TY - JOUR

T1 - Dynamic Foot Stimulations During Short-Term Hindlimb Unloading Prevent Dysregulation of the Neurotransmission in the Hippocampus of Rats

AU - Berezovskaya, Anna S.

AU - Tyganov, Sergey A.

AU - Nikolaeva, Svetlana D.

AU - Naumova, Alexandra A.

AU - Merkulyeva, Natalia S.

AU - Shenkman, Boris S.

AU - Glazova, Margarita V.

N1 - Berezovskaya, A.S., Tyganov, S.A., Nikolaeva, S.D. et al. Dynamic Foot Stimulations During Short-Term Hindlimb Unloading Prevent Dysregulation of the Neurotransmission in the Hippocampus of Rats. Cell Mol Neurobiol (2020). https://doi.org/10.1007/s10571-020-00922-2

PY - 2021/10

Y1 - 2021/10

N2 - Spaceflight and simulated microgravity both affect learning and memory, which are mostly controlled by the hippocampus. However, data about molecular alterations in the hippocampus in real or simulated microgravity conditions are limited. Adult Wistar rats were recruited in the experiments. Here we analyzed whether short-term simulated microgravity caused by 3-day hindlimb unloading (HU) will affect the glutamatergic and GABAergic systems of the hippocampus and how dynamic foot stimulation (DFS) to the plantar surface applied during HU can contribute in the regulation of hippocampus functioning. The results demonstrated a decreased expression of vesicular glutamate transporters 1 and 2 (VGLUT1/2) in the hippocampus after 3 days of HU, while glutamate decarboxylase 67 (GAD67) expression was not affected. HU also significantly induced Akt signaling and transcriptional factor CREB that are supposed to activate the neuroprotective mechanisms. On the other hand, DFS led to normalization of VGLUT1/2 expression and activity of Akt and CREB. Analysis of exocytosis proteins revealed the inhibition of SNAP-25, VAMP-2, and syntaxin 1 expression in DFS group proposing attenuation of excitatory neurotransmission. Thus, we revealed that short-term HU causes dysregulation of glutamatergic system of the hippocampus, but, at the same time, stimulates neuroprotective Akt-dependent mechanism. In addition, most importantly, we demonstrated positive effect of DFS on the hippocampus functioning that probably depends on the regulation of neurotransmitter exocytosis.

AB - Spaceflight and simulated microgravity both affect learning and memory, which are mostly controlled by the hippocampus. However, data about molecular alterations in the hippocampus in real or simulated microgravity conditions are limited. Adult Wistar rats were recruited in the experiments. Here we analyzed whether short-term simulated microgravity caused by 3-day hindlimb unloading (HU) will affect the glutamatergic and GABAergic systems of the hippocampus and how dynamic foot stimulation (DFS) to the plantar surface applied during HU can contribute in the regulation of hippocampus functioning. The results demonstrated a decreased expression of vesicular glutamate transporters 1 and 2 (VGLUT1/2) in the hippocampus after 3 days of HU, while glutamate decarboxylase 67 (GAD67) expression was not affected. HU also significantly induced Akt signaling and transcriptional factor CREB that are supposed to activate the neuroprotective mechanisms. On the other hand, DFS led to normalization of VGLUT1/2 expression and activity of Akt and CREB. Analysis of exocytosis proteins revealed the inhibition of SNAP-25, VAMP-2, and syntaxin 1 expression in DFS group proposing attenuation of excitatory neurotransmission. Thus, we revealed that short-term HU causes dysregulation of glutamatergic system of the hippocampus, but, at the same time, stimulates neuroprotective Akt-dependent mechanism. In addition, most importantly, we demonstrated positive effect of DFS on the hippocampus functioning that probably depends on the regulation of neurotransmitter exocytosis.

KW - Akt

KW - CREB

KW - Hippocampus

KW - Simulated microgravity

KW - SNARE proteins

KW - VGLUT1/2

KW - GLUTAMIC-ACID DECARBOXYLASE

KW - BDNF

KW - MICE LACKING

KW - 2

KW - SIMULATED MICROGRAVITY

KW - PROTEIN EXPRESSION

KW - VGLUT1

KW - GAMMA-AMINOBUTYRIC-ACID

KW - DENTATE GYRUS

KW - BRAIN

KW - SYNAPSIN-I

UR - http://www.scopus.com/inward/record.url?scp=85088114635&partnerID=8YFLogxK

UR - https://www.mendeley.com/catalogue/efe3092d-daa7-3d09-a3fd-dabe8ce3d426/

U2 - 10.1007/s10571-020-00922-2

DO - 10.1007/s10571-020-00922-2

M3 - Article

AN - SCOPUS:85088114635

VL - 41

SP - 1549

EP - 1561

JO - Cellular and Molecular Neurobiology

JF - Cellular and Molecular Neurobiology

SN - 0272-4340

IS - 7

ER -