Synapse. 2021 Jun;75(6):e22193. doi: 10.1002/syn.22193. Epub 2020 Nov 22.

The C-terminal fragment of the heavy chain of the tetanus toxin (Hc-TeTx) improves motor activity and neuronal morphology in the limbic system of aged mice.

Synapse (New York, N.Y.)

Ruben Vazquez-Roque, Mariana Pacheco-Flores, Julio Cesar Penagos-Corzo, Gonzalo Flores, José Aguilera, Samuel Treviño, Jorge Guevara, Alfonso Diaz, Berenice Venegas

PMID: 33141999 DOI: 10.1002/syn.22193

Abstract

In the aging process, the brain presents biochemical and morphological alterations. The neurons of the limbic system show reduced size dendrites, in addition to the loss of dendritic spines. These disturbances trigger a decrease in motor and cognitive function. Likewise, it is reported that during aging, in the brain, there is a significant decrease in neurotrophic factors, which are essential in promoting the survival and plasticity of neurons. The carboxyl-terminal fragment of the heavy chain of the tetanus toxin (Hc-TeTx) acts similarly to neurotrophic factors, inducing neuroprotection in different models of neuronal damage. The aim here, was to evaluate the effect of Hc-TeTx on the motor processes of elderly mice (18 months old), and its impact on the dendritic morphology and density of dendritic spines of neurons in the limbic system. The morphological analysis in the dendrites was evaluated employing Golgi-Cox staining. Hc-TeTx was administered (0.5 mg/kg) intraperitoneally for three days in 18-month-old mice. Locomotor activity was evaluated in a novel environment 30 days after the last administration of Hc-TeTx. Mice treated with Hc-TeTx showed significant changes in their motor behavior, and an increased dendritic spine density of pyramidal neurons in layers 3 and 5 of the prefrontal cortex in the hippocampus, and medium spiny neurons of the nucleus accumbens (NAcc). In conclusion, the Hc-TeTx improves the plasticity of the brain regions of the limbic system of aged mice. Therefore, it is proposed as a pharmacological alternative to prevent or delay brain damage during aging.

© 2020 Wiley Periodicals, Inc.

Keywords: carboxil-terminal fragment of heavy chain of tetanus toxin; dendritic spines; golgi-cox staining; locomotor activity; nucleus accumbens

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