RT Journal Article
SR Electronic
T1 A partial reduction of Drp1 enhances mitophagy, autophagy, mitochondrial biogenesis, dendritic spines and synaptic activity in a transgenic Tau mouse model of Alzheimer disease
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.10.07.463521
DO 10.1101/2021.10.07.463521
A1 Ramesh Kandimalla
A1 Maria Manczak
A1 Jangampalli Adi Pradeepkiran
A1 P. Hemachandra Reddy
YR 2021
UL http://biorxiv.org/content/early/2021/10/09/2021.10.07.463521.abstract
AB The purpose of our study is to understand the impact of a partial dynamin-related protein 1 (Drp1) on cognitive behavior, mitophagy/autophagy, mitochondrial and synaptic activities in transgenic Tau mice in Alzheimer’s disease (AD). Our lab reported increased levels of Aβ and P-Tau, and abnormal interactions between Aβ and Drp1, P-Tau and Drp1 induced increased mitochondrial fragmentation and reduced fusion and synaptic activities in AD. These abnormal interactions, result in the proliferation of dysfunctional mitochondria in AD neurons. Recent research on mitochondria revealed that fission protein Drp1 is largely implicated in mitochondrial dynamics in AD. To determine the impact of reduced Drp1 in AD, we recently crossed transgenic Tau mice with Drp1 heterozygote knockout (Drp1+/-) mice and generated double mutant (Drp1+/- X Tau) mice. In the current study, we assessed cognitive behavior, mRNA and protein levels of mitophagy, autophagy, mitochondrial biogenesis, dynamics and synaptic genes, mitochondrial morphology & mitochondrial function, dendritic spines in Tau mice relative to double mutant mice. When compared to Tau mice, double mutant mice did better on Morris Maze (reduced latency to find hidden platform, increased swimming speed and time spent on quadrant) and rotarod (stayed a longer period of time) tests. Both mRNA and proteins levels autophagy, mitophagy, mitochondrial biogenesis and synaptic proteins were increased in double mutant mice compared to Tau mice. Dendritic spines were significantly increased; mitochondrial number is reduced and length is increased in double mutant mice. Based on these observations, we conclude that reduced Drp1 is beneficial in a symptomatic-transgenic Tau mice.Competing Interest StatementThe authors have declared no competing interest.