Author response: Light-at-night exposure affects brain development through pineal allopregnanolone-dependent mechanisms

Haraguchi, Shogo; Kamata, Masaki; Tokita, Takuma; K, Tashiro; Sato, Mitsuko; Nozaki, Mitsuki; Okamoto-Katsuyama, Mayumi; Shimizu, Isao; Han, Guofeng; Chowdhury, Vishwajit S.; Lei, Xiaofeng; Miyazaki, Takuro; Kim‐Kaneyama, Joo‐ri; Nakamachi, Tomoya; Matsuda, Kouhei; Ohtaki, Hirokazu; Tokumoto, Toshinobu; Tachibana, Tetsuya; Miyazaki, Akira; Tsutsui, Kazuyoshi

doi:10.7554/elife.45306.037

Cited by 1 publication

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“…It is known that neurosteroids are produced in glial cells and neurons of the central and peripheral nervous systems (1,5). However, we have demonstrated that the pineal gland produces neurosteroids from cholesterol in birds during early posthatch period (6)(7)(8). Notably, allopregnanolone (also known as 3α,5α-tetrahydroprogesterone; 3α,5α-THP) and 7αhydroxypregnenolone are the two major neurosteroids produced in the pineal gland (6,7).…”

Section: Introductionmentioning

confidence: 87%

“…Pinealectomy decreases the mRNA levels of pituitary adenylate cyclase-activating polypeptide (PACAP), a neuroprotective factor, in the cerebellum of juvenile birds (8). It has been found that a daily injection of allopregnanolone in pinealectomized juvenile birds upregulates PACAP relative to the levels in control birds (8). These findings show that PACAP mediates the neuroprotective action of pineal allopregnanolone through mPRα receptor binding during cerebellar development (Figure 2).…”

Section: Physiological Function Of Pineal Allopregnanolone In Purkinjmentioning

confidence: 96%

“…Therefore, either mPR siRNA or isoallopregnanolone, an antagonist of allopregnanolone, was delivered into the cerebellum of posthatched chicks. It was found that the silencing of mPRα increases the number of Purkinje cells that express active caspase-3 in the cerebellum of chicks (8). Furthermore, to uncover the mechanism of neuroprotective action of allopregnanolone in cerebellar Purkinje cells, allopregnanolone action on the expression of neuroprotective/neurotoxic factors (22)(23)(24)(25)(26) has been investigated.…”

Section: Physiological Function Of Pineal Allopregnanolone In Purkinjmentioning

confidence: 99%

“…Furthermore, to uncover the mechanism of neuroprotective action of allopregnanolone in cerebellar Purkinje cells, allopregnanolone action on the expression of neuroprotective/neurotoxic factors (22)(23)(24)(25)(26) has been investigated. Pinealectomy decreases the mRNA levels of pituitary adenylate cyclase-activating polypeptide (PACAP), a neuroprotective factor, in the cerebellum of juvenile birds (8). It has been found that a daily injection of allopregnanolone in pinealectomized juvenile birds upregulates PACAP relative to the levels in control birds (8).…”

Section: Physiological Function Of Pineal Allopregnanolone In Purkinjmentioning

confidence: 99%

“…Notably, allopregnanolone (also known as 3α,5α-tetrahydroprogesterone; 3α,5α-THP) and 7αhydroxypregnenolone are the two major neurosteroids produced in the pineal gland (6,7). Of these two, pineal allopregnanolone prevents the death of developing Purkinje cells (7,8), and pineal 7αhydroxypregnenolone functions as an up-regulator of locomotion, regulating locomotor activity in response to light stimuli in birds (6).…”

Section: Introductionmentioning

confidence: 99%

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Pineal Neurosteroids: Biosynthesis and Physiological Functions

Haraguchi

Tsutsui

2020

Front. Endocrinol.

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Similar to the adrenal glands, gonads, and placenta, vertebrate brains also produce various steroids, which are known as "neurosteroids." Neurosteroids are mainly synthesized in the hippocampus, hypothalamus, and cerebellum; however, it has recently been discovered that in birds, the pineal gland, a photosensitive region in the brain, produces more neurosteroids than other brain regions. A series of experiments using molecular and biochemical techniques have found that the pineal gland produces various neurosteroids, including sex steroids, de novo from cholesterol. For instance, allopregnanolone and 7α-hydroxypregnenolone are actively produced in the pineal gland, unlike in other brain regions. Pineal 7α-hydroxypregnenolone, an up-regulator of locomotion, enhances locomotor activity in response to light stimuli in birds. Additionally, pineal allopregnanolone acts on Purkinje cells in the cerebellum and prevents neuronal apoptosis within the developing cerebellum in juvenile birds. Furthermore, exposure to light during nighttime hours can cause loss of diurnal variations of pineal allopregnanolone synthesis during early posthatch life, eventually leading to cerebellar Purkinje cell death in juvenile birds. In light of these new findings, this review summarizes the biosynthesis and physiological functions of pineal neurosteroids. Given that the circadian rhythms of individuals in modern societies are constantly interrupted by artificial light exposure, these findings in birds, which are excellent model diurnal animals, may have direct implications for addressing problems regarding the mental health and brain development of humans.

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