Maternal Creatine Supplementation Positively Affects Male Rat Hippocampal Synaptic Plasticity in Adult Offspring

Abstract

Creatine plays a crucial role in developing the brain, so much that its genetic deficiency results in mental dysfunction and cognitive impairments. Moreover, creatine supplementation is currently under investigation as a preventive measure to protect the fetus against oxidative stress during difficult pregnancies. Although creatine use is considered safe, posing minimal risk to clinical health, we found an alteration in morpho-functional maturation of neurons when male rats were exposed to creatine loads during brain development. In particular, increased excitability and enhanced long-term potentiation (LTP) were observed in the hippocampal pyramidal neurons of weaning pups. Since these effects were observed a long time after creatine treatment had been terminated, long-lasting modifications persisting into adulthood were hypothesized. Such modifications were investigated in the present study using morphological, electrophysiological, and calcium imaging techniques applied to hippocampal Cornu Ammonis 1 (CA1) neurons of adult rats born from dams supplemented with creatine. When compared to age-matched controls, the treated adult offspring were found to retain enhanced neuron excitability and an improved LTP, the best-documented neuronal substrate for memory formation. While translating data from rats to humans does have limitations, our findings suggest that prenatal creatine supplementation could have positive effects on adult cognitive abilities.

Calsequestrin Deletion Facilitates Hippocampal Synaptic Plasticity and Spatial Learning in Post-Natal Development

“…Ca 2+ imaging recordings were carried as previously described [ 93 , 94 ]. Briefly, the experiments were carried out using a Zeiss Axioskop microscope (Carl Zeiss International, Milan, Italy) equipped with a 40× water immersion objective and the Orca Flash 4.0 CCD camera (C11440, Hamamatsu, Japan), an Axopatch-200B amplifier (Axon Instruments, San Jose, CA, USA), and WinFluor software (Strathclyde Imaging Software V 3.8.7, John Dempster, University of Strathclyde, UK).…”

“…In each recorded neuron, the endogenous buffer capacity (κ S ), unperturbed Ca 2+ transient, and intracellular Ca 2+ concentration at resting condition [Ca 2+ ] 0 and during a single action potential Δ[Ca 2+ ] AP were calculated according to Maravall and collegues [ 95 ], as previously described [ 93 ].…”

Nutraceuticals in the Prevention of Neonatal Hypoxia–Ischemia: A Comprehensive Review of their Neuroprotective Properties, Mechanisms of Action and Future Directions

“…For instance, creatine supplementation during pregnancy was shown to positively affect the morphological and electrophysiological development of hippocampal neurons in offspring rats, increasing neuronal excitability [ 268 ]. These positive effects were maintained in adult rats, which retained enhanced neuron excitability and long-term potentiation [ 269 ]. Creatine administered during pregnancy was shown to cross the placenta and reach several organs of the fetus, and, in fact, maternal creatine supplementation has been proposed as prophylaxis to protect the fetus from the multiorgan consequences of severe hypoxia at birth [ 270 ].…”

GABAergic Input Affects Intracellular Calcium Levels in Developing Granule Cells of Adult Rat Hippocampus

“…Calcium imaging recordings were performed in whole-cell configuration using Fluo-4 pentapotassium salt, a calcium indicator dye (Thermo Fisher, Waltham, MA, USA), as previously described [34]. Briefly, the experiments were carried out using a Zeiss Axioskop microscope (Carl Zeiss International, Italy) equipped with a 40× water immersion objective and the Orca Flash 4.0 CCD camera (C11440, Hamamatsu, Japan), an Axopatch-200B amplifier (Axon Instruments, San Jose, CA, USA) and WinFluor software (Strathclyde Imaging Software V 3.8.7, John Dempster, University of Strathclyde, UK).…”