The action of BDNF on GABAA currents changes from potentiating to suppressing during maturation of rat hippocampal CA1 pyramidal neurons

During the development of the hippocampus, the action of GABA shifts from depolarizing to hyperpolarizing, and brain-derived neurotrophic factor (BDNF) has important roles in GABAergic transmission. We demonstrate that BDNF (20 ng ml−1) rapidly and reversibly potentiates postsynaptic GABAA receptor-mediated currents (by 80.5 ± 14.3 %, n = 10) in hippocampal CA1 pyramidal neurons isolated from postnatal day (P)6 rats, using nystatin-perforated patch-clamp recordings. This potentiation is caused by an elevation of intracellular Ca2+ that occurs in response to the activation of Trk B receptor tyrosine kinase and phospholipase C-γ. The modulation of the GABAA responses by BDNF in hippocampal CA1 pyramidal neurons isolated from P10 rats was more diverse (from potentiating to inhibitory), and at P14, BDNF induced a long-lasting inhibition. In addition, Ca2+/calmodulin-dependent protein kinase 2 plays important roles in the potentiating, but not in the inhibitory effect, of BDNF on the GABAA responses. These results suggest that changes in the intracellular signalling pathway could contribute to the developmental shift of the actions of BDNF on inhibitory systems

Association between serum oxytocin levels and depressive state in community‐dwelling older adults: A cross‐sectional study

Abstract Aim Identifying peripheral biomarkers related to the prevention or modification of unhealthy mental conditions in older adults would be extremely beneficial. This study aimed to evaluate serum oxytocin levels in older adults living in a rural community and their association with cognitive function, anxiety, depressive state, and well‐being. Methods This survey was conducted between November 2016 and September 2017 in Kurokawa‐cho, Imari, Saga Prefecture, Japan, among people aged ≥65 years. Blood samples were collected from the participants for serum oxytocin level analysis, which was performed using peptide enzyme immunoassay. Participants underwent neuropsychological assessments, including the Mini‐Mental State Examination, Clinical Dementia Rating, Frontal Assessment Battery, State‐Trait Anxiety Inventory, 15‐item Geriatric Depression Scale, and 17‐item Philadelphia Geriatric Center Morale Scale. We examined the association between serum oxytocin levels and neuropsychological assessment results. Results Out of 94 participants, 25 were men and 69 were women, with mean ages of 78.24 ± 3.85 years and 78.10 ± 5.43 years, respectively. Serum oxytocin levels were negatively associated with 15‐item Geriatric Depression Scale scores. Additionally, nondepressive state/depressive state was classified by the 15‐item Geriatric Depression Scale (cut‐off 5/6). Logistic regression analysis showed that higher serum oxytocin levels tended to be associated with a less depressive state at that time. Conclusions Serum oxytocin levels may be associated with depressive state in adults aged ≥65 years

Additional file 1 of Association between cortisol and aging-related hippocampus volume changes in community-dwelling older adults: a 7-year follow-up study

Additional file 1: Supplementary Table 1. The 596 participants demographics at Timepoint 1. The 70 participants for the final analysis and the other 526 participants

Low-Grade Inflammation Is Associated with Apathy Indirectly via Deep White Matter Lesions in Community-Dwelling Older Adults: The Sefuri Study

Low-grade inflammation is implicated in the pathogenesis of atherosclerosis, metabolic syndrome, and apathy as a form of vascular depression. We analyzed the brain magnetic resonance imaging findings in 259 community-dwelling older adults (122 men and 137 women, with a mean age of 68.4 years). The serum concentrations of high-sensitivity C-reactive protein (hsCRP) were measured by a quantitative enzyme-linked immunosorbent assay. Logistic regression analysis revealed that the log10 hsCRP value and the presence of a metabolic syndrome were independently associated with confluent but not punctate deep white matter lesions (DWMLs). Path analysis based on structural equation modeling (SEM) indicated that the direct path from the log10 hsCRP to the DWMLs was significant (β = 0.119, p = 0.039). The direct paths from the metabolic syndrome to the log10 hsCRP and to the DWMLs were also significant. The direct path from the DWMLs to apathy (β = −0.165, p = 0.007) was significant, but the direct path from the log10 hsCRP to apathy was not significant. Inflammation (i.e., elevated serum hsCRP levels) was associated with DWMLs independent of common vascular risk factors, while DWMLs were associated with apathy. The present analysis with SEM revealed the more realistic scheme that low-grade inflammation was associated with apathy indirectly via DWMLs in community-dwelling older adults

