Whole-Brain Afferent Inputs to the Caudate Nucleus, Putamen, and Accumbens Nucleus in the Tree Shrew Striatum

Ni, Rong-Jun; Shu, Yu-Mian; Li, Tao; Zhou, Jiang‐Ning

doi:10.3389/fnana.2021.763298

Cited by 4 publications

(4 citation statements)

References 140 publications

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“…In contrast, many well-defined and TH-positive dopaminergic neurons were present in the healthy side of the substantia nigra. The somas of these neurons were mostly spindle-shaped, with clearly visible brown-stained processes and blue-centered nuclei (Figure 7E), similar to the recently published study on midbrain anatomy and cellular morphology in normal tree shrews (Ni et al, 2021).…”

Section: Tree Shrews Exhibited Marked Nigral Dopaminergic Neuronal Lo...supporting

confidence: 89%

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New tree shrew Parkinson’s model: a cost-effective alternative to monkey models

Li,

Mei,

Nie

et al. 2023

Preprint

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The surge in demand for experimental monkeys has led to a rapid increase in their associated costs. Consequently, there is a growing need for the development of a cost-effective model for Parkinson's disease (PD) that exhibits all core clinical and pathological phenotypes of PD. Evolutionarily, tree shrews (Tupaia belangeri) are much closer to primates in comparison to rodents and share more similar PD-related brain structures and movement ability with monkeys. As such, tree shrews represent an ideal small animal species for modeling PD. To develop a tree shrew PD model, we used the 1-Methyl-4-phenylpyridinium (MPP+) metabolite, derived from the well-established PD modeling drug 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), to induce lesions in the dopaminergic neurons of the unilateral substantia nigra. After determining the optimal modeling dosage, the tree shrews consistently exhibited and maintained all classic clinical manifestations of PD for a 5-month period. The symptoms closely resembled the ones observed in PD monkeys and included bradykinesia, rest tremor, postural instability, and apomorphine-induced rotations, a classic phenotype of unilateral PD models. Immunostaining showed a significant loss of dopaminergic neurons (approximately 95%) in the substantia nigra on the lesioned side of the brain, a crucial pathological marker of PD. Further cytomorphological analysis revealed that the size of nigral dopaminergic neurons in tree shrews exceeded that of rodents and more closely approximated that of macaques. Based on the principle that structure determines function, the morphological similarity between tree shrews and monkeys may be an important structural basis for the manifestation of the highly similar phenotypes between monkey and tree shrew PD models. Collectively, this study successfully developed a PD model in a small animal species that faithfully recapitulated the classical clinical symptoms and key pathological indicators of PD monkeys. In addition to the well-recognized monkey models, the tree shrew model provides a novel avenue for the evaluation of PD treatments and underlying mechanisms.

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Section: Tree Shrews Exhibited Marked Nigral Dopaminergic Neuronal Lo...supporting

confidence: 89%

“…The copyright holder for this preprint this version posted September 5, 2023. ; https://doi.org/10.1101/2023.09.01.555918 doi: bioRxiv preprint (Figure 7E), similar to the recently published study on midbrain anatomy and cellular morphology in normal tree shrews (Ni et al, 2021).…”

Section: Tree Shrews Exhibited Marked Nigral Dopaminergic Neuronal Lo...supporting

confidence: 86%

New tree shrew Parkinson’s model: a cost-effective alternative to monkey models

Li,

Mei,

Nie

et al. 2023

Preprint

View full text Add to dashboard Cite

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“…KEGG pathways showed that the differentially upregulated genes in Pu are related to the cAMP signaling pathway, including genes such as ADCY8 (GPCR), CRHR1, GRIA3, GRIN3A, PDE4B, PLCE1, and RYR2. Thus, these data suggest that there is an overexpression of AMPA and NMDA receptor subunits (related to Ca2+ and Na+ flux) in Pu compared to CN via cAMP/GPCRs activation, which could lead to enhanced long-term potentiation and higher synaptic plasticity in Pu vs. CN and explain why CN and Pu inputs and functionalities are not equivalent 31 .…”

Section: Interneuron Populations Exhibit Region-based Differences Wit...mentioning

confidence: 89%

Interneuron diversity in the human dorsal striatum

Garma

Harder

Barba-Reyes

et al. 2023

Preprint

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Deciphering the striatal interneuron diversity is key to understanding the basal ganglia circuit and to untangle the complex neurological and psychiatric diseases affecting this brain structure. We performed single-nucleus RNA-sequencing (snRNA-seq) of postmortem human caudate nucleus (CN) and putamen (Pu) samples to elucidate the diversity and abundance of interneuron populations and their transcriptional structure in the human dorsal striatum. We propose a new taxonomy of striatal interneurons with eight main classes. We provide specific markers for all subclasses and validated some of them with quantitative in situ fluorescence hybridization, such as a novel PTHLH-expressing population that exhibits different abundance and gene expression between CN and Pu. For the most abundant interneuron populations in human striatum, PTHLH and TAC3, we found matching known mouse interneuron populations based on key functional genes such as ion channels and synaptic receptors. Remarkably, human TAC3 and mouse Th populations share important similarities including the expression of the neuropeptide tachykinin 3. Finally, we were able to integrate our dataset with several prior smaller human striatal snRNA-seq studies, thus supporting the generalizability of this new harmonized taxonomy.

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“…KEGG pathways showed that the differentially upregulated genes in Pu are related to the cAMP signaling pathway, including genes such as ADCY8 (GPCR), CRHR1, GRIA3, GRIN3A, PDE4B, PLCE1, and RYR2. Thus, these data suggest that there is an over-expression of AMPA and NMDA receptor subunits (related to Ca2 + and Na + ux) in Pu compared to CN via cAMP/GPCRs activation, which could lead to enhanced long-term potentiation and higher synaptic plasticity in Pu vs. CN and explain why CN and Pu inputs and functionalities are not equivalent 31 .…”

Section: Validation Of Interneuron Taxonomy With Uorescent In Situ Hy...mentioning

confidence: 87%

Interneuron diversity in the human dorsal striatum

Garma

Harder

Barba-Reyes

et al. 2023

Preprint

View full text Add to dashboard Cite

Deciphering the striatal interneuron diversity is key to understanding the basal ganglia circuit and to untangle the complex neurological and psychiatric diseases affecting this brain structure. We performed snRNA-seq of postmortem human caudate nucleus and putamen samples to elucidate the diversity and abundance of interneuron populations and their transcriptional structure in the human dorsal striatum. We propose a new taxonomy of striatal interneurons with eight main classes and fourteen subclasses and provide their specific markers and some quantitative FISH validation, particularly for a novel PTHLH-expressing population. For the most abundant populations, PTHLH and TAC3, we found matching known mouse interneuron populations based on key functional genes such as ion channels and synaptic receptors. Remarkably, human TAC3 and mouse Th populations share important similarities including the expression of the neuropeptide tachykinin 3. Finally, we were able to integrate other published datasets supporting the generalizability of this new harmonized taxonomy.

show abstract

Whole-Brain Afferent Inputs to the Caudate Nucleus, Putamen, and Accumbens Nucleus in the Tree Shrew Striatum

Cited by 4 publications

References 140 publications

New tree shrew Parkinson’s model: a cost-effective alternative to monkey models

New tree shrew Parkinson’s model: a cost-effective alternative to monkey models

Interneuron diversity in the human dorsal striatum

Interneuron diversity in the human dorsal striatum

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