ASDモデルにおける触覚関連フェノタイプを改善するために,外周的体感神経をターゲットにする
Lauren L Orefice1, Jacqueline R Mosko1, Danielle T Morency1
1Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA; Howard Hughes Medical Institute, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA.
Cell
|August 10, 2019
まとめ
自閉症スペクトル障害 (ASD) の感覚過剰反応の治療は困難です. この研究では,GABA A受容体アゴニストによる外周機械感覚神経を標的としたことが,マウスモデルにおける触覚過敏症およびASDに関連するいくつかの行動を効果的に減少させたことが判明しました.
科学分野:
- 神経科学
- 発達生物学
- 遺伝学
背景:
- 自閉症スペクトル障害 (ASD) の一般的な特徴は,潜在的にコア行動症状に寄与する.
- 感覚的過剰反応とASDの現在の治療法は限られており,新しい治療方法の必要性を強調しています.
研究 の 目的:
- 異なる自閉症スペクトル障害 (ASD) のマウスモデルにおける体感覚過剰反応の病理生理学的メカニズムを調査する.
- ASDに関連する感覚異常や行動に対する治療戦略として,外周的メカニカセンサリーニューロンを標的とする可能性を探る.
主な方法:
- Shank3 と Mecp2 の変異性ASDマウスモデルで異なる体感覚神経の病理学的メカニズムを調べた.
- 周回局限性GABAA受容体アゴニストによる急性および慢性治療の作用を研究した.
- タクティルの過剰反応,不安のような行動,社会的障害,記憶,運動の欠陥,過剰な整形など,評価された行動の結果.
主要な成果:
- 周辺の機械感覚神経細胞における発達性遺伝子喪失 (Shank3,Mecp2) は,地域特有の脳異常を引き起こし,ASDに関連する行動に寄与した.
- GABAA受容体アゴニストによる急性治療は,6つの異なるASDマウスモデルで感触性過剰反応を著しく減少させた.
- 慢性的な治療は Mecp2とShank3変異マウスの特定の身体的および行動的側面を改善したが,すべての欠陥が改善されたわけではない.
結論:
- 外周機械感覚神経機能障害は,ASDマウスモデルにおける触覚異常および関連する行動に役割を果たします.
- GABAA受容体アゴニストによる外周機械感覚神経を標的とした治療は,ASDにおける触覚性過剰反応に対する有望な治療方法である.
- このアプローチはASDに関連する特定の行動に対処するための戦略を提供できるが,より広範な応用にはさらなる研究が必要である.
関連する概念動画
01:27Tactile and Chemical Senses
727
Tactile senses encompass touch, temperature, and pain, each mediated by specific receptors. Touch receptors detect mechanical energy or pressure against the skin. Sensory fibers from these receptors enter the spinal cord and relay information to the brain stem. Here, most fibers cross over to the opposite side of the brain. The touch information then moves to the thalamus, which projects a map of the body's surface onto the somatosensory areas of the parietal lobes in the cerebral cortex.
727
01:11Sensory Perception: Organization of the Somatosensory System
11.1K
The somatosensory system is the central and peripheral nervous system component that senses and processes touch, pressure, pain, temperature, and body position or proprioception. The process of sensation takes place at three levels:
The receptor level:
The receptor level is the first stage of sensation. It involves the detection of a stimulus by specialized sensory receptors. The stimulus must arrive within the receptor's receptive field. Next, the receptor converts the energy of the...
The receptor level:
The receptor level is the first stage of sensation. It involves the detection of a stimulus by specialized sensory receptors. The stimulus must arrive within the receptor's receptive field. Next, the receptor converts the energy of the...
11.1K
01:23Somatosensory, Motor, and Association Cortex
2.4K
The somatosensory cortex in the parietal lobes is crucial for interpreting sensory data such as touch, temperature, and proprioception. The somatosensory cortex, situated in the parietal lobes, plays a vital role in interpreting sensory information like touch, temperature, and proprioception—awareness of body position. This specialized brain region features an organized structure wherein neurons at the top primarily process sensations originating from the lower body. In contrast, those at...
2.4K
02:07Improving Translational Accuracy
14.1K
Base complementarity between the three base pairs of mRNA codon and the tRNA anticodon is not a failsafe mechanism. Inaccuracies can range from a single mismatch to no correct base pairing at all. The free energy difference between the correct and nearly correct base pairs can be as small as 3 kcal/ mol. With complementarity being the only proofreading step, the estimated error frequency would be one wrong amino acid in every 100 amino acids incorporated. However, error frequencies observed in...
14.1K
02:07Improving Translational Accuracy
3.6K
3.6K
02:27Background and Environment Affect Phenotype
7.4K
Although the genetic makeup of an organism plays a major role in determining the phenotype, there are also several environmental factors, such as temperature, oxygen availability, presence of mutagens, that can alter an organism’s phenotype.
An example of how genetic background affects phenotype can be seen in horses. The Extension gene in horses is responsible for their coat color. A wild-type gene (EE) produces black pigment in the coat, while a mutant gene (ee) produces red pigment. A...
An example of how genetic background affects phenotype can be seen in horses. The Extension gene in horses is responsible for their coat color. A wild-type gene (EE) produces black pigment in the coat, while a mutant gene (ee) produces red pigment. A...
7.4K