor discrimination and odor detection. No significant changes were found in olfactory memory and odor habituation. Furthermore compared to wildtype littermates, in olfactory bulb of ?SynA53T mice at 10 months old we detected a marked decrease of cholinergic neurons in mitral cell layer and a decrease of acetylcholinesterase activity, while dopaminergic neurons were found increased in glomerular layer, accompanied with an increase of tyrosine hydroxylase protein. Our studies indicate that ?SynA53T mice have olfactory dysfunction before motor deficits occur, and the cholinergic and dopaminergic disturbance might be responsible for the Parkinson disease-related olfactory dysfunction.

SUBMITTER: Zhang S

PROVIDER: S-EPMC4370499 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Olfactory dysfunction and neurotransmitter disturbance in olfactory bulb of transgenic mice expressing human A53T mutant α-synuclein.

Zhang Sufang S Xiao Qian Q Le Weidong W

PloS one 20150323 3

Parkinson disease is a multi-system neurodegenerative disease characterized by both motor and non-motor symptoms. Hyposmia is one of the early non-motor symptoms occurring in more than 90% of Parkinson disease cases, which can precede motor symptoms even several years. Up to now, the relationship between hyposmia and Parkinson disease remains elusive. Lack of proper animal models of hyposmia restricts the investigation. In this study we assessed olfactory function in Prp-A53T-α-synuclein transge ...[more]

PMID: 25799501

Similar Datasets

Project description:Abnormal intraneuronal accumulation of the presynaptic protein ?-synuclein (?-syn) is implicated in the etiology of dementia with Lewy bodies (DLB) and Parkinson's disease with dementia (PDD). Recent work revealed that mice expressing human ?-syn with the alanine-53-threonine (A53T) mutation have a similar phenotype to the human condition, exhibiting long-term potentiation deficits, learning and memory deficits, and inhibitory hippocampal remodeling, all of which were reversed by genetic ablation of microtubule-associated protein tau. Significantly, memory deficits were associated with histological signs of network hyperactivity/seizures. Electrophysiological abnormalities are often seen in parkinsonian dementias. Baseline electroencephalogram (EEG) slowing is used as a supportive diagnostic feature in DLB and PDD, and patients with these diseases may exhibit indicators of broad network dysfunction such as sleep dysregulation, myoclonus, and seizures. Given the translational significance, we examined whether human A53T ?-syn expressing mice exhibit endogenous-tau-dependent EEG abnormalities, as measured with epidural electrodes over the frontal and parietal cortices. Using template-based waveform sorting, we determined that A53T mice have significantly high numbers of epileptiform events as early as 3-4 months of age and throughout life, and this effect is markedly attenuated in the absence of tau. Epileptic myoclonus occurred in half of A53T mice and was markedly reduced by tau ablation. In spectral analysis, tau ablation partially reduced EEG slowing in 6-7 month transgenic mice. We found abnormal sleeping patterns in transgenic mice that were more pronounced in older groups, but did not find evidence that this was influenced by tau genotype. Together, these data support the notion that tau facilitates A53T ?-syn-induced hyperexcitability that both precedes and coincides with associated synaptic, cognitive, and behavioral effects. Tau also contributes to some aspects of EEG slowing in A53T mice. Importantly, our work supports tau-based approaches as an effective early intervention in ?-synucleinopathies to treat aberrant network activity.

Dataset Information

Olfactory dysfunction and neurotransmitter disturbance in olfactory bulb of transgenic mice expressing human A53T mutant ?-synuclein.

Publications

Olfactory dysfunction and neurotransmitter disturbance in olfactory bulb of transgenic mice expressing human A53T mutant α-synuclein.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets