Forebrain-specific ablation of phospholipase Cγ1 causes manic-like behavior

Yang, YR; Jung, Jung Hoon; Sj, Kim; Hamada, Kyohei; Suzuki, Akio; Kim, Hyung Jun; Jh, Lee; Ob, Kwon; Yk, Lee; Kim, J; Ek, Kim; Hj, Jang; Ds, Kang; Js, Choi; Cj, Lee; Marshall, John; Koh, HY; Kim, Chang‐Jin; Seok, Heon; Kim, SH; Choi, Jang Hyun; Choi, Yongbum; Cocco, Lucio; Ryu, Seung Wan; Kim, Jae‐Hun; Suh, Pann‐Ghill

doi:10.1038/mp.2016.261

Cited by 48 publications

(38 citation statements)

References 61 publications

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“…On the other hand, NO causes a neurotransmission inhibition through gamma-aminobutyric acid- (GABA-) ergic synaptic communication. It is associated with ion exchange and regulation of membrane excitation [ 21 , 22 ]. Moreover, NO as an important vasodilation factor mediates neurovascular coupling.…”

Section: Discussionmentioning

confidence: 99%

Benign Effect of Extremely Low‐Frequency Electromagnetic Field on Brain Plasticity Assessed by Nitric Oxide Metabolism during Poststroke Rehabilitation

Cichoń

Czarny

Bijak

et al. 2017

Oxidative Medicine and Cellular Longevity

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Nitric oxide (NO) is one of the most important signal molecules, involved in both physiological and pathological processes. As a neurotransmitter in the central nervous system, NO regulates cerebral blood flow, neurogenesis, and synaptic plasticity. The aim of our study was to investigate the effect of the extremely low-frequency electromagnetic field (ELF-EMF) on generation and metabolism of NO, as a neurotransmitter, in the rehabilitation of poststroke patients. Forty-eight patients were divided into two groups: ELF-EMF and non-ELF-EMF. Both groups underwent the same 4-week rehabilitation program. Additionally, the ELF-EMF group was exposed to an extremely low-frequency electromagnetic field of 40 Hz, 7 mT, for 15 min/day. Levels of 3-nitrotyrosine, nitrate/nitrite, and TNFα in plasma samples were measured, and NOS2 expression was determined in whole blood samples. Functional status was evaluated before and after a series of treatments, using the Activity Daily Living, Geriatric Depression Scale, and Mini-Mental State Examination. We observed that application of ELF-EMF significantly increased 3-nitrotyrosine and nitrate/nitrite levels, while expression of NOS2 was insignificantly decreased in both groups. The results also show that ELF-EMF treatments improved functional and mental status. We conclude that ELF-EMF therapy is capable of promoting recovery in poststroke patients.

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Section: Discussionmentioning

confidence: 99%

Benign Effect of Extremely Low‐Frequency Electromagnetic Field on Brain Plasticity Assessed by Nitric Oxide Metabolism during Poststroke Rehabilitation

Cichoń

Czarny

Bijak

et al. 2017

Oxidative Medicine and Cellular Longevity

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“…into the mice. Valproate or LiCl treatments were as previously reported 13,39 : valproate or LiCl were injected 3 times (10:00, 14:00 and 17:00) one day before the behavioral assays; and during the day of the behavioral assay, valproate or LiCl was injected 2 times (10:00, 14:00).…”

