Astrocytes in 17beta-estradiol treated mixed hippocampal cultures show attenuated calcium response to neuronal activity.
Glial cells in the brain are capable of responding to hormonal signals. The ovarian steroid hormone 17beta-estradiol, in addition to its actions on neurons, can directly affect glial cells. Estrogen receptors have been described on both neurons and astrocytes, suggesting a complex interplay between these two in mediating the effects of the hormone. Astrocytes sense and respond to neuronal activity with a rise in intracellular calcium concentration ([Ca(2+)](i)). Using simultaneous electrophysiology and calcium imaging techniques, we monitored neuronal activity evoked astrocyte ([Ca(2+)](i)) changes in mixed hippocampal cultures loaded with fluo-3 AM. Action potential firing in neurons, elicited by injecting depolarizing current pulses, was associated with ([Ca(2+)](i)) elevations in astrocytes, which could be blocked by 200 microM MCPG and also 1 microM TTX. We compared astrocytic ([Ca(2+)](i)) transients in control and 24-hour estradiol treated cultures. The amplitude of the ([Ca(2+)](i)) transient, the number of responsive astrocytes, and the ([Ca(2+)](i)) wave velocity were all significantly reduced in estradiol treated cultures. ([Ca(2+)](i)) rise in astrocytes in response to local application of the metabotropic glutamate receptor (mGluR) agonist t-ACPD was attenuated in estradiol treated cultures, suggesting functional changes in the astrocyte mGluR following 24-h treatment with estradiol. Since astrocytes can modulate synaptic transmission by release of glutamate, the attenuated ([Ca(2+)](i)) response seen following estradiol treatment could have functional consequences on astrocyte-neuron signaling.
Molecular Biophysics Unit, Indian Institute of Science, Bangalore, India.
Shilpa P
SP
Rao
S K
SK
Sikdar
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000814:Aniline Compounds; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D004558:Electric Stimulation; D004958:Estradiol / Q000494:pharmacology*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011960:Receptors, Estrogen / Q000819:agonists / Q000378:metabolism; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D026941:Sodium Channel Blockers / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology; D014966:Xanthenes
D000814:Aniline Compounds; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D011960:Receptors, Estrogen; D018094:Receptors, Metabotropic Glutamate; D026941:Sodium Channel Blockers; D014966:Xanthenes; C059715:Fluo-3; D004958:Estradiol; D002118:Calcium