Causal factors of psychiatric diseases are unclear, due to gene×environment interactions. Evaluation of consequences, after a dopamine-transporter (DAT) gene knock-out (DATKO), has enhanced understanding the pathological dynamics of several brain disorders, such as Attention-Deficit/Hyperactivity and Bipolar-Affective disorders. Recently, our attention has shifted to DAT hypo-functional (heterozygous, HET) rodents: HET dams display less maternal care and HET females display marked hypo-locomotion if cared by HET dams (Mariano et al., 2019). We assessed phenotypes of male DAT-heterozygous rats as a function of their parents: we compared “maternal” origin (MAT-HET, obtained by breeding KO-male rats with WT-female dams) to “mixed” origin (MIX-HET, obtained by classical breeding, both heterozygous parents) of the allele. MAT-HET subjects had significantly longer rhythms of daily locomotor activity than MIX-HET and WT-control subjects. Furthermore, acute methylphenidate (MPH: 0, 1, 2 mg/kg) revealed elevated threshold for locomotor stimulation in MAT-HETs, with no response to the lower dose. Finally, by Porsolt-Test, MAT-HETs showed enhanced escape-seeking (diving) with more transitions towards behavioral despair (floating). When comparing both MAT- and MIX-HET to WT-control rats, decreased levels of DAT and HDAC4 were evident in the ventral-striatum; moreover, with respect to MIX-HET subjects, MAT-HET ones displayed increased DAT density in dorsal-striatum. MAT-HET rats displayed region-specific changes in DAT expression, compared to “classical” MIX-HET subjects: greater DAT availability may elevate threshold for dopamine action. Further behavioral and epigenetic characterizations of MAT-HETs, together with deeper characterization of maternal roles, could help to explore parent-of-origin mechanisms for such a peculiar phenotype.

Cristiana, C., Anna, B., Annalisa, A., Lo Russo, S.L.M., Enrico, A., Carla, C., et al. (2020). Motor transitions’ peculiarity of heterozygous DAT rats when offspring of an unconventional KOxWT mating. NEUROSCIENCE [10.1016/j.neuroscience.2020.03.005].

Motor transitions’ peculiarity of heterozygous DAT rats when offspring of an unconventional KOxWT mating

Anna, Brancato;Carla, Cannizzaro;
2020-01-01

Abstract

Causal factors of psychiatric diseases are unclear, due to gene×environment interactions. Evaluation of consequences, after a dopamine-transporter (DAT) gene knock-out (DATKO), has enhanced understanding the pathological dynamics of several brain disorders, such as Attention-Deficit/Hyperactivity and Bipolar-Affective disorders. Recently, our attention has shifted to DAT hypo-functional (heterozygous, HET) rodents: HET dams display less maternal care and HET females display marked hypo-locomotion if cared by HET dams (Mariano et al., 2019). We assessed phenotypes of male DAT-heterozygous rats as a function of their parents: we compared “maternal” origin (MAT-HET, obtained by breeding KO-male rats with WT-female dams) to “mixed” origin (MIX-HET, obtained by classical breeding, both heterozygous parents) of the allele. MAT-HET subjects had significantly longer rhythms of daily locomotor activity than MIX-HET and WT-control subjects. Furthermore, acute methylphenidate (MPH: 0, 1, 2 mg/kg) revealed elevated threshold for locomotor stimulation in MAT-HETs, with no response to the lower dose. Finally, by Porsolt-Test, MAT-HETs showed enhanced escape-seeking (diving) with more transitions towards behavioral despair (floating). When comparing both MAT- and MIX-HET to WT-control rats, decreased levels of DAT and HDAC4 were evident in the ventral-striatum; moreover, with respect to MIX-HET subjects, MAT-HET ones displayed increased DAT density in dorsal-striatum. MAT-HET rats displayed region-specific changes in DAT expression, compared to “classical” MIX-HET subjects: greater DAT availability may elevate threshold for dopamine action. Further behavioral and epigenetic characterizations of MAT-HETs, together with deeper characterization of maternal roles, could help to explore parent-of-origin mechanisms for such a peculiar phenotype.
Settore BIO/14 - Farmacologia
Cristiana, C., Anna, B., Annalisa, A., Lo Russo, S.L.M., Enrico, A., Carla, C., et al. (2020). Motor transitions’ peculiarity of heterozygous DAT rats when offspring of an unconventional KOxWT mating. NEUROSCIENCE [10.1016/j.neuroscience.2020.03.005].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10447/402361
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