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.

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.

Natural products present neurotrophic properties in neurons of the limbic system in aging rodents.

Aging is a complex process that can lead to neurodegeneration and, consequently, several pathologies, including dementia. Physiological aging leads to changes in several body organs, including those of the central nervous system (CNS). Morphological changes in the CNS and particularly the brain result in motor and cognitive deficits affecting learning and memory and the circadian cycle. Characterizing neural modifications is critical to designing new therapies to target aging and associated pathologies. In this review, we compared aging to the changes occurring within the brain and particularly the limbic system. Then, we focused on key natural compounds, apamin, cerebrolysin, Curcuma longa, resveratrol, and N-PEP-12, which have shown neurotrophic effects particularly in the limbic system. Finally, we drew our conclusions delineating future perspectives for the development of novel natural therapeutics to ameliorate aging-related processes.