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Neurodevelopmental Disorders

開催日 2014/9/12
時間 11:00 - 12:00
会場 Poster / Exhibition(Event Hall B)

Cerebral developmental trace in a rat model of cryptogenic infantile spasms

  • P2-365
  • 辻 恵 / Megumi Tsuji:1 高橋 由香里 / Yukari Takahashi:1 渡部 文子 / Ayako M Watabe:1 加藤 総夫 / Fusao Kato:1 
  • 1:東京慈恵会医科大学大学院 / Department of Neuroscience, Jikei University School of Medicine 

Cognitive and psychological deficits in the adulthood are frequently reported symptoms in the patients who experienced epileptic episodes in infancy and childhood. In particular, 70-80% of mature patients with a history of cryptogenic infantile spasms (IS) early in life present mental retardation and cognitive deficits, suggesting that IS in the very early period of life affects development and maturation of the neuronal network integrity underlying cognito-psychological functions. However, cellular and synaptic analyses of the forebrain function in developed adult animal models have been difficult primarily due to the heterogenous IS etiology and also due to the difficulties in making adult ex-vivo preparations suitable for long-term recordings. We overcame these limitations by using the recently developed animal model of cryptogenic IS (Velisek et al., 2010) and also the advanced techniques for creating viable ex vivo preparations. Pregnant SD rats were treated with betamethasone and the offsprings received 3 injections of NMDA on postnatal days 12-15 (NMDA group) or saline (saline group). A subset of animals was treated with ACTH in parallel with NMDA injections (ACTH group). The rats of NMDA group consistently showed acute flexion spasms with EEG abnormalities. After weaning, the rats were raised until postnatal week 6-10 at which the hippocampal slices were made to analyze long-term potentiation (LTP) in the CA1 region. Whereas the high-frequency stimulation of the Schaffer collateral at 100 Hz resulted in significant LTP to degrees not significantly different between three groups, theta burst stimulation gave rise to significantly more potent LTP in the male NMDA group than in the saline group (n=13, 16; P<0.05), in the slices showing robust and stable long-term potentiation for 45 min. Such exaggerated hippocampal LTP was not accompanied by apparent macroscopic aberrancy in the hippocampus in any group. These results suggest that the functional synaptic integrity of the forebrain networks in the mature hippocampus remains affected even at 6-10 weeks after the occurrence of IS-like aberrant activity in the early stage of life, presumably providing basis for cognitive impairments.

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