Dynamic changes in AP-1 transcription factor DNA binding activity in rat brain following administration of antidepressant amitriptyline and brain-derived neurotrophic factor.

The present study was undertaken to examine the effects of the antidepressant, amitriptyline, and brain-derived neurotrophic factor (BDNF) on activator protein-1 (AP-1) DNA binding activity in the rat brain. Acute administration of amitriptyline (5 or 10 mg/kg) initially increased but then decreased AP-1 DNA binding activity in the rat frontal cortex and hippocampus. Chronic administration of amitriptyline (5 or 10 mg/kg, once daily for 3 weeks) initially decreased AP-1 DNA binding activity but ultimately resulted in its persistent elevation in the rat frontal cortex. In contrast, the chronic administration of amitriptyline did not affect the low activity of AP-1 DNA binding in the hippocampus. However, chronic administration of amitriptyline (10 mg/kg, once daily for 3 weeks) significantly increased BDNF protein levels in the hippocampus (by 26.9%) and frontal cortex (by 24.6%). Direct infusion of BDNF (1 microg) into the hippocampal dentate gyrus significantly increased hippocampal AP-1 DNA binding activity. These results suggest that AP-1 transcription factor may be modulated by BDNF and that it may be an important target for the action of antidepressants.

Genetic analysis in patients with familial and sporadic frontotemporal dementia: two tau mutations in only familial cases and no association with apolipoprotein epsilon4.

We screened for tau gene mutations among 24 Japanese (6 familial and 18 sporadic cases) and 4 Polish patients with frontotemporal dementia (FTD) using PCR-SSCP analysis followed by DNA sequencing. We identified 2 missense mutations in exon 10: N279K and P301L in 2 Japanese patients with familial FTD. Additionally 3 DNA polymorphisms: 2 known (3' exon 3 + 9, A --> G and exon 7, codon 176, G --> A) and 1 new (exon 8, codon 185, T --> C) were identified in 1 Polish patient. Tau mutations were not found in subjects with a negative family history suggesting that tau mutations do not account for most sporadic cases of FTD. We also found no association of apolipoprotein E4 allele with FTD.

Relationship between MRI findings and prognosis for patients with general paresis.

MRI was performed in 7 patients with general paresis before or at a very early stage of treatment. A large dose of antibiotics, mainly penicillin, was given to all patients, and the effects of treatment, the patients' outcome, and MRI findings were investigated. Three of the 7 patients had MRI findings of atrophy of the medial temporal lobe including the hippocampus. In the medial temporal lobe atrophy group, a personality change or general dementia remained even after the treatment was completed, and outcome in social functioning was poor. Medial temporal lobe atrophy may be a poor prognostic sign in general paresis.

Familial frontotemporal dementia with a P301L tau mutation in Japan.

We have reported the family line with frontotemporal dementia (FTD) in Japan. This family line has so far included four patients. Patient II-1 (man) had a 10 year history of slowly progressive personality and behavioral changes and died at the age of 56. His neuropathological examination showed severe atrophy of the bilateral frontal and temporal cortices with neuronal loss, gliosis and superficial spongiosis. Pick bodies were not found. The neuropathological diagnosis was atypical Pick's disease without Pick bodies or Pick-type in FTD. Patient III-2 is patient II-1's oldest daughter and was taken ill with personality change at the age of 52. She died at the age of 68. Patient III-4 is patient II-1's second daughter. Her onset with strange speech and behavior was at the age of 59. Patient III-5 is patient II-1's oldest son. He also had onset with personality change at the age of 54 and had the P301L mutation in tau. In all III generation cases CT/MRI revealed circumscribed frontotemporal atrophy. Patient III-5's PET/SPECT showed signs of hypoperfusion or hypometabolism in the bilateral frontotemporal areas. This is the first report of familial FTD with the P301L mutation in Japan.

Study of the association between the serotonin transporter gene regulatory region polymorphism and personality traits in a Japanese population.

Recently a relationship between serotonin transporter transcriptional control region (5-HTTLPR) polymorphism and anxiety related personality traits in Caucasians was reported. We performed PCR of DNAs from the blood for determining the 5-HTTLPR genotypes of 191 Japanese subjects, which were medical staff and students, and obtained Revised NEO Personality Inventory (NEO-PI-R) and the Temperament and Character Inventory (TCI) in 144 subjects. The association was analyzed by one-way ANOVA. The present study demonstrated that allelic frequency of 5-HTTLPR (s allele frequency was 0.785) in our subjects was considerably different from that in Caucasians. No significant differences were found in the anxiety-related personality traits among genotypes, while cooperativeness in TCI showed a significant difference among genotypes. The property of 5-HTTLPR may not be reflected directory on the personality inventories.