Localization of 5-HT1A receptors to astroglial cells in adult rats: implications for neuronal-glial interactions and psychoactive drug mechanism of action

P. M. Whitaker-Azmitia, C. Clarke, E. C. Azmitia

Research output: Contribution to journalArticle

Abstract

Although tissue culture studies have shown a variety of neurotransmitter receptors on astroglial cells, verifying these observations in adult animals has been difficult and rarely accomplished. In the current study we have used double immunocytochemistry to localize 5-HT1a receptors to astroglial cells in fixed sections of adult rat brain. The astroglial cells were identified using an antibody raised against the astroglial-specific protein glial fibrillary acidic protein (GFAP). To label the 5-HT1a receptor, we used an antibody we recently raised against a unique peptide sequence occurring in the second extracellular loop of the receptor. Our results show that the 5-HT1a receptor occurs in relatively high abundance on astroglial cells. There is regional specificity, the receptor being much more commonly found in septum and hippocampus than striatum. There are also intraregional differences in that even within a single brain region one astrocyte may have very high levels of the receptor while an adjacent cell has none. We propose that the cellular localization of this receptor could have significance in understanding the mechanism of action of 5-HT1a receptor active drugs in alleviating anxiety and depression. The mechanism may be through the release of a neurotrophic agent, S-100 beta, from astrocytes. This factor may then cause regeneration or sprouting of neuronal terminals which have been lost due to a disease process.
Original languageUndefined
Pages (from-to)201-5
JournalSynapse
Volume14
Issue number3
DOIs
StatePublished - 1993

Keywords

  • Animals Antidepressive Agents/pharmacology Astrocytes/cytology/drug effects/metabolism/*physiology Brain/cytology/metabolism/*physiology Cell Communication Glial Fibrillary Acidic Protein/analysis Hippocampus/cytology/metabolism/*physiology Immunohistochemistry Nerve Growth Factors Neuroglia/cytology/drug effects/*physiology Neurons/cytology/drug effects/*physiology Rats Rats, Sprague-Dawley Receptors, Serotonin/analysis/*metabolism S100 Calcium Binding Protein beta Subunit S100 Proteins/metabolism

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Localization of 5-HT1A receptors to astroglial cells in adult rats: implications for neuronal-glial interactions and psychoactive drug mechanism of action. / Whitaker-Azmitia, P. M.; Clarke, C.; Azmitia, E. C.

In: Synapse, Vol. 14, No. 3, 1993, p. 201-5.

Research output: Contribution to journalArticle

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abstract = "Although tissue culture studies have shown a variety of neurotransmitter receptors on astroglial cells, verifying these observations in adult animals has been difficult and rarely accomplished. In the current study we have used double immunocytochemistry to localize 5-HT1a receptors to astroglial cells in fixed sections of adult rat brain. The astroglial cells were identified using an antibody raised against the astroglial-specific protein glial fibrillary acidic protein (GFAP). To label the 5-HT1a receptor, we used an antibody we recently raised against a unique peptide sequence occurring in the second extracellular loop of the receptor. Our results show that the 5-HT1a receptor occurs in relatively high abundance on astroglial cells. There is regional specificity, the receptor being much more commonly found in septum and hippocampus than striatum. There are also intraregional differences in that even within a single brain region one astrocyte may have very high levels of the receptor while an adjacent cell has none. We propose that the cellular localization of this receptor could have significance in understanding the mechanism of action of 5-HT1a receptor active drugs in alleviating anxiety and depression. The mechanism may be through the release of a neurotrophic agent, S-100 beta, from astrocytes. This factor may then cause regeneration or sprouting of neuronal terminals which have been lost due to a disease process.",
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N2 - Although tissue culture studies have shown a variety of neurotransmitter receptors on astroglial cells, verifying these observations in adult animals has been difficult and rarely accomplished. In the current study we have used double immunocytochemistry to localize 5-HT1a receptors to astroglial cells in fixed sections of adult rat brain. The astroglial cells were identified using an antibody raised against the astroglial-specific protein glial fibrillary acidic protein (GFAP). To label the 5-HT1a receptor, we used an antibody we recently raised against a unique peptide sequence occurring in the second extracellular loop of the receptor. Our results show that the 5-HT1a receptor occurs in relatively high abundance on astroglial cells. There is regional specificity, the receptor being much more commonly found in septum and hippocampus than striatum. There are also intraregional differences in that even within a single brain region one astrocyte may have very high levels of the receptor while an adjacent cell has none. We propose that the cellular localization of this receptor could have significance in understanding the mechanism of action of 5-HT1a receptor active drugs in alleviating anxiety and depression. The mechanism may be through the release of a neurotrophic agent, S-100 beta, from astrocytes. This factor may then cause regeneration or sprouting of neuronal terminals which have been lost due to a disease process.

AB - Although tissue culture studies have shown a variety of neurotransmitter receptors on astroglial cells, verifying these observations in adult animals has been difficult and rarely accomplished. In the current study we have used double immunocytochemistry to localize 5-HT1a receptors to astroglial cells in fixed sections of adult rat brain. The astroglial cells were identified using an antibody raised against the astroglial-specific protein glial fibrillary acidic protein (GFAP). To label the 5-HT1a receptor, we used an antibody we recently raised against a unique peptide sequence occurring in the second extracellular loop of the receptor. Our results show that the 5-HT1a receptor occurs in relatively high abundance on astroglial cells. There is regional specificity, the receptor being much more commonly found in septum and hippocampus than striatum. There are also intraregional differences in that even within a single brain region one astrocyte may have very high levels of the receptor while an adjacent cell has none. We propose that the cellular localization of this receptor could have significance in understanding the mechanism of action of 5-HT1a receptor active drugs in alleviating anxiety and depression. The mechanism may be through the release of a neurotrophic agent, S-100 beta, from astrocytes. This factor may then cause regeneration or sprouting of neuronal terminals which have been lost due to a disease process.

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