Involvement of BDNF receptor TrkB in spatial memory formation

The N-methyl-D-aspartate (NMDA) receptors are involved in long-term potentiation (LTP), and are phosphorylated by several tyrosine kinases including a Src-family tyrosine kinase Fyn. Brain-derived neurotrophic factor (BDNF) is a neurotrophin, which also enhances hippocampal synaptic transmission and efficacy by increasing NMDA receptor activity. Here, we show that Fyn is a key molecule linking the BDNF receptor TrkB with NMDA receptors, which play an important role in spatial memory formation in a radial arm maze. Spatial learning induced phosphorylation of TrkB, Fyn, and NR2B, but not NR2A, in the hippocampus. Fyn was coimmunoprecipitated with TrkB and NR2B, and this association was increased in well-trained rats compared with control animals. Continuous intracerebroventricular infusion of PP2, a tyrosine kinase inhibitor, in rats delayed memory acquisition in the radial arm maze, but PP2-treated animals reached the same level of learning as the controls. The phosphorylation of Fyn and NR2B, but not TrkB, was diminished by PP2 treatment. Our findings suggest the importance of interaction between BDNF/TrkB signaling and NMDA receptors for spatial memory in the hippocampus.     

Dopamine D1 receptors regulate protein synthesis-dependent long-term recognition memory via extracellular signal-regulated kinase 1/2 in the prefrontal cortex

Several lines of evidence suggest that extracellular signal-regulated kinase1/2 (ERK1/2) and dopaminergic system is involved in learning and memory. However, it remains to be determined if the dopaminergic system and ERK1/2 pathway contribute to cognitive function in the prefrontal cortex (PFC). The amount of phosphorylated ERK1/2 was increased in the PFC immediately after exposure to novel objects in the training session of the novel object recognition test. An inhibitor of ERK kinase impaired long-term recognition memory 24 h after the training although short-term memory tested 1 h after the training was not affected by the treatment. The dopamine D1 receptor agonist increased ERK1/2 phosphorylation in the PFC in vivo as well as in cortical neurons in vitro. Microinjection of the dopamine D1 receptor antagonist into the PFC impaired long-term recognition memory whereas the D2 receptor antagonist had no effect. Immunohistochemistry revealed that exposure to novel objects resulted in an increase in c-Fos expression in the PFC. Microinjection of the protein synthesis inhibitor anisomycin into the PFC impaired the long-term recognition memory. These results suggest that the activation of ERK1/2 following the stimulation of dopamine D1 receptors is necessary for the protein synthesis-dependent long-term retention of recognition memory in the PFC.     

Nociceptin and its metabolite attenuate U0126-induced memory impairment through a nociceptin opioid peptide (NOP) receptor-independent mechanism

Nociceptin binds to nociceptin opioid peptide (NOP) receptors. We reported that although high doses of nociceptin impaired memory function and that these effects were mediated via NOP receptors, low doses of nociceptin attenuated the memory impairment, and these attenuating effects were not mediated via NOP receptors. Even very low doses of nociceptin were biologically active and suggested a certain binding site for this peptide, but the mechanism underlying this attenuating effect has not yet been elucidated. In the present study, we investigated the effect of an intrahippocampal injection (i.h.) of nociceptin on memory impairment induced by U0126, a MEK inhibitor, and Rp-cAMPS, a PKA inhibitor in a step-down type passive avoidance test. U0126 (2.63 nmol/mouse, i.h.) impaired memory formation and training-dependent phosphorylation of ERK2 in the hippocampus. Co-administration of nociceptin (10 fmol/mouse) significantly attenuated memory impairment, while it did not attenuate the inhibition of training-dependent phosphorylation of ERK2 induced by U0126. On the other hand, nociceptin did not attenuate memory impairment induced by Rp-cAMPS (0.448 nmol/mouse, i.h.). Nociceptin (1 fmol/mouse) also attenuated U0126 (5.26 nmol/mouse)-induced memory impairment in NOP receptor knockout mice. Nociceptin was reported to metabolize into fragments (1–13) and (14–17) in vivo, which showed pharmacological activities without affecting NOP receptors. Our findings showed that nociceptin (14–17) (1 fmol/mouse) also attenuated U0126-induced memory impairment, while nociceptin (1–13) (0.1–10 fmol/mouse) did not attenuate memory impairment. These results suggest a novel action site or mechanism for the attenuating effects of nociceptin and its metabolite, and the sequence of nociceptin (14–17) is a critical structure.     

Depression and somatic symptoms in Japanese and American college students: Negative mood regulation expectancies as a personality correlate

This study clarified contradictory findings regarding whether depression and somatic symptoms are associated more strongly with each other in non‐Western countries than in Western countries, by examining the relationships of the two variables with negative mood regulation expectancies (NMRE). NMRE are beliefs about one's ability to improve one's negative moods. Participants were 155 Japanese and 176 American undergraduates. They completed self‐report measures of NMRE, coping, depression and somatic symptoms. Results showed that depression significantly correlated with somatic symptoms for both men and women in both countries, and there was no cultural difference in the relationship between depression and somatic symptoms. The relationships of depression and somatic symptoms with NMRE did not differ between cultures. NMRE explained variance in depression in both countries but variance in somatic symptoms only for women in both countries. The relationship of NMRE with depression and somatic symptoms paralleled that between depression and somatic symptoms for both cultures. These results were consistent with the previous literature that found no difference between cultures. Results support the cross‐cultural validity of measuring NMRE in the context of coping and distress.     

A second Leonardo da Vinci?

We describe a young woman who suddenly began mirror writing with her right hand and has not reverted to normal writing for more than 6 years, although she writes normally with her left hand. She is ambidextrous, although she had previously used only her right hand for writing and drawing. Since it is much easier for her to use right-handed mirror writing, she uses her left hand only for writing meant to be read by others and her right hand for all other writing. Her hobbies are sculpture and painting, and her chief complaint is migraine accompanied by sensory and perceptive disturbances.     

The Effect of Perfectionism and Acculturative Stress on Levels of Depression Experienced by East Asian International Students

This study examined relationships among acculturative stress, grade point average satisfaction, maladaptive perfectionism, and depression in 52 East Asian international students and 126 North American students. Results indicated that a combined effect of perfectionism and acculturative stress accounted for more than 30% of the variance related to depression. Implications include the importance of attending to perfectionism and acculturative stress for improving the overall well‐being of East Asian international students. Este estudio examinó las relaciones entre el estrés aculturativo, la satisfacción con el promedio de calificaciones, el perfeccionismo inadaptado y la depresión en 52 estudiantes internacionales del este asiático y 126 estudiantes norteamericanos. Los resultados indicaron que el efecto combinado del perfeccionismo y el estrés aculturativo representó más del 30% de la varianza relacionada con la depresión. Las implicaciones incluyen la importancia de prestar atención a los niveles de perfeccionismo y estrés aculturativo para mejorar el bienestar general de los estudiantes internacionales del este asiático.