The BDNF Mimetic R-13 Attenuates TBI Pathogenesis Using TrkB-related Pathways and Bioenergetics

Overview

Journal Biochim Biophys Acta Mol Basis Dis

Publisher Elsevier

Specialties Biochemistry
Biophysics
Genetics
Molecular Biology

Date 2023 Jun 7

PMID 37286142

Authors

Pavan Thapak

Gregory Smith

Zhe Ying

Afshin Paydar

Neil Harris

Fernando Gomez-Pinilla

Affiliations

Soon will be listed here.

Abstract

Traumatic brain injury (TBI) is major neurological burden globally, and effective treatments are urgently needed. TBI is characterized by a reduction in energy metabolism and synaptic function that seems a primary cause of neuronal dysfunction. R13, a small drug and BDNF mimetic showed promising results in improving spatial memory and anxiety-like behavior after TBI. Additionally, R13 was found to counteract reductions in molecules associated with BDNF signaling (p-TrkB, p-PI3K, p-AKT), synaptic plasticity (GluR2, PSD95, Synapsin I) as well as bioenergetic components such as mitophagy (SOD, PGC-1α, PINK1, Parkin, BNIP3, and LC3) and real-time mitochondrial respiratory capacity. Behavioral and molecular changes were accompanied by adaptations in functional connectivity assessed using MRI. Results highlight the potential of R13 as a therapeutic agent for TBI and provide valuable insights into the molecular and functional changes associated with this condition.

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