Insulin Normalizes Ionic Homeostasis and the State of Mitochondria after a Mechanical Damage to the Culture of Brain Neurons

• Published in: Biochemistry (Moscow). Supplement series A, Membrane and cell biology Vol. 15; no. 4; pp. 365 - 371
• Main Authors: Krasilnikova, I. A., Pomytkin, I. A., Pinelis, V. G., Surin, A. M.
• Format: Journal Article
• Language: English
• Published: Moscow Pleiades Publishing 01-10-2021; Springer Nature B.V
• Subjects: Biomedical and Life Sciences; Brain damage; Calcium (intracellular); Calcium homeostasis; Calcium ions; Cell Biology; Cell culture; Deregulation; Homeostasis; Insulin; Life Sciences; Mitochondria; Neural networks; Neurons; Traumatic brain injury; glutamate excitotoxicity; insulin; mechanical brain damage in vitro; delayed calcium deregulation
• ISSN: 1990-7478; 1990-7494
• DOI: 10.1134/S1990747821060064

Mechanical damage to the primary neuronal culture serves as a convenient in vitro model for studying the molecular and cellular mechanisms involved in the spread of the lesion in mechanical brain trauma. In this study, changes in the intracellular concentrations of Ca
2+
([Ca
2+
]
i
) and Na
+
([Na
+
]
i
), as well as mitochondrial potential (ΔΨ
m
) in response to mechanical damage to the primary culture of rat cortical neurons were studied. Rapid (within 1–2 s) damage to the neuronal network in the form of an approximately 3 × 0.1-mm scratch caused an abrupt increase in [Ca
2+
]
i
and [Na
+
]
i
as well as a sharp drop in ΔΨ
m
. There was a gradual recovery of these parameters to the basal level in ~78% of the cells that responded to the culture damage. The second phase of the [Ca
2+
]
i
rise (delayed calcium deregulation, DCD), synchronous with a marked drop in ΔΨ
m
, occurred in 22% of the cells. In such cells, [Na
+
]
i
remained at the level of a high plateau. The addition of insulin (100 nM) 5 min before the mechanical damage reduced the proportion of neurons that had DCD and a sustained increase in [Na
+
]
i
. Thus, the presence of insulin contributed to the normalization of Ca
2+
and Na
+
homeostasis and the functioning of mitochondria, which were impaired under the in vitro simulation of mechanical brain trauma.