Prenatal stress disturbs hippocampal KIF17 and NR2B in spatial cognition in male offspring

Abstract

Numerous studies have demonstrated that prenatal stress disturbs the hippocampal-mediated learning and memory processes in offspring. The underlying mechanisms for this effect, however, remain vague. It is well documented that N-methyl-D-aspartate (NMDA) receptors play a pivotal role in learning and memory, which are related to dynamically trafficking and regulating NMDA receptors by their response motor proteins. Over the past few years, increasing numbers of studies have elucidated that hippocampal-mediated learning and memory are regulated by KIF17 (kinesin superfamily motor protein 17), which specifically transports and regulates the NMDA receptor subunit NR2B in hippocampal neurons. The present study shows the influence of prenatal stress on KIF17 and NR2B expression and hippocampal NR2A/NR2B ratio partially reflecting function of KIF17, using mice as models. It was found that prenatal stress significantly decreased the hippocampal KIF17 and NR2B level in offspring at postnatal stages of 3 weeks and 9 weeks. Moreover, hippocampal KIF17 in the prenatally stressed pups continued to be weakened even after serial Morris water maze trainings, but not NR2B. Finally, the synaptic NR2A/NR2B level was upregulated in offspring exposed to prenatal stress, which revealed the dysfunction of KIF17. Thus, we conclude that prenatal stress leads to long-lasting deterioration of the expression and function of hippocampal KIF17 in offspring, which may be related to deficits of spatial cognition caused by prenatal stress. These data underpin the hypotheses that a physiopathology of neurodevelopmental origin in early life leads to defects in learning and memory in later life.

Environmental enrichment mitigates the sex-specific effects of gestational inflammation on social engagement and the hypothalamic pituitary adrenal axis-feedback system

“…For example, elevated hippocampal corticosterone combined with, or independent of, changes in glutamate and NR2B levels may be related to spatial disruptions in ACC-LPS males; although EE prevented most of these neurophysiological consequences of MIA, complex rearing did not protect against a reduction in hippocampal glutamate which may in part account for the sustained learning impairment in this group. Disruptions in the trafficking and assembly of NR2B (Kamphuis et al, 2003;Zhao et al, 2013), including synaptic NR2A/NR2B levels as mediated by kinesin superfamily motor protein 17 (Zhao et al, 2013), or changes in Ca 2+ /calmodulin-dependent protein kinase II (aCAM-KII) phosphorylation (Giese et al, 1998;Kamphuis et al, 2003) following MIA should also be considered. With respect to lower NR2B/actin ratios in the hippocampus of EE-saline rats, compared to ACC-saline controls, it seems that our EE housing environment modifies the glutamatergic system differently between these two groups.…”

“…Given that some early life stressors (i.e., gestational restraint, maternal separation) are associated with decreased hippocampal NMDA receptor NR2B subunits, and impaired synaptic plasticity and spatial processing (Son et al, 2006;Kamphuis et al, 2003;Roceri et al, 2002;Zhao et al, 2013), this receptor appeared to be a good candidate to account for the spatial memory deficits observed in our male ACC and EE animals following early gestational MIA. Therefore, we measured hippocampal levels of this receptor subunit by assessing NR2B/actin ratios, via densitometry and its associated transmitter, glutamate, utilizing LCMS-MS procedures.…”

Tualang honey improves memory and hippocampal changes in adult offspring of prenatally stressed rats

“…The reduced preference index indicating reduced recognition memory most probably is contributed by structural changes in the hippocampus. 21 Although the amount number of Nissl-positive neurons was not significantly different between stress and control group but there was altered characteristics of the neuronal cells. Prenatal stress has been shown to induce histological changes in the brain of rat offspring e.g.…”

“…The present study looked at the exploratory preference, a ratio of time spent exploring any one of the two objects (training) or the novel one (retention) over the total time spent exploring both objects. 21 The preference index (PI) used was an indicator of recognition memory and Hammond et al has suggested that PI above 50% indicates novel object preference, below 50% familiar object preference, and 50% no preference. 22…”

Estudio de biodisponibilidad de una mezcla de hidrocarburos en suelo modelo

“…Tal es el caso de la influencia del sistema serotoninérgico en el control de la actividad de las neuronas dopaminérgicas ya que es un factor fundamental en el humor y la emoción (113). Existe evidencia de que el estrés prenatal afecta la función cognitiva mediante la interrupción de la plasticidad sináptica en las sinapsis glutamatérgicas (114). El estrés prenatal disminuye el receptor NMDA en el hipocampo (115), el cual está relacionado con la potenciación a largo plazo y su disminución en esto favorece que la depresión a largo plazo aparezca.…”