Exploration of Neuroprotective Therapy

Table 1. Analysis of m/hSnca and m/Snca probe distribution in serial brain sections of Thy1-h[A30P]αSyn and Thy1-h[wt]αSyn mouse lines. Results obtained in FISH; transgenic mice compared to control mice. The mSnca probe represents endogenous, mouse-selective Snca mRNA; the m/hSnca probe represents both mouse and human Snca CDS [thus revealing both endogenous (mouse) and transgenic (human) Snca mRNA] (Figure 1 for details). By comparing the labeling results obtained in FISH analysis in which the two Snca probes were implemented in control and transgenic mice for each transgenic mouse line, the same patterns are observed with the m/hSnca probe in control mice and the mSnca probe in both control and transgenic mice, while detection beyond this, as identified using the h/mSnca probe in transgenic mice, identifies transcriptional effects induced by the transgenic construct in transgenic mice

Regions	m/hSnca		mSnca		m/hSnca		mSnca
Regions	Control	Thy1-h[A30P]αSyn	Control	Thy1-h[A30P]αSyn	Control	Thy1-h[wt]αSyn	Control	Thy1-h[wt]αSyn
Anterior olfactory area	Yes	↑	Yes	Yes	Yes	↑	Yes	Yes
Granule cell layer of the olfactory bulb	Yes	Same	Yes	Yes	No	Yes	NA	NA
Mitral cell layer of the olfactory bulb	Yes	↑	Yes	Yes	Yes	↑	Yes	Yes
Glomerular layer of the olfactory bulb	No	Yes	NA	NA	Yes	Same	Yes	Yes
Cortex (including all its divisions)	Yes	↑	Yes	Yes	Yes	↑	Yes	Yes
Tenia tecta	Yes	↑	Yes	Yes	Yes	↑	Yes	Yes
Endopiriform claustrum	Yes	↑	Yes	Yes	Yes	↑	Yes	Yes
Olfactory tubercle	Yes	↑	Yes	Yes	Yes	↑	Yes	Yes
Ventral pallidum	Yes	↑	Yes	Yes	Yes	↑	Yes	Yes
Ventral striatum	Yes	↑	Yes	Yes	Yes	↑	Yes	Yes
Dorsal striatum	Yes	Same	Yes	Yes	Yes	↑	Yes	Yes
Septal hippocampal nucleus	No	Yes	NA	NA	Yes	↑	Yes	Yes
Lateral septum	Yes	↑	Yes	Yes	Yes	↑	Yes	Yes
Medium septum	Yes	↑	Yes	Yes	Yes	↑	Yes	Yes
Nucleus of the vertical limb of the diagonal band	Yes	↑	Yes	Yes	Yes	↑	Yes	Yes
Lateral preoptic area	Yes	↑	Yes	Yes	Yes	↑	Yes	Yes
Nucleus of the horizontal limb of the diagonal band	Yes	↑	Yes	Yes	Yes	↑	Yes	Yes
Medio preoptic area	Yes	↑	Yes	Yes	Yes	↑	Yes	Yes
Medial forebrain bundle area	Yes	↑	Yes	Yes	Yes	↑	Yes	Yes
Bed nucleus of the stria terminalis	Yes	↑	Yes	Yes	Yes	↑	Yes	Yes
Paraventricular thalamic nucleus	Yes	↑	Yes	Yes	Yes	↑	Yes	Yes
Globus pallidus	Yes	↑	Yes	Yes	Yes	↑	Yes	Yes
Thalamus (not including intermediodorsal nucleus)	Yes	↑	Yes	Yes	Yes	↑	Yes	Yes
Intermediodorsal thalamic nucleus	Yes	↑	Yes	Yes	Yes	↑	Yes	Yes
Hypothalamus (not including ventromedial nucleus)	Yes	↑	Yes	Yes	Yes	↑	Yes	Yes
Ventromedial hypothalamic nucleus	Yes	↑	Yes	Yes	Yes	↑	Yes	Yes
Amygdala	Yes	↑	Yes	Yes	Yes	↑	Yes	Yes
Hippocampus	Yes	↑	Yes	Yes	Yes	↑	Yes	Yes
Lateral habenula	No	Yes	NA	NA	Yes	↑	Yes	Yes
Medial lateral habenula	Yes	Same	Yes	Yes	Yes	Same	Yes	Yes
Subthalamic nucleus	Yes	↑	Yes	Yes	Yes	↑	Yes	Yes
Zona incerta	Yes	↑	Yes	Yes	Yes	↑	Yes	Yes
Mammillary nucleus	Yes	↑	Yes	Yes	Yes	↑	Yes	Yes
Geniculate nucleus	Yes	↑	Yes	Yes	Yes	↑	Yes	Yes
Red nucleus	Yes	↑	Yes	Yes	Yes	↑	Yes	Yes
Reticular formation	Yes	↑	Yes	Yes	Yes	↑	Yes	Yes
Superior colliculus	Yes	↑	Yes	Yes	Yes	↑	Yes	Yes
Retro-mammillary nucleus	Yes	↑	Yes	Yes	Yes	↑	Yes	Yes
Posterior hypothalamic area	Yes	↑	Yes	Yes	Yes	↑	Yes	Yes
Anterior pretectal nucleus	Yes	↑	Yes	Yes	Yes	↑	Yes	Yes
Interstitial nucleus of Cajal	Yes	↑	Yes	Yes	Yes	↑	Yes	Yes
Substantia nigra pars reticulata	Yes	↑	Yes	Yes	Yes	↑	Yes	Yes
Ventral tegmental area	Yes	↑	Yes	Yes	Yes	↑	Yes	Yes
Substantia nigra pars compacta	Yes	↑	Yes	Yes	Yes	↑	Yes	Yes
Periaqueductal gray	Yes	↑	Yes	Yes	Yes	↑	Yes	Yes
Oculomotor nucleus	Yes	↑	Yes	Yes	Yes	↑	Yes	Yes
Pontine nucleus	Yes	↑	Yes	Yes	Yes	↑	Yes	Yes
Interpeduncular nucleus	No	Yes	NA	NA	No	Yes	NA	NA
Sub-brachial nucleus	No	Yes	NA	NA	Yes	↑	Yes	Yes
Retro-rubral field	Yes	↑	Yes	Yes	Yes	↑	Yes	Yes
Median raphe nucleus	Yes	↑	Yes	Yes	Yes	↑	Yes	Yes
Dorsal raphe nucleus	Yes	↑	Yes	Yes	Yes	↑	Yes	Yes

