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. 2022 Sep;100(9):1747-1754.
doi: 10.1002/jnr.25067. Epub 2022 May 20.

NURR1-deficient mice have age- and sex-specific behavioral phenotypes

Francesca Montarolo  1   2   3 , Serena Martire  2 , Francesco Chiara  4 , Sarah Allegra  4 , Silvia De Francia  4 , Eriola Hoxha  1   5 , Filippo Tempia  1   5 , Marco Alfonso Capobianco  1   2 , Antonio Bertolotto  1
Affiliations

NURR1-deficient mice have age- and sex-specific behavioral phenotypes

Francesca Montarolo et al. J Neurosci Res. 2022 Sep.

Abstract

The transcription factor NURR1 is essential to the generation and maintenance of midbrain dopaminergic (mDA) neurons and its deregulation is involved in the development of dopamine (DA)-associated brain disorders, such as Parkinson's disease (PD). The old male NURR1 heterozygous knockout (NURR1-KO) mouse has been proposed as a model of PD due to its altered motor performance that was, however, not confirmed in a subsequent study. Based on these controversial results, we explored the effects of the NURR1 deficiency on locomotor activity, motor coordination, brain and plasma DA levels, blood pressure and heart rate of old mice, also focusing on the potential effect of sex. As a probable consequence of the role of NURR1 in DA pathway, we observed that the old NURR1-KO mouse is characterized by motor impairment, and increased brain DA level and heart rate, independently from sex. However, we also observed an alteration in spontaneous locomotor activity that only affects males. In conclusion, NURR1 deficiency triggers sex- and age-specific alterations of behavioral responses, of DA levels and cardiovascular abnormalities. Further studies in simplified systems will be necessary to dissect the mechanism underlying these observations.

Keywords: NURR1; Parkinson's disease; dopamine; locomotion; motor impairment; murine model.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

FIGURE 1
FIGURE 1
Behavioral phenotype of old NURR1‐KO mice. Both male (square) and female (circle) old WT (white) and NURR1‐KO (gray) mice were tested in the open field (OF) (a, b) and in the rotarod (c). Total distance traveled in the arena (a) and in the center of arena of the OF (b) are reported as centimeters (cm) and percentage of the distances traveled in the center versus the total distance, respectively. The latency to fall from the rotarod is reported as the mean of the third trials of each of the 3 days measured in seconds (s)(c). Line and bar indicate the median value and interquartile range. NURR1‐KO, NURR1 knockout; WT, wild‐type.
FIGURE 2
FIGURE 2
DA Level in brain and plasma of old NURR1‐KO mice. DA was measured in brain (a) and plasma (b) of both male (square) and female (circle) old WT (white) and NURR1‐KO (gray) mice. DA is reported as micrograms for milligram of brain tissue (μg/mg), and as micrograms for milliliter of plasma (μg/ml). Line and bar indicate the median value and interquartile range. NURR1‐KO, NURR1 knockout; WT, wild‐type.
FIGURE 3
FIGURE 3
Heart rate and systolic blood pressure of old NURR1‐KO mice. Heart rate (a) and systolic blood pressure (b) measurement of male (square) and female (circle) old WT (white) and NURR1‐KO (gray) mice are reported as number of pulse/min and millimeters of mercury (mmHg), respectively. Line and bar indicate the median value and interquartile range. NURR1‐KO, NURR1 knockout; WT, wild‐type.
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