Abstract
INTRODUCTION
It is unclear how early neuronal deficits occur in tauopathies, if these are associated with changes in neuronal network activity, and if they can be alleviated with therapies.
METHODS
To address this, we performed in vivo two-photon Ca2+ imaging in tauopathy mice at 6 versus 12 months, compared to controls, and treated the younger animals with a tau antibody.
RESULTS
Neuronal function was impaired at 6 months but did not deteriorate further at 12 months, presumably because cortical tau burden was comparable at these ages. At 6 months, neurons were mostly hypoactive, with enhanced neuronal synchrony, and had dysregulated responses to stimulus. Ex vivo, electrophysiology revealed altered synaptic transmission and enhanced excitability of motor cortical neurons, which likely explains the altered network activity. Acute tau antibody treatment reduced pathological tau and gliosis and partially restored neuronal function.
DISCUSSION
Tauopathies are associated with early neuronal deficits that can be attenuated with tau antibody therapy.
Highlights
Neuronal hypofunction in awake and behaving mice in early stages of tauopathy.
Altered network activity disrupted local circuitry engagement in tauopathy mice.
Enhanced neuronal excitability and altered synaptic transmission in tauopathy mice.
Tau antibody acutely reduced soluble phospho-tau and improved neuronal function.
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This post is Copyright: Changyi Ji,
Xiaofeng Yang,
Mohamed Eleish,
Yixiang Jiang,
Amber M. Tetlow,
Soomin C. Song,
Alejandro Martín‐Ávila,
Qian Wu,
Yanmei Zhou,
Wenbiao Gan,
Yan Lin,
Einar M. Sigurdsson | October 6, 2024