Return to article view

Yes: detection of labeling; ↑: increased detection as compared to control mice; Same: same detection as in control mice (i.e. no difference transgene vs. control); NA: not applicable due to lack of detection in both control and transgenic mice; No: no detection of labeling in control mice

Supplementary materials

The supplementary material for this article is available at: https://www.explorationpub.com/uploads/Article/file/100453_sup_1.pdf.

Declarations

Acknowledgments

We thank Professor Philipp J. Kahle, Hertie Institute for Clinical Brain Research, and Professor Eliezer Masliah, National Institute of Aging, for generously providing the Thy1-h[A30P]αSyn and Thy1-h[wt]αSyn transgenic mouse lines, respectively.

Author contributions

BV: Formal Analysis, Investigation, Visualization, Validation, Writing—original draft, Writing—review & editing. SD: Formal Analysis, Investigation, Visualization, Validation. SEL and ER: Investigation. MI: Investigation, Writing—review & editing. ÅWM: Conceptualization, Formal Analysis, Investigation, Visualization, Writing—original draft, Writing—review & editing, Project administration, Resources, Supervision.

Conflicts of interest

SD is the owner of Oramacell, Paris, France. All other authors declare no conflict of interest.

Ethical approval

This study “Aldh1a1 and additional markers of dopamine cell heterogeneity in substantia nigra and ventral tegmental area identified as preserved in two transgenic α-synuclein mouse models of neurodegenerative disease” was approved by the local Uppsala Animal Ethical Committee. Ethical approval number: 5.8.18-08038/2018; 2018-06-21; Head investigator: Martin Ingelsson (Title: “Utveckling av nya behandlingsstrategier för Parkinsons sjukdom/Lewykroppsdemens och Alzheimers sjukdom”). All procedures were in accordance with Swedish regulations and European Union legislation.

Consent to participate

Not applicable.

Consent to publication

Not applicable.

Availability of data and materials

Protocols for this study are published and included here, while data is shared by authors upon request. No specific material is relevant to this study; all can be purchased.

Funding

This work was supported by grants to ÅWM from the Vetenskapsrådet [2021-04975], Hjärnfonden [FO2022-0284], Parkinsonfonden [1232/19], Hållsten Research Foundation (Grant name: Motion & Emotion), Foundation for Zoological Research, Åhlén Foundation [203081] and to BV from Foundation for Zoological Research. The funding bodies have had no role in study design, in the collection, analysis, and interpretation of the data; in the writing of the report; and in the decision to submit the paper for publication.

Copyright

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