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Biosynthesis and biological action of pineal allopregnanolone.

Tsutsui K, Haraguchi S - Front Cell Neurosci (2014)

Bottom Line: Subsequently, we have demonstrated the biological action of pineal allopregnanolone on Purkinje cells in the cerebellum during development in juvenile birds.Pinealectomy (Px) induces apoptosis of Purkinje cells, whereas allopregnanolone administration to Px chicks prevents cell death.Furthermore, Px increases the number of Purkinje cells that express active caspase-3, a crucial mediator of apoptosis, and allopregnanolone administration to Px chicks decreases the number of Purkinje cells expressing active caspase-3.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Integrative Brain Sciences, Department of Biology and Center for Medical Life Science, Waseda University Tokyo, Japan.

ABSTRACT
The pineal gland transduces photoperiodic changes to the neuroendocrine system by rhythmic secretion of melatonin. We recently provided new evidence that the pineal gland is a major neurosteroidogenic organ and actively produces a variety of neurosteroids de novo from cholesterol in birds. Notably, allopregnanolone is a major pineal neurosteroid that is far more actively produced in the pineal gland than the brain and secreted by the pineal gland in juvenile birds. Subsequently, we have demonstrated the biological action of pineal allopregnanolone on Purkinje cells in the cerebellum during development in juvenile birds. Pinealectomy (Px) induces apoptosis of Purkinje cells, whereas allopregnanolone administration to Px chicks prevents cell death. Furthermore, Px increases the number of Purkinje cells that express active caspase-3, a crucial mediator of apoptosis, and allopregnanolone administration to Px chicks decreases the number of Purkinje cells expressing active caspase-3. It thus appears that pineal allopregnanolone prevents cell death of Purkinje cells by suppressing the activity of caspase-3 during development. This paper highlights new aspects of the biosynthesis and biological action of pineal allopregnanolone.

No MeSH data available.


Neuroprotective action of pineal allopregnanolone on Purkinje cell survival during cerebellar development. The square in the left bottom indicates the location of the pineal gland in the quail chick brain. The pineal gland is located adjacent to the cerebellum. Allopregnanolone is exceedingly produced in the pineal gland compared with brain regions, and may affect the adjacent cerebellar Purkinje cells by diffusion, and saves Purkinje cells from apoptosis in the juvenile quail. Secreted pineal allopregnanolone inhibits the expression of active caspase-3 that facilitates apoptosis of Purkinje cells in the cerebellum during development. See Haraguchi et al. (2012b) and the text for details.
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Figure 2: Neuroprotective action of pineal allopregnanolone on Purkinje cell survival during cerebellar development. The square in the left bottom indicates the location of the pineal gland in the quail chick brain. The pineal gland is located adjacent to the cerebellum. Allopregnanolone is exceedingly produced in the pineal gland compared with brain regions, and may affect the adjacent cerebellar Purkinje cells by diffusion, and saves Purkinje cells from apoptosis in the juvenile quail. Secreted pineal allopregnanolone inhibits the expression of active caspase-3 that facilitates apoptosis of Purkinje cells in the cerebellum during development. See Haraguchi et al. (2012b) and the text for details.

Mentions: The two major pineal neurosteroids, 7α-hydroxypregnenolone and allopregnanolone, are abundantly released from the pineal gland during development (Haraguchi et al., 2012b). Therefore, these major pineal neurosteroids may play important roles in the avian brain during development. In birds, the pineal gland is located near the cerebellum (Figure 2). The Purkinje cell integrates the process of memory and learning. It has been reported that, in birds and mammals, pinealectomy (Px) induces cell loss in the brain including Purkinje cells during development (Kilic et al., 2002; Tunç et al., 2006). Based on these findings, we hypothesized that allopregnanolone and/or 7α-hydroxypregnenolone secreted by the pineal gland may play a role in preventing the death of developing Purkinje cells. To test this hypothesis, we conducted a series of experiments in the male juvenile birds. Px decreased the concentration of allopregnanolone in the cerebellum and induced apoptosis of Purkinje cells, whereas administration of allopregnanolone to Px birds increased allopregnanolone concentration in the cerebellum and prevented apoptosis of Purkinje cells (Haraguchi et al., 2012b). We further indicated that pineal allopregnanolone reaches Purkinje cells in the cerebellum by diffusion shown by injection of 3H-allopregnanolone close to the pineal lumen (Haraguchi et al., 2012b). Thus, allopregnanolone secreted by the pineal gland is considered to be a key factor for Purkinje cell survival during development (Figure 2).


