Neuroscience Insights最新文献

This article describes and analyzes various aspects related to the neurobiology of disorganized attachment (DA), which is associated with personality, eating, affective, dissociative, and addictive disorders. We included primary studies in humans, published in PubMed from 2000 to 2022. Eight genetic and one epigenetic study were considered. Three molecular studies describe possible roles of oxytocin and cortisol, seven neurophysiological studies investigated functional correlates, and five morphological studies describe anatomical changes. Findings in candidate genes involved in dopaminergic, serotonergic, and oxytonergic systems have not been able to be replicated in large-scale human studies. Alterations in the functioning of cortisol and oxytocin are preliminary. Neurophysiological studies show changes in subcortical structures (mainly in the hippocampus) and occipital, temporal, parietal, and insular cortices. Since there is a lack of robust evidence on the neurobiology of DA in humans, the possible inferences of these studies are preliminary, which restricts their translation to clinical parameters.

Repeated exposure to alcohol alters neuromolecular signaling that influences acute and long-lasting behaviors underlying Alcohol Use Disorder (AUD). Recent animal model research has implicated changes in the conserved JAK/STAT pathway, a signaling pathway classically associated with development and the innate immune system. How ethanol exposure impacts STAT signaling within neural cells is currently unclear. Here, we investigated the role of Drosophila Stat92E in ethanol-induced locomotion, signaling activity, and downstream transcriptional responses. Findings suggest that expressing Stat92E-RNAi causes enhanced ethanol-induced hyperactivity in flies previously exposed to ethanol. Furthermore, alternative splicing of Stat92E itself was detected after repeated ethanol exposure, although no changes were found in downstream transcriptional activity. This work adds to our growing understanding of altered neuromolecular signaling following ethanol exposure and suggests that STAT signaling may be a relevant target to consider for AUD treatment.

Chondroitin sulfate proteoglycans (CSPGs), one of the major extracellular matrix components of the glial scar that surrounds central nervous system (CNS) injuries, are known to inhibit the regeneration of neurons. This study investigated whether pleiotrophin (PTN), a growth factor upregulated during early CNS development, can overcome the inhibition mediated by CSPGs and promote the neurite outgrowth of neurons in vitro. The data showed that a CSPG matrix inhibited the outgrowth of neurites in primary cortical neuron cultures compared to a control matrix. PTN elicited a dose-dependent increase in the neurite outgrowth even in the presence of the growth inhibitory CSPG matrix, with optimal growth at 15 ng mL^-1 of PTN (114.8% of neuronal outgrowth relative to laminin control). The growth-promoting effect of PTN was blocked by inhibition of the receptor anaplastic lymphoma kinase (ALK) by alectinib in a dose-dependent manner. Neurite outgrowth in the presence of this CSPG matrix was induced by activation of the protein kinase B (AKT) pathway, a key downstream mediator of ALK activation. This study identified PTN as a dose-dependent regulator of neurite outgrowth in primary cortical neurons cultured in the presence of a CSPG matrix and identified ALK activation as a key driver of PTN-induced growth.

Music is an art form and cultural activity whose language, the sounds and silences, is organized in time with logic and sensitivity. Music as a whole is the result of an ancestral nonverbal and international mode of human expression and communication. The primitive and former mother-child bonding might be highly influenced and modulated by the music and singing with their babies. Musicality and music imply two different sides of the same coin, where the former is based on the human capacity to produce the latter. Some theories about evolution suggest music might have an adaptive advantage for humans in society. Historical examples of different styles in music point out that if any allusion or reminder about gender in music might happen most probably occurs in folk non always written pagan or secular music with lyrics or voice. This genre of music usually tells about traditional gender differences in jobs, habits, lifestyles, etc., and has a clear preference for male musicians, while on the contrary, classical music usually does not have a clear gender difference in meaning, and instruments are played by both. In this text, I explore and empirically describe, neuroanatomically or functionally, some examples of different genres of music and brain differences, related to music and dance. Three different genres of music (Classical music, Fado and Flamenco) are explored in an attempt to elucidate some reasons for possible gender differences.

Recovery of motor function after peripheral nerve injury requires treatment of the neuromuscular junction (NMJ), as well as the injured nerve and skeletal muscle. The purpose of this study was to examine the effects of ultrasound (US) stimulation on NMJ degeneration after denervation using a rat model of peroneal nerve transection. Twelve-week-old male Wistar rats were randomly assigned to 3 groups: US stimulation, sham stimulation, and intact. US or sham stimulation was performed on the left tibialis anterior (TA) muscle starting the day after peroneal nerve transection for 5 minutes daily under anesthesia. Four weeks later, the number and morphology of the motor endplates were analyzed to assess NMJ in the TA muscle. The endplates were classified as normal, partially fragmented, or fully fragmented for morphometric analysis. In addition, the number of terminal Schwann cells (tSCs) per endplate and percentage of endplates with tSCs (tSC retention percentage) were calculated to evaluate the effect of tSCs on NMJs. Our results showed that endplates degenerated 4 weeks after transection, with a decrease in the normal type and an increase in the fully fragmented type in both the US and sham groups compared to the intact group. Furthermore, the US group showed significant suppression of the normal type decrease and a fully fragmented type increase compared to the sham group. These results suggest that US stimulation inhibits endplate degeneration in denervated TA muscles. In contrast, the number of endplates and tSC and tSC retention percentages were not significantly different between the US and sham groups. Further investigations are required to determine the molecular mechanisms by which US stimulation suppresses degeneration.

This a Reply to the Letter to the Editor by Sipila, Jussi regarding our article titled: James LM, Georgopoulos AP. High Correlations Among Worldwide Prevalences of Dementias, Parkinson's Disease, Multiple Sclerosis, and Motor Neuron Diseases Indicate Common Causative Factors. Neurosci Insights. 2022 Aug 8;17:26331055221117598. doi: 10.1177/26331055221117598.

Mild traumatic brain injury (mTBI), a condition in which brain function is transiently disrupted by a mechanical force, is a major risk factor for developing Alzheimer's disease (AD) and other neurodegenerative conditions. In this commentary, we summarize recent findings in human neurons derived from induced pluripotent stem cells, detailing early neuronal events following mild injury that may seed future neurodegeneration. In particular, we discuss interlinked relationships between mTBI and several biological pathways hypothesized to underlie AD progression, including amyloidogenic cleavage of amyloid precursor protein (APP), impairment of axonal transport, and the development of APP-associated axonal swellings. We also describe the implications of these findings for future mechanistic and translational studies.

Alzheimer's disease (AD) is characterized by the aggregation and deposition of 2 amyloid proteins: amyloid β peptide (Aβ) and tau protein. Immunotherapies using anti-Aβ antibodies to promote the clearance of aggregated Aβ have recently been highlighted as a promising disease-modifying approach against AD. However, immunotherapy has still some problems, such as low efficiency of delivery into the brain and high costs. We have developed the "amyloid selective photo-oxygenation technology" as a comparable to immunotherapy for amyloids. The photo-oxygenation can artificially attach the oxygen atoms to specific amino acids in amyloid proteins using photocatalyst and light irradiation. We revealed that in vivo photo-oxygenation for living AD model mice reduced the aggregated Aβ in the brain. Moreover, we also showed that microglia were responsible for this promoted clearance of photo-oxygenated Aβ from the brain. These results indicated that our photo-oxygenation technology has the potential as a disease-modifying therapy against AD to promote the degradation of amyloids, resulting in being comparable to immunotherapy. Here, we introduce our technology and its effects in vivo that we showed previously in Ozawa et al., Brain, 2021, as well as a further improvement towards non-invasive in vivo photo-oxygenation described in another publication Nagashima et al., Sci. Adv., 2021, as expanded discussion.

While understudied, it is suspected that peripheral Aβ peptides affect Alzheimer's disease (AD)-associated pathological changes in the brain. The peripheral sink hypothesis postulates that the central and peripheral pools of Aβ co-exist in equilibrium. As such, cerebral amyloid levels may be modulated by intervening circulating Aβ. In this commentary, we discuss relevant literature supporting the potential role of peripheral Aβ in exacerbating brain amyloidosis in both humans and mouse models of AD. Moreover, we highlight the need to further understand the mechanisms by which circulating Aβ peptides may reach the brain and contribute to neuropathology. Finally, we discuss the implications of targeting peripheral Aβ as a therapeutic approach in treating AD.