# Oral Supplementation With a Bovine Thymus Extract Reduces Neuronal Excitability in Aging Mice

## TL;DR

Giving aging mice a bovine thymus extract boosts GABA-related proteins and lowers brain excitability, which could help with age-related brain issues.

## Contribution

This study shows that bovine thymus extract enhances GABAergic neurotransmission and reduces neuronal excitability in aging mice.

## Key findings

- TNF supplementation increased GAD65 and GAD67 expression in the brains of aging mice.
- High-dose TNF reduced cortical excitability as shown by EEG and power spectral density analysis.
- TNF treatment improved locomotor activity in aging mice in a dose-dependent manner.

## Abstract

Gamma‐aminobutyric acid (GABA) is the primary inhibitory neurotransmitter in the central nervous system (CNS). Many aspects of GABAergic neurotransmission, including the densities of GABAergic neurons, the synthesis of GABA and its interaction with the respective receptors, are believed to be altered during aging, contributing to increased neuronal excitability seen in multiple neurodegenerative conditions, such as dementias, Alzheimer's disease, and traumatic brain injury (TBI). Oral administration of a nuclear fraction extract of the bovine thymus gland (thymus nuclear fraction—TNF) to rats was recently reported to improve their functional recovery from controlled cortical impact (CCI)—an animal model of TBI. Given that individual thymic peptides and mixed thymus fractions were also found to have broad neuroprotective effects and anti‐neuroinflammatory activity, we sought to investigate the impact of TNF on GABAergic neurotransmission in the aging mouse brain. Using biochemical investigation, electrophysiological recordings, obtained using electroencephalography (EEG), and power spectral density analysis, we evaluated GABAergic protein expression and cortical neuronal activity in aged control mice and in mice supplemented with a low dose (LD) or a high dose of TNF for 14 weeks. We uncovered increased expression of two isoforms of glutamic acid decarboxylase, GAD65 and GAD67, and increased levels of β2/β3 subunits of GABAA receptor in the brains of TNF‐supplemented mice compared to the control group, suggesting possible enhancement of inhibitory neurotransmission. Decreased neuronal excitability, evidenced by reduced EEG amplitudes, power spectral densities, and peak amplitudes of high‐frequency cortical oscillations, further confirmed a dose‐dependent attenuation of neuronal excitability by TNF. Our results suggest that TNF supplementation may have the potential to mitigate age‐related alterations in GABAergic neurotransmission, thereby modulating neuronal excitability.

Oral supplementation of aging mice with a nuclear fraction extract of bovine thymus (TNF) leads to significant increases in GAD65, GAD67, and β2/β3 subunits of the GABAA receptor, more so with high dose (HD) TNF treatment compared to low dose (LD) and control condition. Increases in GABAergic protein expression are accompanied by better locomotor activity in HD TNF‐supplemented animals. Supplementation with TNF extract reduces cortical excitability in a dose‐dependent manner. Created in https://BioRender.com.