Biosynthesis and biological action of pineal allopregnanolone.

Tsutsui K, Haraguchi S - Front Cell Neurosci (2014)

Neuroprotective action of pineal allopregnanolone on Purkinje cell survival during cerebellar development. The square in the left bottom indicates the location of the pineal gland in the quail chick brain. The pineal gland is located adjacent to the cerebellum. Allopregnanolone is exceedingly produced in the pineal gland compared with brain regions, and may affect the adjacent cerebellar Purkinje cells by diffusion, and saves Purkinje cells from apoptosis in the juvenile quail. Secreted pineal allopregnanolone inhibits the expression of active caspase-3 that facilitates apoptosis of Purkinje cells in the cerebellum during development. See Haraguchi et al. (2012b) and the text for details.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4017145&req=5

Figure 2: Neuroprotective action of pineal allopregnanolone on Purkinje cell survival during cerebellar development. The square in the left bottom indicates the location of the pineal gland in the quail chick brain. The pineal gland is located adjacent to the cerebellum. Allopregnanolone is exceedingly produced in the pineal gland compared with brain regions, and may affect the adjacent cerebellar Purkinje cells by diffusion, and saves Purkinje cells from apoptosis in the juvenile quail. Secreted pineal allopregnanolone inhibits the expression of active caspase-3 that facilitates apoptosis of Purkinje cells in the cerebellum during development. See Haraguchi et al. (2012b) and the text for details.
Mentions: The two major pineal neurosteroids, 7α-hydroxypregnenolone and allopregnanolone, are abundantly released from the pineal gland during development (Haraguchi et al., 2012b). Therefore, these major pineal neurosteroids may play important roles in the avian brain during development. In birds, the pineal gland is located near the cerebellum (Figure 2). The Purkinje cell integrates the process of memory and learning. It has been reported that, in birds and mammals, pinealectomy (Px) induces cell loss in the brain including Purkinje cells during development (Kilic et al., 2002; Tunç et al., 2006). Based on these findings, we hypothesized that allopregnanolone and/or 7α-hydroxypregnenolone secreted by the pineal gland may play a role in preventing the death of developing Purkinje cells. To test this hypothesis, we conducted a series of experiments in the male juvenile birds. Px decreased the concentration of allopregnanolone in the cerebellum and induced apoptosis of Purkinje cells, whereas administration of allopregnanolone to Px birds increased allopregnanolone concentration in the cerebellum and prevented apoptosis of Purkinje cells (Haraguchi et al., 2012b). We further indicated that pineal allopregnanolone reaches Purkinje cells in the cerebellum by diffusion shown by injection of 3H-allopregnanolone close to the pineal lumen (Haraguchi et al., 2012b). Thus, allopregnanolone secreted by the pineal gland is considered to be a key factor for Purkinje cell survival during development (Figure 2).

Bottom Line: Subsequently, we have demonstrated the biological action of pineal allopregnanolone on Purkinje cells in the cerebellum during development in juvenile birds.Pinealectomy (Px) induces apoptosis of Purkinje cells, whereas allopregnanolone administration to Px chicks prevents cell death.Furthermore, Px increases the number of Purkinje cells that express active caspase-3, a crucial mediator of apoptosis, and allopregnanolone administration to Px chicks decreases the number of Purkinje cells expressing active caspase-3.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Integrative Brain Sciences, Department of Biology and Center for Medical Life Science, Waseda University Tokyo, Japan.

ABSTRACT
The pineal gland transduces photoperiodic changes to the neuroendocrine system by rhythmic secretion of melatonin. We recently provided new evidence that the pineal gland is a major neurosteroidogenic organ and actively produces a variety of neurosteroids de novo from cholesterol in birds. Notably, allopregnanolone is a major pineal neurosteroid that is far more actively produced in the pineal gland than the brain and secreted by the pineal gland in juvenile birds. Subsequently, we have demonstrated the biological action of pineal allopregnanolone on Purkinje cells in the cerebellum during development in juvenile birds. Pinealectomy (Px) induces apoptosis of Purkinje cells, whereas allopregnanolone administration to Px chicks prevents cell death. Furthermore, Px increases the number of Purkinje cells that express active caspase-3, a crucial mediator of apoptosis, and allopregnanolone administration to Px chicks decreases the number of Purkinje cells expressing active caspase-3. It thus appears that pineal allopregnanolone prevents cell death of Purkinje cells by suppressing the activity of caspase-3 during development. This paper highlights new aspects of the biosynthesis and biological action of pineal allopregnanolone.

No MeSH data available.