Section: Surgerymentioning

confidence: 99%

Dysfunction of ventral tegmental area GABA neurons causes mania-like behavior

Zhao

et al. 2019

Preprint

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The ventral tegmental area (VTA), an important source of dopamine, regulates goal-and reward-directed and social behaviors, wakefulness and sleep. Hyperactivation of dopamine neurons generates behavioral pathologies. But any roles of non-dopamine VTA neurons in psychiatric illness have been little explored. Lesioning or chemogenetically inhibiting VTA GABAergic (VTA Vgat ) neurons generated persistent wakefulness with mania-like qualities: locomotor activity was increased; sensitivity to D-amphetamine was heightened; immobility times decreased on the tail suspension and forced swim tests; and sucrose preference increased. Furthermore, after sleep deprivation, mice with lesioned VTA Vgat neurons did not catch up on the lost NREM sleep, even though they were starting from an already highly sleepdeprived baseline, suggesting that the sleep homeostasis process was bypassed. The manialike behaviors, including the sleep loss, were reversed by the mood-stabilizing drug valproate, and re-emerged when valproate treatment was stopped. Lithium salts, however, had no effect.The mania like-behaviors partially depended on dopamine, because giving D1/D2/D3 receptor antagonists partially restored the behaviors, but also on VTA Vgat projections to the lateral hypothalamus (LH). Optically or chemogenetically inhibiting VTA Vgat terminals in the LH elevated locomotion and decreased immobility time during the tail suspension and forced swimming tests. VTA Vgat neurons are centrally positioned to help set an animal's (and human's) level of mental and physical activity. Inputs that inhibit VTA Vgat neurons intensify wakefulness (increased activity, enhanced alertness and motivation), qualities useful for acute survival.Taken to the extreme, however, decreased or failed inhibition from VTA Vgat neurons produces mania-like qualities (hyperactivity, hedonia, decreased sleep).

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“…PLCγ1 cKO mice were generated by crossing K14‐cre transgenic mice (Jackson Laboratory) and PLCγ1 flox/flox mice . PLCγ1 cKO mice have been maintained on a mixed genetic background of 129SvJ and C57BL/6J.…”

Section: Methodsmentioning

confidence: 99%

Phospholipase Cγ1 is required for normal irritant contact dermatitis responses and sebaceous gland homeostasis

Nakamura

Kanemaru

Toyoda

et al. 2019

Experimental Dermatology

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Differentiation and proliferation of keratinocyte are controlled by various signalling pathways. The epidermal growth factor receptor (EGFR) is known to be an important regulator of multiple epidermal functions. Inhibition of EGFR signalling disturbs keratinocyte proliferation, differentiation and migration. Previous studies have revealed that one of the EGFR downstream signalling molecules, phospholipase Cγ1 (PLCγ1), regulates differentiation, proliferation and migration of keratinocytes in in vitro cell culture system. However, the role of PLCγ1 in the regulation of keratinocyte functions in animal epidermis remains unexplored. In this study, we generated keratinocyte‐specific PLCγ1 knockout (KO) mice (PLCγ1 cKO mice). Contrary to our expectations, loss of PLCγ1 did not affect differentiation, proliferation and migration of interfollicular keratinocytes. We further examined the role of PLCγ1 in irritant contact dermatitis (ICD), in which epidermal cells play a pivotal role. Upon irritant stimulation, PLCγ1 cKO mice showed exaggerated ICD responses. Further study revealed that epidermal loss of PLCγ1 induced sebaceous gland hyperplasia, indicating that PLCγ1 regulates homeostasis of one of the epidermal appendages. Taken together, our results indicate that, although PLCγ1 is dispensable in interfollicular keratinocyte for normal differentiation, proliferation and migration, it is required for normal ICD responses. Our results also indicate that PLCγ1 regulates homeostasis of sebaceous glands.

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Forebrain-specific ablation of phospholipase Cγ1 causes manic-like behavior

Cited by 48 publications

References 61 publications

Benign Effect of Extremely Low‐Frequency Electromagnetic Field on Brain Plasticity Assessed by Nitric Oxide Metabolism during Poststroke Rehabilitation

Benign Effect of Extremely Low‐Frequency Electromagnetic Field on Brain Plasticity Assessed by Nitric Oxide Metabolism during Poststroke Rehabilitation

Dysfunction of ventral tegmental area GABA neurons causes mania-like behavior

Phospholipase Cγ1 is required for normal irritant contact dermatitis responses and sebaceous gland homeostasis

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