Drp1 is widely, yet heterogeneously, distributed in the mouse central nervous system

Abstract

Objectives: Drp1 is widely expressed in the mouse central nervous system and plays a role in inducing the mitochondrial fission process. Many diseases are associated with Drp1 and mitochondria. However, since the exact distribution of Drp1 has not been specifically observed, it is difficult to determine the impact of anti-Drp1 molecules on the human body. Clarifying the specific Drp1 distribution could be a good approach to targeted treatment or prognosis. Methods: We visualized the distribution of Drp1 in different brain regions and explicated the relationship between Drp1 and mitochondria. GAD67-GFP knock-in mice were utilized to detect the expression patterns of Drp1 in GABAergic neurons. We also further analyzed Drp1 expression in human malignant glioma tissue. Results: Drp1 was widely but heterogeneously distributed in the central nervous system. Further observation indicated that Drp1 was highly and heterogeneously expressed in inhibitory neurons. Under transmission electron microscopy, the distribution of Drp1 was higher in dendrites than other areas in neurons, and only a small amount of Drp1 was localized in mitochondria. In human malignant glioma, the fluorescence intensity of Drp1 increased from grade I-III, while grade IV showed a declining trend. Conclusion: In this study, we observed a wide heterogeneous distribution of Drp1 in the central nervous system, which might be related to the occurrence and development of neurologic disease. We hope that the relationship between Drp1 and mitochondria may will to therapeutic guidance in the clinic.

Visualizing an convergence of three mitochondrial molecule mRNAs for DRP1/MFN2/UCP4 on soma of cerebellar Purkinje cells by RNAscope

“…In mammalian cells, ssion/fusion events are mainly mediated by several large dynaminrelated GTPase proteins, including conserved dynamin-related GTPase (Drp1), conserved dynamin-related GTPase mitofusion 1 and 2 (Mfn1 and 2), and optic dominant atrophy 1 (Opa1). Our lab have published the data previously about the expression of Drp1 at high level on the soma of cerebellum Purkinje cells by the combination of immunohistochemistry and in situ hybridization on GAD67 (glutamic acid decarboxylase 67) -GFP (green uorescent protein) transgenic mice (Luo TT et al, 2020). The present ndings have con rmed the distribution pattern of Drp1 on Purkinje cells.…”

Visualizing a Convergence of Three Mitochondrial Molecule mRNAs for Drp1/Mfn2/Ucp4 on Soma of Cerebellar Purkinje Cells by RNAscope

“…In mammalian cells, ssion/fusion events are mainly mediated by several large dynaminrelated GTPase proteins, including conserved dynamin-related GTPase (Drp1), conserved dynamin-related GTPase mitofusion 1 and 2 (Mfn1 and 2), and optic dominant atrophy 1 (Opa1). Our lab have published the data previously about the expression of Drp1 at high level on the soma of cerebellum Purkinje cells by the combination of immunohistochemistry and in situ hybridization on GAD67 (glutamic acid decarboxylase 67) -GFP (green uorescent protein) transgenic mice [24]. The present ndings have con rmed the distribution pattern of Drp1 on Purkinje cells.…”

“…According to our previous report [24], we demonstrated that Drp1 was overexpressed in the cerebellum Purkinje layer, while Drp1 and GAD67 also colabeled well in this area. Drp1 and GAD67 colabeling was lower in other nuclei.…”

Targeted up-regulation of Drp1 in dorsal horn attenuates neuropathic pain hypersensitivity by increasing mitochondrial fission

“…Our previous study has shown that Drp1 is highly expressed at the spinal cord level [ 33 ]. And many studies have shown different NP contributed to the increased expression of Drp1 [ [34] , [35] , [36] , [37] , [38] , [39] , [40] , [41] , [42] ].…”

“…The dynamin family of large GTPases regulates mitochondrial membrane dynamics in all eukaryotes: Drp1 for fission, and mitofusins (Mfn1/2) and optic atrophy-1 (Opa1) for fusion [ [20] , [21] , [22] , [23] ]. Our own study has shown that Drp1 is distributed all over the whole nervous system, especially high at the spinal cord level [ 33 ]. In different NP model, Drp1 expression or its phosphorylated state is reported to either increase or decrease.…”