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communication challenges, as well as abnormal repetitive and restrictive behaviors. It is reported that ASD occur in all racial, ethnic and socioeconomic groups, yet are about four times more likely to occur in boys than in girls probably due to the extremes of typical male

The relationship between immune disorders and ASD has been proposed based on series of evidences.Secondly, genetic predisposition is considered to be involved in the etiology of ASD. Cumulative evidences indicated ASD had a strong genetic background, both genegene and gene-environment interactions attribute to the etiology of autism. Also, it's now generally accepted that ASD is a group of multi-genetic diseases, in which environmental factors play an important part. Given the early onset of the symptoms, prenatal exposures to environmental challenges are considered the major risk factors leading to subsequent mortality of ASD. Various factors have been proven to be potentially detrimental to early neurosystem development, including maternal use of pharmaceutical agents with neurotoxic effects, intrauterine exposure to viral infections or maternal stress , as well as exposure to high levels of environmental pollutants such as heavy metals . Similarly, neonatal exposure to such risk factors may also lead to mortality of ASD, which has been

At last, ASD animal models provide a feasible and relatively easy way to morphologically and functionally study the etiology of ASD in different levels, and to testify the effectiveness of the potential interventions. Recent advances in this field provide both inbred strains such as BTBR *T+ tf/J* mice and mutant lines. Other mice models for fragile X syndrome, Rett syndrome have also been used for autism related studies due to the autistic-like behaviors

In conclusion, data remain inconclusive for the majority of candidate genes tested so far. Still, we have good reason to be optimistic regarding gene discovery in ASD now and in the future. Cytogenetic, linkage, association studies and array analysis have provided promising results. Emerging genetic technologies and analysis tools offer even more powerful approaches for developing insights into the etiology of ASD. In addition, genetic studies facilitate other autism research such as biochemical and neuroimaging studies, which will, in turn, provide evidence and valuable clues to direct future genetic studies.

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**27** 

Hideto To

*Japan* 

*University of Toyama* 

**Chronobiology of and Chronotherapy** 

Most humans have a relatively regular activity pattern (sleep, labor, and meal etc.). This activity can be roughly classified into the rest phase and active phase, and body temperature, heart rate, blood pressure, and the dominance of the sympathetic and parasympathetic nerves differ in each phase. These variations display daily rhythms, which

For instance, ICR mice, which were housed under standardized light-dark cycle conditions (lights-on and lights-off at 7:00 and 19:00, respectively) at a room temperature of 24 ± 1oC (range) and a relative humidity of 60 ± 10% (range) and were allowed free access to food and water displayed a circadian rhythm in their leukocyte counts with a peak at noon and a trough at midnight (Fig. 1). Many organisms display rhythms in various factors (Table 1). In humans, heart rate and blood pressure decline at night. We spend much of our time in a standing position during the day and sleep in a recumbent position at night. It is thought that the wake-sleep transition and endogenous circadian rhythms are responsible for the circadian rhythms in heart rate and blood pressure. Circadian rhythms also exist for the

**1. Introduction** 

are known as circadian rhythms.

Fig. 1. Circadian rhythm of mouse leukocyte count

**for Rheumatoid Arthritis** 