Hyperbaric Oxygen Therapy for Carbon Monoxide-Induced Delayed Neuropsychiatric Sequelae: Case Report of Two Cases and Relevant Literature Review

We herein report two cases with carbon monoxide- (CO-) induced delayed neuropsychiatric sequelae (DNS) successfully treated with hyperbaric oxygen therapy (HBOT) in attempt suicide by charcoal burning. The two patients with CO-induced DNS were successfully treated with a total of more than 100 sessions of HBOT. Frontal assessment battery (FAB) was useful to examine the effectiveness of HBOT objectively. In the future study, a large-randomized trial is required to establish the efficacy of HBOT for the treatment of DNS

Donepezil suppresses intracellular Ca2+ mobilization through the PI3K pathway in rodent microglia

Abstract Background Microglia are resident innate immune cells which release many factors including proinflammatory cytokines or nitric oxide (NO) when they are activated in response to immunological stimuli. Pathophysiology of Alzheimer’s disease (AD) is related to the inflammatory responses mediated by microglia. Intracellular Ca2+ signaling is important for microglial functions such as release of NO and cytokines. In addition, alteration of intracellular Ca2+ signaling underlies the pathophysiology of AD, while it remains unclear how donepezil, an acetylcholinesterase inhibitor, affects intracellular Ca2+ mobilization in microglial cells. Methods We examined whether pretreatment with donepezil affects the intracellular Ca2+ mobilization using fura-2 imaging and tested the effects of donepezil on phagocytic activity by phagocytosis assay in rodent microglial cells. Results In this study, we observed that pretreatment with donepezil suppressed the TNFα-induced sustained intracellular Ca2+ elevation in both rat HAPI and mouse primary microglial cells. On the other hand, pretreatment with donepezil did not suppress the mRNA expression of both TNFR1 and TNFR2 in rodent microglia we used. Pretreatment with acetylcholine but not donepezil suppressed the TNFα-induced intracellular Ca2+ elevation through the nicotinic α7 receptors. In addition, sigma 1 receptors were not involved in the donepezil-induced suppression of the TNFα-mediated intracellular Ca2+ elevation. Pretreatment with donepezil suppressed the TNFα-induced intracellular Ca2+ elevation through the PI3K pathway in rodent microglial cells. Using DAF-2 imaging, we also found that pretreatment with donepezil suppressed the production of NO induced by TNFα treatment and the PI3K pathway could be important for the donepezil-induced suppression of NO production in rodent microglial cells. Finally, phagocytosis assay showed that pretreatment with donepezil promoted phagocytic activity of rodent microglial cells through the PI3K but not MAPK/ERK pathway. Conclusions These suggest that donepezil could directly modulate the microglial function through the PI3K pathway in the rodent brain, which might be important to understand the effect of donepezil in the brain

Neanderthal infant burial from the Dederiyeh cave in Syria.

A well-preserved Neanderthal infant burial was found in 1993 in the Dederiyeh Cave, Syria. The remains of this infant, about two years old, were located in the Mousterian deposit. Its position on the back, with arms extended and legs flexed, indicated an intentional burial. The burial brings new data on the association between Neanderthals and a Tabun В type of industry as well as on the geographic distribution Neanderthals in the Levant.Une sépulture bien préservée d'un enfant Néandertal fut trouvée en 1993 dans la grotte de Dederyeh en Syrie. Les restes de cet enfant, environ deux ans d'âge, ont été dégagés dans les dépôts moustériens. La position du dos, les bras étendus et les jambes fléchies indiquent une sépulture intentionelle. Cette sépulture apporte de nouvelles données sur l'association entre les Néandertals et l'industrie de type Tabun В ainsi que sur la distribution des Néandertals au Levant.Akazawa Takeru, Muhesen Sultan, Dodo Yukio, Kondo Osamu, Mizoguchi Yuji, Abe Yoshito, Nishiaki Yoshihiro A., Ohta Shoji, Oguchi Takashi, Haydal Jamal. Neanderthal infant burial from the Dederiyeh cave in Syria.. In: Paléorient, 1995, vol. 21, n°2. pp. 77-86